2163PathwaySarcosine Oncometabolite Pathway Sarcosine is a compound derived from the amino acid glycine and is involved in both its synthesis and degradation, and is an intermediate in the metabolism of choline to glycine. In cases of prostate cancer, the cancer cells seem to produce higher levels of sarcosine. Elevated levels of sarcosine found in the urine of patients with prostate cancer, and it has been suggested that these elevated levels are responsible for the development of the cancer.
This pathway begins with choline’s transport into the mitochondrial matrix via xolute carrier family protein 44 A1 and the choline transporter-like protein 2. Once in the matrix, choline is oxidized to betaine aldehyde by choline dehydrogenase, and in the process reduces an acceptor. Betaine aldehyde is then converted to betaine by the addition of a water molecule by alpha-aminoadipic semialdehyde dehydrogenase. Following this, betaine is transported out of the mitochondria by an unknown transporter, where it then reacts with homocysteine to form dimethylglycine and L-methionine in a reaction catalyzed by betaine-homocysteine S-methyltransferase 1. The dimethylglycine is then transported back into the mitochondrial matrix by another unknown transporter, where it can react with tetrahydrofolate to form sarcosine and 5-methyltetrahydrofolic acid in a reaction catalyzed by dimethylglycine dehydrogenase. In at least some cases of prostate cancer cells, the SARDH gene is mutated, which encodes the sarcosine dehydrogenase protein. This can lead to an increase of sarcosine in the cells, as sarcosine dehydrogenase typically converts sarcosine to glycine, which is then converted to and from L-serine by serine hydroxymethyltransferase. With a non-functional or less functional enzyme, sarcosine levels will be increased, and serine and glycine levels will be reduced.
A separate set of reactions outside of the mitochondria begins with the L-methionine produced by betaine—homocysteine S-methyltransferase 1, which is then converted to S-adenosylmethionine by a complex consisting of S-adenosylmethionine synthase and methionine adenosyltransferase. S-adenosylmethionine then reacts with glycine reversibly to form S-adenosylhomocysteine, as well as sarcosine. The expression of the gene encoding glycine N-methyltransferase, GNMT, can also be elevated in cancer tissues, leading to an increased concentration of sarcosine outside of the mitochondria as well.
DiseasePW002387CenterPathwayVisualizationContext267528504550#000099PathwayVisualization21462163Sarcosine Oncometabolite Pathway Sarcosine is a compound derived from the amino acid glycine and is involved in both its synthesis and degradation, and is an intermediate in the metabolism of choline to glycine. In cases of prostate cancer, the cancer cells seem to produce higher levels of sarcosine. Elevated levels of sarcosine found in the urine of patients with prostate cancer, and it has been suggested that these elevated levels are responsible for the development of the cancer.
This pathway begins with choline’s transport into the mitochondrial matrix via xolute carrier family protein 44 A1 and the choline transporter-like protein 2. Once in the matrix, choline is oxidized to betaine aldehyde by choline dehydrogenase, and in the process reduces an acceptor. Betaine aldehyde is then converted to betaine by the addition of a water molecule by alpha-aminoadipic semialdehyde dehydrogenase. Following this, betaine is transported out of the mitochondria by an unknown transporter, where it then reacts with homocysteine to form dimethylglycine and L-methionine in a reaction catalyzed by betaine-homocysteine S-methyltransferase 1. The dimethylglycine is then transported back into the mitochondrial matrix by another unknown transporter, where it can react with tetrahydrofolate to form sarcosine and 5-methyltetrahydrofolic acid in a reaction catalyzed by dimethylglycine dehydrogenase. In at least some cases of prostate cancer cells, the SARDH gene is mutated, which encodes the sarcosine dehydrogenase protein. This can lead to an increase of sarcosine in the cells, as sarcosine dehydrogenase typically converts sarcosine to glycine, which is then converted to and from L-serine by serine hydroxymethyltransferase. With a non-functional or less functional enzyme, sarcosine levels will be increased, and serine and glycine levels will be reduced.
A separate set of reactions outside of the mitochondria begins with the L-methionine produced by betaine—homocysteine S-methyltransferase 1, which is then converted to S-adenosylmethionine by a complex consisting of S-adenosylmethionine synthase and methionine adenosyltransferase. S-adenosylmethionine then reacts with glycine reversibly to form S-adenosylhomocysteine, as well as sarcosine. The expression of the gene encoding glycine N-methyltransferase, GNMT, can also be elevated in cancer tissues, leading to an increased concentration of sarcosine outside of the mitochondria as well.
Disease1498923633921Khan AP, Rajendiran TM, Ateeq B, Asangani IA, Athanikar JN, Yocum AK, Mehra R, Siddiqui J, Palapattu G, Wei JT, Michailidis G, Sreekumar A, Chinnaiyan AM: The role of sarcosine metabolism in prostate cancer progression. Neoplasia. 2013 May;15(5):491-501.2163Pathway499023797698de Vogel S, Ulvik A, Meyer K, Ueland PM, Nygard O, Vollset SE, Tell GS, Gregory JF 3rd, Tretli S, Bjorge T: Sarcosine and other metabolites along the choline oxidation pathway in relation to prostate cancer--a large nested case-control study within the JANUS cohort in Norway. Int J Cancer. 2014 Jan 1;134(1):197-206. doi: 10.1002/ijc.28347. Epub 2013 Jul 27.2163Pathway1CellCL:00000005HepatocyteCL:00001824CardiomyocyteCL:00007463NeuronCL:00005407Epithelial CellCL:00000662Platelet CL:00002338Beta cellCL:00006396MyocyteCL:000018710Glial cellCL:000012518ErythrocyteCL:000023228MacrophageCL:00002351Homo sapiens9606EukaryoteHuman17Rattus norvegicus10116EukaryoteRat4Arabidopsis thaliana3702EukaryoteThale cress12Mus musculus10090EukaryoteMouse5Bos taurus9913EukaryoteCattle6Caenorhabditis elegans6239EukaryoteRoundworm10Drosophila melanogaster7227EukaryoteFruit fly3Escherichia coli562Prokaryote24Solanum lycopersicum4081EukaryoteTomato18Saccharomyces cerevisiae4932EukaryoteYeast21Xenopus laevis8355EukaryoteAfrican clawed frog49Bathymodiolus platifrons220390EukaryoteDeep sea mussel23Pseudomonas aeruginosa287Prokaryote60Nitzschia sp.0001EukaryoteNitzschia42Bacteria2ProkaryoteBacteria19Schizosaccharomyces pombe4896Eukaryote25Escherichia coli (strain K12)83333Prokaryote29Saccharomyces cerevisiae (strain ATCC 204508 / S288c)559292EukaryoteBaker's yeast51Picea sitchensis3332EukaryoteSitka spruce196Homo1924EukaryoteHuman157Acinetobacter baumannii 107673Prokaryote280Bacteroides fragilis55247009Prokaryote2MitochondrionGO:000573911Extracellular SpaceGO:00056155CytoplasmGO:000573710Cell MembraneGO:00058861CytosolGO:00058294PeroxisomeGO:00057777Endoplasmic Reticulum MembraneGO:00057896LysosomeGO:00057643Mitochondrial MatrixGO:000575912Mitochondrial Inner MembraneGO:000574316Lysosomal LumenGO:004320213Endoplasmic ReticulumGO:000578324Mitochondrial Intermembrane SpaceGO:000575814Mitochondrial Outer MembraneGO:000574120Endoplasmic Reticulum LumenGO:000578831Periplasmic SpaceGO:000562035ChloroplastGO:000950734Plant-Type VacuoleGO:000032539Mitochondrial membraneGO:003196625Golgi ApparatusGO:000579418Melanosome MembraneGO:003316221SynapseGO:004520215NucleusGO:000563436MembraneGO:001602053Endoplasmic Reticulum BodyGO:001016840PeriplasmGO:004259727Peroxisome MembraneGO:000577832Inner MembraneGO:007025817NucleoplasmGO:000565419Sarcoplasmic ReticulumGO:001652926Golgi Apparatus MembraneGO:000013937Basolateral cell membraneGO:001632349Nuclear EnvelopeGO:000563556Basal Cell MembraneGO:000992538Apical cell membraneGO:00163241LiverBTO:00007597294Adrenal MedullaBTO:000004971825IntestineBTO:000064828StomachBTO:0001307155267Nervous SystemBTO:00014848Blood VesselBTO:0001102741111HeartBTO:000056273106KidneyBTO:00006717182Endothelium BTO:000039318PancreasBTO:00009889MuscleBTO:0000887141185cardiocyteBTO:00015393Sympathetic Nervous 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is a basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. Choline is now considered to be an essential vitamin. While humans can synthesize small amounts (by converting phosphatidylethanolamine to phosphatidylcholine), it must be consumed in the diet to maintain health. Required levels are between 425 mg/day (female) and 550 mg/day (male). Milk, eggs, liver, and peanuts are especially rich in choline. Most choline is found in phospholipids, namely phosphatidylcholine or lecithin. Choline can be oxidized to form betaine, which is a methyl source for many reactions (i.e. conversion of homocysteine into methionine). Lack of sufficient amounts of choline in the diet can lead to a fatty liver condition and general liver damage. This arises from the lack of VLDL, which is necessary to transport fats away from the liver. Choline deficiency also leads to elevated serum levels of alanine amino transferase and is associated with increased incidence of liver cancer.62-49-7C0011430515354CPD-563299DB00122C[N+](C)(C)CCOC5H14NOInChI=1S/C5H14NO/c1-6(2,3)4-5-7/h7H,4-5H2,1-3H3/q+1OEYIOHPDSNJKLS-UHFFFAOYSA-N(2-hydroxyethyl)trimethylazanium104.1708104.107539075-1.591choline11FDB000710(2-hydroxyethyl)trimethyl ammonium;(2-hydroxyethyl)trimethylammonium;(beta-hydroxyethyl)trimethylammonium;2-hydroxy-n,n,n-trimethyl-ethanaminium;2-hydroxy-n,n,n-trimethylethanaminium;Bilineurine;Biocolina;Biocoline;Choline;Choline cation;Choline ion;Cholinum;Hepacholine;Hormocline;Lipotril;N,n,n-trimethylethanol-ammonium;N,n,n-trimethylethanolammonium;Neocolina;Paresan;N-trimethylethanolamine;TrimethylethanolaminePW_C000065Choline56235641556581497145612119561913768497121851511219716412278226153392153804977614112776191147853011579972132799803319482912494859383113285388115541118115753398120489407120497409121306405123876376125987478126471481127440209128040206967βine aldehydeHMDB0001252Betaine aldehyde is an intermediate in the metabolism of glycine, serine and threonine. The human aldehyde dehydrogenase (EC 1.2.1.3) facilitates the conversion of betaine aldehyde to glycine betaine. Betaine aldehyde is a substrate for Choline dehydrogenase (mitochondrial). (PMID: 12467448, 7646513).7418-61-3C0057624915710BETAINE_ALDEHYDE244DB04401C[N+](C)(C)CC=OC5H12NOInChI=1S/C5H12NO/c1-6(2,3)4-5-7/h5H,4H2,1-3H3/q+1SXKNCCSPZDCRFD-UHFFFAOYSA-Ntrimethyl(2-oxoethyl)azanium102.1549102.091889011-2.170betaine aldehyde11FDB022513(formylmethyl)trimethylammonium;(formylmethyl)trimethyl-ammonium;Btl;Betaine aldehyde;Glycine betaine aldehyde;N,n,n-trimethyl-2-oxo ethanaminium;N,n,n-trimethyl-2-oxo-ethanaminium;Trimethyl(formylmethyl)ammoniumPW_C000967BinAld56081898355891351228122677604111120469122964FADHMDB0001248FAD, also known as flavitan or adeflavin, belongs to the class of organic compounds known as flavin nucleotides. These are nucleotides containing a flavin moiety. Flavin is a compound that contains the tricyclic isoalloxazine ring system, which bears 2 oxo groups at the 2- and 4-positions. FAD is a drug which is used to treat eye diseases caused by vitamin b2 deficiency, such as keratitis and blepharitis. FAD is slightly soluble (in water) and a moderately acidic compound (based on its pKa). FAD has been found in human liver and muscle tissues, and has also been detected in multiple biofluids, such as feces and blood. Within the cell, FAD is primarily located in the cytoplasm, mitochondria, endoplasmic reticulum and peroxisome. FAD exists in all living organisms, ranging from bacteria to humans. In humans, FAD is involved in the risedronate action pathway, the ibandronate action pathway, the valine, leucine and isoleucine degradation pathway, and the pyrimidine metabolism pathway. FAD is also involved in several metabolic disorders, some of which include the oncogenic action OF L-2-hydroxyglutarate in hydroxygluaricaciduria pathway, gaba-transaminase deficiency, 4-hydroxybutyric aciduria/succinic semialdehyde dehydrogenase deficiency, and the saccharopinuria/hyperlysinemia II pathway. FAD is a condensation product of riboflavin and adenosine diphosphate. The coenzyme of various aerobic dehydrogenases, e.g., D-amino acid oxidase and L-amino acid oxidase. (Lehninger, Principles of Biochemistry, 1982, p972).146-14-5C0001664397516238FAD559059DB03147CC1=CC2=C(C=C1C)N(C[C@H](O)[C@H](O)[C@H](O)COP(O)(=O)OP(O)(=O)OC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=NC3=C1N=CN=C3N)C1=NC(=O)NC(=O)C1=N2C27H33N9O15P2InChI=1S/C27H33N9O15P2/c1-10-3-12-13(4-11(10)2)35(24-18(32-12)25(42)34-27(43)33-24)5-14(37)19(39)15(38)6-48-52(44,45)51-53(46,47)49-7-16-20(40)21(41)26(50-16)36-9-31-17-22(28)29-8-30-23(17)36/h3-4,8-9,14-16,19-21,26,37-41H,5-7H2,1-2H3,(H,44,45)(H,46,47)(H2,28,29,30)(H,34,42,43)/t14-,15+,16+,19-,20+,21+,26+/m0/s1VWWQXMAJTJZDQX-UYBVJOGSSA-N{[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}[({[(2R,3S,4S)-5-{7,8-dimethyl-2,4-dioxo-2H,3H,4H,10H-benzo[g]pteridin-10-yl}-2,3,4-trihydroxypentyl]oxy}(hydroxy)phosphoryl)oxy]phosphinic acid785.5497785.157134455-2.279flavine-adenine dinucleotide0-3FDB0225111h-purin-6-amine flavin dinucleotide;1h-purin-6-amine flavine dinucleotide;Adenine-flavin dinucleotide;Adenine-flavine dinucleotide;Adenine-riboflavin dinuceotide;Adenine-riboflavin dinucleotide;Adenine-riboflavine dinucleotide;Fad;Flamitajin b;Flanin f;Flavin adenine dinucleotide;Flavin adenine dinucleotide oxidized;Flavin-adenine dinucleotide;Flavine adenosine diphosphate;Flavine-adenine dinucleotide;Flavitan;Flaziren;Isoalloxazine-adenine dinucleotide;Riboflavin 5'-adenosine diphosphate;Riboflavin-adenine dinucleotide;Riboflavine-adenine dinucleotide;AdeflavinPW_C000964FAD9991145186819232164253176282882518840211881414894216122916224921335825362237232646023646883147411347581048816526810352851025335111549612655111275613118603015560541566082161611616263901647517864991796666107703916371752057321213746522274872239076224118182161188721511899211122962251232824912443151125192271259522612710291127202921302930113041302436233187708029377126133771521347750111377507112775181157754133477615132777263377805432978375345789303317922233679272358800123688003436980714119119958406119999384120051408120107407120432405120453122120490124121278429121298418121417382121489383122748120122776121122802374122823443123066376123087135123166448123849464123868454123976399124047398125348479125378480125429482125474481125697297125979489126107299126277484126891501126920391126968502126987207127011206127310209127432506127602388127840389140790185140799186721NADHMDB0000902NAD (or Nicotinamide adenine dinucleotide) is used extensively in glycolysis and the citric acid cycle of cellular respiration. The reducing potential stored in NADH can be converted to ATP through the electron transport chain or used for anabolic metabolism. ATP "energy" is necessary for an organism to live. Green plants obtain ATP through photosynthesis, while other organisms obtain it by cellular respiration. (wikipedia). Nicotinamide adenine dinucleotide is a A coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). (Dorland, 27th ed).53-84-9C00003589315846NAD5682NC(=O)C1=C[N+](=CC=C1)[C@@H]1O[C@H](COP([O-])(=O)OP(O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)N2C=NC3=C2N=CN=C3N)[C@@H](O)[C@H]1OC21H27N7O14P2InChI=1S/C21H27N7O14P2/c22-17-12-19(25-7-24-17)28(8-26-12)21-16(32)14(30)11(41-21)6-39-44(36,37)42-43(34,35)38-5-10-13(29)15(31)20(40-10)27-3-1-2-9(4-27)18(23)33/h1-4,7-8,10-11,13-16,20-21,29-32H,5-6H2,(H5-,22,23,24,25,33,34,35,36,37)/t10-,11-,13-,14-,15-,16-,20-,21-/m1/s1BAWFJGJZGIEFAR-NNYOXOHSSA-N1-[(2R,3R,4S,5R)-5-({[({[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphono}oxy)(hydroxy)phosphoryl]oxy}methyl)-3,4-dihydroxyoxolan-2-yl]-3-(C-hydroxycarbonimidoyl)-1lambda5-pyridin-1-ylium663.4251663.109121631-2.5281-[(2R,3R,4S,5R)-5-{[({[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphono}oxy(hydroxy)phosphoryl)oxy]methyl}-3,4-dihydroxyoxolan-2-yl]-3-(C-hydroxycarbonimidoyl)-1lambda5-pyridin-1-ylium0-1FDB0223093-carbamoyl-1-d-ribofuranosylpyridinium hydroxide 5'-ester with adenosine 5'-pyrophosphate;3-carbamoyl-1-beta-d-ribofuranosylpyridinium hydroxide 5'-ester with adenosine 5'-pyrophosphate inner salt;3-carbamoyl-1-beta-delta-ribofuranosylpyridinium hydroxide 5'-ester with adenosine 5'-pyrophosphate inner salt;3-carbamoyl-1-delta-ribofuranosylpyridinium hydroxide 5'-ester with adenosine 5'-pyrophosphate;Adenine-nicotinamide dinucleotide;Co-i;Codehydrase i;Codehydrogenase i;Coenzyme i;Cozymase;Cozymase i;Diphosphopyridine nucleotide;Diphosphopyridine nucleotide oxidized;Endopride;Nad trihydrate;Nad-oxidized;Nicotinamide adenine dinucleotide;Nicotinamide adenine dinucleotide oxidized;Nicotinamide dinucleotide;Nicotineamide adenine dinucleotide;Oxidized diphosphopyridine nucleotide;Pyridine nucleotide diphosphate;[(3s,2r,4r,5r)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl {[(3s,2r,4r,5r)-5-(3-carbamoylpyridyl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxyphosphoryl) hydrogen phosphate;[adenylate-32-p]-nad;Beta-diphosphopyridine nucleotide;Beta-nad;Beta-nicotinamide adenine dinucleotide;Beta-nicotinamide adenine dinucleotide trihydrate;Dpn;Nad;Nad+;Nadide;B-nad;β-nadPW_C000721NAD140415033538651101114211344312735146654222949277917283529310794807184813184819284902649603151679552381035334111536011254691235482125559013556101185696100573810858271415912147594215160241556072157607616163851646917867721176890160701218870971637174205719720674051987459222824122683592259085224118192161232224913006298130183001325622342404322426193157710413277120133772091347737033177650336776673347770233277709130779151137798334778406356800063688069011993825124110552388112750166112853941199291221199524061201714071208344191209844081211594251212421261212594291218173831226143841227421201231304471231411361234194551235493741237314601238124431238294641243703981251871211253192971253424791255304811258062991258254901259244821265154951267654801268855011272785071273835021280893901283603911284283951407571851420WaterHMDB0002111Water is a chemical substance that is essential to all known forms of life. It appears colorless to the naked eye in small quantities, though it is actually slightly blue in color. It covers 71% of Earth's surface. Current estimates suggest that there are 1.4 billion cubic kilometers (330 million m3) of it available on Earth, and it exists in many forms. It appears mostly in the oceans (saltwater) and polar ice caps, but it is also present as clouds, rain water, rivers, freshwater aquifers, lakes, and sea ice. Water in these bodies perpetually moves through a cycle of evaporation, precipitation, and runoff to the sea. Clean water is essential to human life. In many parts of the world, it is in short supply. From a biological standpoint, water has many distinct properties that are critical for the proliferation of life that set it apart from other substances. It carries out this role by allowing organic compounds to react in ways that ultimately allow replication. All known forms of life depend on water. Water is vital both as a solvent in which many of the body's solutes dissolve and as an essential part of many metabolic processes within the body. Metabolism is the sum total of anabolism and catabolism. In anabolism, water is removed from molecules (through energy requiring enzymatic chemical reactions) in order to grow larger molecules (e.g. starches, triglycerides and proteins for storage of fuels and information). In catabolism, water is used to break bonds in order to generate smaller molecules (e.g. glucose, fatty acids and amino acids to be used for fuels for energy use or other purposes). Water is thus essential and central to these metabolic processes. Water is also central to photosynthesis and respiration. Photosynthetic cells use the sun's energy to split off water's hydrogen from oxygen. Hydrogen is combined with CO2 (absorbed from air or water) to form glucose and release oxygen. All living cells use such fuels and oxidize the hydrogen and carbon to capture the sun's energy and reform water and CO2 in the process (cellular respiration). Water is also central to acid-base neutrality and enzyme function. An acid, a hydrogen ion (H+, that is, a proton) donor, can be neutralized by a base, a proton acceptor such as hydroxide ion (OH-) to form water. Water is considered to be neutral, with a pH (the negative log of the hydrogen ion concentration) of 7. Acids have pH values less than 7 while bases have values greater than 7. Stomach acid (HCl) is useful to digestion. However, its corrosive effect on the esophagus during reflux can temporarily be neutralized by ingestion of a base such as aluminum hydroxide to produce the neutral molecules water and the salt aluminum chloride. Human biochemistry that involves enzymes usually performs optimally around a biologically neutral pH of 7.4. (Wikipedia).7732-18-5C0000196215377937OH2OInChI=1S/H2O/h1H2XLYOFNOQVPJJNP-UHFFFAOYSA-Nwater18.015318.0105646861water00FDB013390Dihydrogen oxide;Steam;[oh2];Acqua;Agua;Aqua;Bound water;Dihydridooxygen;Eau;H2o;Hoh;Hydrogen hydroxide;WasserPW_C001420H2O558949109513941513162144811352615624286521069120770338231883821094311377491465541590432018242532222678602727462778172805293143703164723634614598364727374941935030275156751959752141005227945236103529710553191115343113535511254021105470123548312554921265507127553413055371145541129559113556081185622108569165759140577810158411435853146587710758909559101475940151603215560591576087161612316361331596215162181666477178650718066001526713117684018868881607162205718120771932067211211722821372382147243215729519873502167388210740121274672227492224750019075881708201225823722684141629265261185027711922164120112811221328512250286122642871232724912520227126326512693290127052911271529213007298130193001302530113037302132612231332729415340308423273154269531843691322769142937701925377102132771311337721513477378331773973327747133377516115775363347762833677722337777593417781634377982347780713297823535278242353782703567911336080014368800393708059122880656119938303839479438411055739011063939111584439811987923211991512211996340612000840712004640812011312412036541212043040512043840912060641512079441412115842512124042912135112112138141912160743412211838212238443612275312012279737412280444312301244612306437612307213712313144712314213612316244812323145112338445012373046012381046412394045512416546912467039912493847112494547212530529712535347912538648112542448212548029912568248312570747812574548712605449012623849512627348412676448012689650112696350212701738812717720812719920912722750412750650712757651512783638912808239512817651314067479014067583414075518530βineHMDB0000043Betaine (or N,N,N-trimethylglycine) was named after its discovery in sugar beet (Beta vulgaris) in the 19th century. It is a small N-trimethylated amino acid, existing in zwitterionic form at neutral pH. It is now often called glycine betaine to distinguish it from other betaines that are widely distributed in microorganisms, plants, and animals. Many naturally occurring betaines serve as organic osmolytes, substances synthesized or taken up from the environment by cells for protection against osmotic stress, drought, high salinity, or high temperature. Intracellular accumulation of betaines permits water retention in cells, thus protecting from the effects of dehydration (Wikipedia). Betaine functions as a methyl donor in that it carries and donates methyl functional groups to facilitate necessary chemical processes. In particular, it methylates homocysteine to methionine, also producing N,N-dimethylglycine. The donation of methyl groups is important to proper liver function, cellular replication, and detoxification reactions. Betaine also plays a role in the manufacture of carnitine and serves to protect the kidneys from damage. Betaine comes from either the diet or by the oxidation of choline. Betaine insufficiency is associated with metabolic syndrome, lipid disorders, and diabetes, and may have a role in vascular and other diseases (PMID: 20346934). Betaine is important in development, from the pre-implantation embryo to infancy. Betaine is also widely regarded as an anti-oxidant. Betaine has been shown to have an inhibitory effect on NO release in activated microglial cells and may be an effective therapeutic component to control neurological disorders (PMID: 22801281). As a drug, betaine hydrochloride has been used as a source of hydrochloric acid in the treatment of hypochlorhydria. Betaine has also been used in the treatment of liver disorders, for hyperkalemia, for homocystinuria, and for gastrointestinal disturbances (Martindale, The Extra Pharmacopoeia, 30th Ed, p1341).107-43-7C0071924717750BETAINE242C[N+](C)(C)CC([O-])=OC5H11NO2InChI=1S/C5H11NO2/c1-6(2,3)4-5(7)8/h4H2,1-3H3KWIUHFFTVRNATP-UHFFFAOYSA-N2-(trimethylazaniumyl)acetate117.1463117.078978601-1.960(trimethylammonio)acetate00FDB009020(carboxymethyl)trimethylammonium hydroxide inner salt;(trimethylammonio)acetate;1-carboxy-n,n,n-trimethyl-methanaminium;1-carboxy-n,n,n-trimethyl-methanaminium hydroxide;1-carboxy-n,n,n-trimethylmethanaminium inner salt;Abromine;Aminocoat;Betafin;Betafin bcr;Betafin bp;Betaine;Cystadane;Ektasolve ee;Finnstim;Glycine betaine;Glycocoll betaine;Glycylbetaine;Greenstim;Loramine amb 13;Loramine amb-13;Lycine;N,n,n-trimethylglycine;Oxyneurine;Rubrine c;Trimethylaminoacetate;Trimethylaminoacetic acid;Trimethylbetaine glycine;Trimethylglycine;Trimethylglycocoll;A-earleine;Alpha-earleine;(trimethylammoniumyl)acetate;2-n,n,n-trimethylammonio acetate;Acidol;Bet;N,n,n-trimethylammonioacetate;Trimethylammonioacetate;(trimethylammoniumyl)acetic acid;2-(trimethylazaniumyl)acetic acid;2-n,n,n-trimethylammonio acetic acid;N,n,n-trimethylammonioacetic acid;Trimethylammonioacetic acidPW_C000030βine5581555981899334702559213556181376850712282226776051117761811478104132783151121204701221204964091221501241222944071247021181248471191263092991264614811278713881280312061144NADHHMDB0001487NADH is the reduced form of NAD+, and NAD+ is the oxidized form of NADH, A coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). It forms NADP with the addition of a phosphate group to the 2' position of the adenosyl nucleotide through an ester linkage.(Dorland, 27th ed).58-68-4C0000443915316908NADH388299DB00157NC(=O)C1=CN(C=CC1)[C@@H]1O[C@H](CO[P@](O)(=O)O[P@](O)(=O)OC[C@H]2O[C@H]([C@H](O)[C@@H]2O)N2C=NC3=C(N)N=CN=C23)[C@@H](O)[C@H]1OC21H29N7O14P2InChI=1S/C21H29N7O14P2/c22-17-12-19(25-7-24-17)28(8-26-12)21-16(32)14(30)11(41-21)6-39-44(36,37)42-43(34,35)38-5-10-13(29)15(31)20(40-10)27-3-1-2-9(4-27)18(23)33/h1,3-4,7-8,10-11,13-16,20-21,29-32H,2,5-6H2,(H2,23,33)(H,34,35)(H,36,37)(H2,22,24,25)/t10-,11-,13-,14-,15-,16-,20-,21-/m1/s1BOPGDPNILDQYTO-NNYOXOHSSA-N[({[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]({[(2R,3S,4R,5R)-5-(3-carbamoyl-1,4-dihydropyridin-1-yl)-3,4-dihydroxyoxolan-2-yl]methoxy})phosphinic acid665.441665.124771695-2.358NADH0-2FDB0226491,4-dihydronicotinamide adenine dinucleotide;Dpnh;Dihydrocodehydrogenase i;Dihydrocozymase;Dihydronicotinamide adenine dinucleotide;Dihydronicotinamide mononucleotide;Enada;Nadh;Nadh2;Reduced codehydrogenase i;Reduced diphosphopyridine nucleotide;Reduced nicotinamide adenine diphosphate;Reduced nicotinamide-adenine dinucleotide;B-dpnh;B-nadh;Beta-dpnh;Beta-nadh;Nicotinamide adenine dinucleotide (reduced);Reduced nicotinamide adenine dinucleotidePW_C001144NADH14341533490864810111521275514695422304927811728362931099480618481218482128490464959315169955240103533211153581125466123547912555931355698100573710858291415915147594515160271556079161638716472178677111768931607011188709916371722057195206746222282442268360225908622411809198118212161232024913003298130153001325522342403322426183157710713277123133772081347737133177651336776683347770033277707130779171137798634780009368806911199382212411054938811285494115838118119955406120172407120378122120986408121162425121244126121693429121818383122616384122745120123127447123138136123551374123734460123814443124242464124371398125189121125345479125531481125762297125808299125926482126516495126767480126888501127385502128090390128362391128429395140759185590HomocysteineHMDB0000742Homocysteine is a sulfur-containing amino acid that arises during methionine metabolism. Although its concentration in plasma is only about 10 micromolar (uM), even moderate hyperhomocysteinemia is associated with increased incidence of cardiovascular disease and Alzheimer's disease. Elevations in plasma homocysteine are commonly found as a result of vitamin deficiencies, polymorphisms of enzymes of methionine metabolism, and renal disease. Pyridoxal, folic acid, riboflavin, and Vitamin B(12) are all required for methionine metabolism, and deficiency of each of these vitamins result in elevated plasma homocysteine. A polymorphism of methylenetetrahydrofolate reductase (C677T), which is quite common in most populations with a homozygosity rate of 10-15 %, is associated with moderate hyperhomocysteinemia, especially in the context of marginal folate intake. Plasma homocysteine is inversely related to plasma creatinine in patients with renal disease. This is due to an impairment in homocysteine removal in renal disease. The role of these factors, and of modifiable lifestyle factors, in affecting methionine metabolism and in determining plasma homocysteine levels is discussed. Homocysteine is an independent cardiovascular disease (CVD) risk factor modifiable by nutrition and possibly exercise. Homocysteine was first identified as an important biological compound in 1932 and linked with human disease in 1962 when elevated urinary homocysteine levels were found in children with mental retardation. This condition, called homocysteinuria, was later associated with premature occlusive CVD, even in children. These observations led to research investigating the relationship of elevated homocysteine levels and CVD in a wide variety of populations including middle age and elderly men and women with and without traditional risk factors for CVD. (PMID 17136938, 15630149).454-29-5C053304979197817230HOMO-CYS757N[C@@H](CCS)C(O)=OC4H9NO2SInChI=1S/C4H9NO2S/c5-3(1-2-8)4(6)7/h3,8H,1-2,5H2,(H,6,7)/t3-/m0/s1FFFHZYDWPBMWHY-VKHMYHEASA-N(2S)-2-amino-4-sulfanylbutanoic acid135.185135.035399227-0.963L-homocysteine00DBMET00508FDB001491(+-)-homocysteine;(s)-2-amino-4-mercapto-butanoate;(s)-2-amino-4-mercapto-butanoic acid;2-amino-4-mercapto-butanoate;2-amino-4-mercapto-butanoic acid;2-amino-4-mercapto-butyric acid;2-amino-4-mercapto-dl-butyrate;2-amino-4-mercapto-dl-butyric acid;2-amino-4-mercaptobutyric acid;2-amino-4-sulfanylbutanoate;2-amino-4-sulfanylbutanoic acid;D,l-homocysteine;Dl-2-amino-4-mercaptobutyric acid;Dl-2-amino-4-mercapto-butyric acid;Dl-homocysteine;Dl-homocysteine (free base);Hcy;Homo-cys;Homocysteine;L-2-amino-4-mercapto-butyric acid;L-homocysteine;Usaf b-12;2-amino-4-mercaptobutyratePW_C000590Hcys56681824255951358264225776071117810513212047612212215112412470311812579329712631029912724820512787238862DimethylglycineHMDB0000092Dimethylglycine (DMG) is an amino acid derivative found in the cells of all plants and animals and can be obtained in the diet in small amounts from grains and meat. The human body produces DMG when metabolizing choline into Glycine. Dimethylglycine that is not metabolized in the liver is transported by the circulatory system to body tissue. Dimethylglycine was popular with Russian athletes and cosmonauts owing to its reputed ability to increase endurance and reduce fatigue. DMG is also a byproduct of homocysteine metabolism. Homocysteine and betaine are converted to methionine and N, N-dimethylglycine by betaine-homocysteine methyltransferase.1118-68-9C0102667317724DIMETHYL-GLYCINE653DB02083CN(C)CC(O)=OC4H9NO2InChI=1S/C4H9NO2/c1-5(2)3-4(6)7/h3H2,1-2H3,(H,6,7)FFDGPVCHZBVARC-UHFFFAOYSA-N2-(dimethylamino)acetic acid103.1198103.0633285370.961dimethylglycine00FDB021893(dimethylamino)acetate;(dimethylamino)acetic acid;2-(dimethylamino)acetate;2-(dimethylamino)acetic acid;Dimethylglycine;N,n-dimethylaminoacetate;N,n-dimethylaminoacetic acid;N,n-dimethylglycine;N-methylsarcosine n,n-dimethyl-glycinePW_C000062DMglyc567819002255435596135776081117807911278316132120477122122125407122295124124677119124848118126282481126462299127845206128032388548L-MethionineHMDB0000696Methionine is an essential amino acid (there are 9 essential amino acids) required for normal growth and development of humans, other mammals, and avian species. In addition to being a substrate for protein synthesis, it is an intermediate in transmethylation reactions, serving as the major methyl group donor in vivo, including the methyl groups for DNA and RNA intermediates. Methionine is a methyl acceptor for 5-methyltetrahydrofolate-homocysteine methyltransferase (methionine synthase), the only reaction that allows for the recycling of this form of folate, and is also a methyl acceptor for the catabolism of betaine. Methionine is the metabolic precursor for cysteine. Only the sulfur atom from methionine is transferred to cysteine; the carbon skeleton of cysteine is donated by serine (PMID: 16702340). There is a general consensus concerning normal sulfur amino acid (SAA) requirements. WHO recommendations amount to 13 mg/kg per 24 h in healthy adults. This amount is roughly doubled in artificial nutrition regimens. In disease or after trauma, requirements may be altered for methionine, cysteine, and taurine. Although in specific cases of congenital enzyme deficiency, prematurity, or diminished liver function, hypermethioninemia or hyperhomocysteinemia may occur, SAA supplementation can be considered safe in amounts exceeding 2-3 times the minimum recommended daily intake. Apart from some very specific indications (e.g. acetaminophen poisoning) the usefulness of SAA supplementation is not yet established (PMID: 16702341). Methionine is known to exacerbate psychopathological symptoms in schizophrenic patients, but there is no evidence of similar effects in healthy subjects. The role of methionine as a precursor of homocysteine is the most notable cause for concern. Acute doses of methionine can lead to acute increases in plasma homocysteine, which can be used as an index of the susceptibility to cardiovascular disease. Sufficiently high doses of methionine can actually result in death. Longer-term studies in adults have indicated no adverse consequences of moderate fluctuations in dietary methionine intake, but intakes higher than 5 times the normal amount resulted in elevated homocysteine levels. These effects of methionine on homocysteine and vascular function are moderated by supplements of vitamins B-6, B-12, C, and folic acid (PMID: 16702346). When present in sufficiently high levels, methionine can act as an atherogen and a metabotoxin. An atherogen is a compound that when present at chronically high levels causes atherosclerosis and cardiovascular disease. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Chronically high levels of methionine are associated with at least ten inborn errors of metabolism, including cystathionine beta-synthase deficiency, glycine N-methyltransferase deficiency, homocystinuria, tyrosinemia, galactosemia, homocystinuria-megaloblastic anemia due to defects in cobalamin metabolism, methionine adenosyltransferase deficiency, methylenetetrahydrofolate reductase deficiency, and S-adenosylhomocysteine (SAH) hydrolase deficiency. Chronically elevated levels of methionine in infants can lead to intellectual disability and other neurological problems, delays in motor skills, sluggishness, muscle weakness, and liver problems. Many individuals with these metabolic disorders tend to develop cardiovascular disease later in life. Studies on feeding rodents high levels of methionine have shown that methionine promotes atherosclerotic plaques independently of homocysteine levels (PMID: 26647293). A similar study in Finnish men showed the same effect (PMID: 16487911).63-68-3C00073613716643MET5907DB00134CSCC[C@H](N)C(O)=OC5H11NO2SInChI=1S/C5H11NO2S/c1-9-3-2-4(6)5(7)8/h4H,2-3,6H2,1H3,(H,7,8)/t4-/m0/s1FFEARJCKVFRZRR-BYPYZUCNSA-N(2S)-2-amino-4-(methylsulfanyl)butanoic acid149.211149.051049291-0.802L-methionine00DBMET00506FDB012683(2s)-2-amino-4-(methylsulfanyl)butanoate;(2s)-2-amino-4-(methylsulfanyl)butanoic acid;(l)-methionine;(s)-(+)-methionine;(s)-2-amino-4-(methylthio)butanoate;(s)-2-amino-4-(methylthio)butanoic acid;(s)-2-amino-4-(methylthio)-butanoate;(s)-2-amino-4-(methylthio)-butanoic acid;(s)-2-amino-4-(methylthio)butyric acid;(s)-methionine;2-amino-4-(methylthio)butyrate;2-amino-4-(methylthio)butyric acid;2-amino-4-methylthiobutanoate;2-amino-4-methylthiobutanoic acid;A-amino-g-methylmercaptobutyrate;A-amino-g-methylmercaptobutyric acid;Acimethin;Cymethion;G-methylthio-a-aminobutyrate;G-methylthio-a-aminobutyric acid;H-met-h;H-met-oh;L(-)-amino-alpha-amino-alpha-aminobutyric acid;L(-)-amino-gamma-methylthiobutyric acid;L-(-)-methionine;L-2-amino-4-(methylthio)butyric acid;L-2-amino-4-methylthiobutyric acid;L-methionin;L-methionine;L-methioninum;L-a-amino-g-methylthiobutyrate;L-a-amino-g-methylthiobutyric acid;L-alpha-amino-gamma-methylmercaptobutyric acid;L-alpha-amino-gamma-methylthiobutyrate;L-alpha-amino-gamma-methylthiobutyric acid;L-gamma-methylthio-alpha-aminobutyric acid;Liquimeth;Met;Mepron;Methilanin;Methionine;Methioninum;Metionina;Neo-methidin;Poly-l-methionine;Polymethionine;S-methionine;S-methyl-l-homocysteine;Toxin war;Alpha-amino-alpha-aminobutyric acid;Alpha-amino-gamma-methylmercaptobutyrate;Alpha-amino-gamma-methylmercaptobutyric acid;Gamma-methylthio-alpha-aminobutyrate;Gamma-methylthio-alpha-aminobutyric acid;M;(2s)-2-amino-4-(methylsulphanyl)butanoate;(2s)-2-amino-4-(methylsulphanyl)butanoic acid;(s)-2-amino-4-(methylthio)butyrate;L-a-amino-g-methylmercaptobutyrate;L-a-amino-g-methylmercaptobutyric acid;L-alpha-amino-gamma-methylmercaptobutyrate;L-α-amino-γ-methylmercaptobutyrate;L-α-amino-γ-methylmercaptobutyric acidPW_C000548Met56881825255971355680107568110858751058267151120332224255031542565318426933207698522477609111781061321204781221221521241247041181258582971263112991273202051278733881005Zinc (II) ionHMDB0001303Zinc is an essential element, necessary for sustaining all life.Physiologically, it exists as an ion in the body. It is estimated that 3000 of the hundreds of thousands of proteins in the human body contain zinc prosthetic groups. In addition, there are over a dozen types of cells in the human body that secrete zinc ions, and the roles of these secreted zinc signals in medicine and health are now being actively studied. Intriguingly, brain cells in the mammalian forebrain are one type of cell that secretes zinc, along with its other neuronal messenger substances. Cells in the salivary gland, prostate, immune system and intestine are other types that secrete zinc. Obtaining a sufficient zinc intake during pregnancy and in young children is a problem, especially among those who cannot afford a good and varied diet. Brain development is stunted by zinc deficiency in utero and in youth. Zinc is an activator of certain enzymes, such as carbonic anhydrase. Carbonic anhydrase is important in the transport of carbon dioxide in vertebrate blood. Even though zinc is an essential requirement for a healthy body, too much zinc can be harmful. Excessive absorption of zinc can also suppress copper and iron absorption. The free zinc ion in solution is highly toxic to plants, invertebrates, and even vertebrate fish. The Free Ion Activity Model (FIAM) is well-established in the literature, and shows that just micromolar amounts of the free ion kills some organisms.23713-49-7C000383205129105ZN%2b229723DB01593[Zn++]ZnInChI=1S/Zn/q+2PTFCDOFLOPIGGS-UHFFFAOYSA-Nzinc(2+) ion65.40963.9291465780zinc(2+) ion22FDB003729Zinc;Zinc ion;Dietary zinc;Zinc cation;Zinc, ion (zn2+);Zn(ii);Zn(2+);Zn2+PW_C001005Zinc1323841188271165291529575130446831202931477054101175425103543411854591205560132558513355981357449166117871981246622612724290133211517696722577401111775801147792933680400112002012412003540612006012212044140912125742912307513712382746412539829912541347912543829712568548312693838812695350112697620512718020810795-Methyltetrahydrofolic acidHMDB00013965 methyltetrahydrofolic acid (5-MTHF) is the most biologically active form of the B-vitamin known as folic acid, also known generically as folate. 5-MTHF functions, in concert with vitamin B12, as a methyl-group donor involved in the conversion of the amino acid homocysteine to methionine. Methyl (CH3) group donation is vital to many bodily processes, including serotonin, melatonin, and DNA synthesis. Therapeutically, 5-MTHF is instrumental in reducing homocysteine levels, preventing neural tube defects, and improving vascular endothelial function. Research on folate supplementation suggests it plays a key role in preventing cervical dysplasia and protecting against neoplasia in ulcerative colitis. Folic acid also shows promise as part of a nutritional protocol to treat vitiligo, and may reduce inflammation of the gingiva. Furthermore, certain neurological, cognitive, and psychiatric presentations may be secondary to folate deficiency. Such presentations include depression, peripheral neuropathy, myelopathy, restless legs syndrome, insomnia, dementia, forgetfulness, irritability, endogenous depression, organic psychosis, and schizophrenia-like syndromes. After ingestion, the process of conversion of folic acid to the metabolically active coenzyme forms is relatively complex. Synthesis of the active forms of folic acid requires several enzymes, adequate liver and intestinal function, and adequate supplies of riboflavin (B2), niacin (B3), pyridoxine (B6), zinc, vitamin C, and serine. After formation of the coenzyme forms of the vitamin in the liver, these metabolically active compounds are secreted into the small intestine with bile (the folate enterohepatic cycle), where they are reabsorbed and distributed to tissues throughout the body. Human pharmacokinetic studies indicate folic acid has high bioavailability, with large oral doses of folic acid substantially raising plasma levels in healthy subjects in a time and dose dependent manner. Red blood cells (RBCs) appear to be the storage depot for folic acid, as RBC levels remain elevated for periods in excess of 40 days following discontinuation of supplementation. Folic acid is poorly transported to the brain and rapidly cleared from the central nervous system. The primary methods of elimination of absorbed folic acid are fecal (through bile) and urinary. Despite the biochemical complexity of this process, evidence suggests oral supplementation with folic acid increases the body's pool of 5-MTHF in healthy individuals. However, enzyme defects, mal-absorption, digestive system pathology, and liver disease can result in impaired ability to activate folic acid. In fact, some individuals have a severe congenital deficiency of the enzyme Methyl tetrahydrofolate reductase (5-MTHFR), which is needed to convert folic acid to 5-MTHF. Milder forms of this enzyme defect likely interact with dietary folate status to determine risk for some disease conditions. In individuals with a genetic defect of this enzyme (whether mild or severe), supplementation with 5- MTHF might be preferable to folic acid supplementation. (PMID: 17176169).134-35-0C00440439234156415-METHYL-THF388371CN1C(CNC2=CC=C(C=C2)C(=O)N[C@H](CCC(O)=O)C(O)=O)CNC2=C1C(=O)NC(N)=N2C20H25N7O6InChI=1S/C20H25N7O6/c1-27-12(9-23-16-15(27)18(31)26-20(21)25-16)8-22-11-4-2-10(3-5-11)17(30)24-13(19(32)33)6-7-14(28)29/h2-5,12-13,22H,6-9H2,1H3,(H,24,30)(H,28,29)(H,32,33)(H4,21,23,25,26,31)/t12?,13-/m1/s1ZNOVTXRBGFNYRX-ZGTCLIOFSA-N(2R)-2-[(4-{[(2-amino-5-methyl-4-oxo-3,4,5,6,7,8-hexahydropteridin-6-yl)methyl]amino}phenyl)formamido]pentanedioic acid459.4558459.186631567-3.127(2R)-2-[(4-{[(2-amino-5-methyl-4-oxo-3,6,7,8-tetrahydropteridin-6-yl)methyl]amino}phenyl)formamido]pentanedioic acid0-2DBMET00528FDB0226005-methyl tetrahydrofolate;5-methyl-5,6,7,8-tetrahydrofolate;5-methyl-tetrahydrofolate;5-methyltetrahydrofolate;5-methyltetrahydropteroylglutamate;Methyl folate;Methyl-tetrahydrofolate;N( 5)-methyltetrahydrofolate;N-(4-(((2-amino-1,4,5,6,7,8-hexahydro-5-methyl-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-l-glutamate;N-(4-(((2-amino-1,4,5,6,7,8-hexahydro-5-methyl-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-l-glutamic acid;N-(5-methyl-5,6,7,8-tetrahydropteroyl)-l-glutamate;N-(5-methyl-5,6,7,8-tetrahydropteroyl)-l-glutamic acid;N5-methyl-tetrahydrofolate;N5-methyl-tetrahydrofolic acid;N5-methyltetrahydrofolate;N5-methyltetrahydropteroyl mono-l-glutamate;[(6s)-5-methyl-5,6,7,8-tetrahydropteroyl]glutamatePW_C0010795-MTHFa570818212533311156001357173205782961321204811221222781241248321181257632971264442991280133881221Tetrahydrofolic acidHMDB0001846Tetrahydrofolate is a soluble coenzyme (vitamin B9) that is synthesized de novo by plants and microorganisms, and absorbed from the diet by animals. It is composed of three distinct parts: a pterin ring, a p-ABA (p-aminobenzoic acid) and a polyglutamate chain with a number of residues varying between 1 and 8. Only the tetra-reduced form of the molecule serves as a coenzyme for C1 transfer reactions. In biological systems, the C1-units exist under various oxidation states and the different tetrahydrofolate derivatives constitute a family of related molecules named indistinctly under the generic term folate. (PMID 16042593). Folate is important for cells and tissues that rapidly divide. Cancer cells divide rapidly, and drugs that interfere with folate metabolism are used to treat cancer. Methotrexate is a drug often used to treat cancer because it inhibits the production of the active form, tetrahydrofolate. Unfortunately, methotrexate can be toxic, producing side effects such as inflammation in the digestive tract that make it difficult to eat normally. -- Wikipedia; Signs of folic acid deficiency are often subtle. Diarrhea, loss of appetite, and weight loss can occur. Additional signs are weakness, sore tongue, headaches, heart palpitations, irritability, and behavioral disorders. Women with folate deficiency who become pregnant are more likely to give birth to low birth weight and premature infants, and infants with neural tube defects. In adults, anemia is a sign of advanced folate deficiency. In infants and children, folate deficiency can slow growth rate. Some of these symptoms can also result from a variety of medical conditions other than folate deficiency. It is important to have a physician evaluate these symptoms so that appropriate medical care can be given. -- Wikipedia; Folinic acid is a form of folate that can help 'rescue' or reverse the toxic effects of methotrexate. Folinic acid is not the same as folic acid. Folic acid supplements have little established role in cancer chemotherapy. There have been cases of severe adverse effects of accidental substitution of folic acid for folinic acid in patients receiving methotrexate cancer chemotherapy. It is important for anyone receiving methotrexate to follow medical advice on the use of folic or folinic acid supplements. -- Wikipedia. Low concentrations of folate, vitamin B12, or vitamin B6 may increase the level of homocysteine, an amino acid normally found in blood. There is evidence that an elevated homocysteine level is an independent risk factor for heart disease and stroke. The evidence suggests that high levels of homocysteine may damage coronary arteries or make it easier for blood clotting cells called platelets to clump together and form a clot. However, there is currently no evidence available to suggest that lowering homocysteine with vitamins will reduce your risk of heart disease. Clinical intervention trials are needed to determine whether supplementation with folic acid, vitamin B12 or vitamin B6 can lower your risk of developing coronary heart disease. -- Wikipedia.135-16-0C001011378185720506THF18714427DB00116NC1=NC(=O)C2=C(NC[C@H](CNC3=CC=C(C=C3)C(=O)NC(CCC(O)=O)C(O)=O)N2)N1C19H23N7O6InChI=1S/C19H23N7O6/c20-19-25-15-14(17(30)26-19)23-11(8-22-15)7-21-10-3-1-9(2-4-10)16(29)24-12(18(31)32)5-6-13(27)28/h1-4,11-12,21,23H,5-8H2,(H,24,29)(H,27,28)(H,31,32)(H4,20,22,25,26,30)/t11-,12?/m0/s1MSTNYGQPCMXVAQ-PXYINDEMSA-N2-{[4-({[(6S)-4-hydroxy-2-imino-1,2,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)phenyl]formamido}pentanedioic acid445.4292445.170981503-3.2292-{[4-({[(6S)-4-hydroxy-2-imino-5,6,7,8-tetrahydro-1H-pteridin-6-yl]methyl}amino)phenyl]formamido}pentanedioic acid0-1FDB022705(6s)-tetrahydrofolate;(6s)-tetrahydrofolic acid;5,6,7,8-tetrahydrofolate;5,6,7,8-tetrahydrofolic acid;Tetra-h-folate;Tetrahydrafolate;Tetrahydrofolate;Tetrahydrofolic acid;Tetrahydropteroyl mono-l-glutamate;TetrahydropteroylglutamatePW_C001221THFA4484571897531809253071115347112560113557861086009147706618871512057185206758316311797198426403157733613378118132120352406120482122120696407122166124123001120123301119124718118125673479125749297125771481126324299127168501127886388414Adenosine triphosphateHMDB0000538Adenosine triphosphate (ATP) is a nucleotide consisting of a purine base (adenine) attached to the first carbon atom of ribose (a pentose sugar). Three phosphate groups are esterified at the fifth carbon atom of the ribose. ATP is incorporated into nucleic acids by polymerases in the processes of DNA replication and transcription. ATP contributes to cellular energy charge and participates in overall energy balance, maintaining cellular homeostasis. ATP can act as an extracellular signaling molecule via interactions with specific purinergic receptors to mediate a wide variety of processes as diverse as neurotransmission, inflammation, apoptosis, and bone remodelling. Extracellular ATP and its metabolite adenosine have also been shown to exert a variety of effects on nearly every cell type in human skin, and ATP seems to play a direct role in triggering skin inflammatory, regenerative, and fibrotic responses to mechanical injury, an indirect role in melanocyte proliferation and apoptosis, and a complex role in Langerhans cell-directed adaptive immunity. During exercise, intracellular homeostasis depends on the matching of adenosine triphosphate (ATP) supply and ATP demand. Metabolites play a useful role in communicating the extent of ATP demand to the metabolic supply pathways. Effects as different as proliferation or differentiation, chemotaxis, release of cytokines or lysosomal constituents, and generation of reactive oxygen or nitrogen species are elicited upon stimulation of blood cells with extracellular ATP. The increased concentration of adenosine triphosphate (ATP) in erythrocytes from patients with chronic renal failure (CRF) has been observed in many studies but the mechanism leading to these abnormalities still is controversial. (PMID: 15490415, 15129319, 14707763, 14696970, 11157473).56-65-5C00002595715422ATP5742DB00171NC1=NC=NC2=C1N=CN2[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1OC10H16N5O13P3InChI=1S/C10H16N5O13P3/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(17)6(16)4(26-10)1-25-30(21,22)28-31(23,24)27-29(18,19)20/h2-4,6-7,10,16-17H,1H2,(H,21,22)(H,23,24)(H2,11,12,13)(H2,18,19,20)/t4-,6-,7-,10-/m1/s1ZKHQWZAMYRWXGA-KQYNXXCUSA-N({[({[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl}oxy)phosphonic acid507.181506.995745159-2.057adenosine triphosphate0-3FDB0218135'-(tetrahydrogen triphosphate) adenosine;5'-atp;Atp;Adenosine 5'-triphosphate;Adenosine 5'-triphosphorate;Adenosine 5'-triphosphoric acid;Adenosine triphosphate;Adenylpyrophosphorate;Adenylpyrophosphoric acid;Adephos;Adetol;Adynol;Atipi;Atriphos;Cardenosine;Fosfobion;Glucobasin;Myotriphos;Phosphobion;Striadyne;Triadenyl;Triphosphaden;Triphosphoric acid adenosine ester;Adenosine-5'-triphosphate;H4atp;Adenosine triphosphoric acid;Adenosine-5'-triphosphoric acidPW_C000414ATP92214608266164142247813733327995934399763210518211210214649215614216058240559243427272646281229302966316372361661361751439923447431476891486454503289503526515575205975215100525010452911015313111534611253901035406117543011854431205542129555613255691335603135562110858461435854146587610758971475924151604815561091616230166649317868391886870160697619971572057184206720921072252137229211729819873022167390217740821874321637481222749919081862251184727711903170120102811203916412178285125782261269129013264223153273084232631542621322426943187702825377218134772333297746833377632336780373327804135078168128782143517824035378411335784941157885013078865331789193348002836880046184806741198562919482612411323494113282388116280109119914122119992406120154407120245382120362412121246429121392123121397433121471408121974410122065125122079383122083405122402422122444435122919399123009446123816464123951447123956468124029374124527444124616136124630398124634376124943472124972375125011470125304297125371479125392299125515481125595484126123485126220300126234495126240478126547491126596499126913501127123389127731516127781395127796390127801209128119508128167517140770891921S-AdenosylmethionineHMDB0001185S-Adenosylmethionine (CAS: 29908-03-0), also known as SAM or AdoMet, is a physiologic methyl radical donor involved in enzymatic transmethylation reactions and present in all living organisms. It possesses anti-inflammatory activity and has been used in the treatment of chronic liver disease (From Merck, 11th ed). S-Adenosylmethionine is a natural substance present in the cells of the body. It plays a crucial biochemical role by donating a one-carbon methyl group in a process called transmethylation. S-Adenosylmethionine, formed from the reaction of L-methionine and adenosine triphosphate catalyzed by the enzyme S-adenosylmethionine synthetase, is the methyl-group donor in the biosynthesis of both DNA and RNA nucleic acids, phospholipids, proteins, epinephrine, melatonin, creatine, and other molecules.485-80-3C000192476216515414S-ADENOSYLMETHIONINE31983DB00118C[S+](CC[C@H](N)C(O)=O)C[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=NC2=C1N=CN=C2NC15H23N6O5SInChI=1S/C15H22N6O5S/c1-27(3-2-7(16)15(24)25)4-8-10(22)11(23)14(26-8)21-6-20-9-12(17)18-5-19-13(9)21/h5-8,10-11,14,22-23H,2-4,16H2,1H3,(H2-,17,18,19,24,25)/p+1/t7-,8+,10+,11+,14+,27?/m0/s1MEFKEPWMEQBLKI-AIRLBKTGSA-O[(3S)-3-amino-3-carboxypropyl]({[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl})methylsulfanium399.445399.145063566-2.565SAMe11FDB022473(3s)-5'-[(3-amino-3-carboxypropyl)methylsulfonio]-5'-deoxyadenosine;2-s-adenosyl-l-methionine;5'-deoxyadenosine-5'-l-methionine disulfate ditosylate;Active methionine;Ademetionine;Adenosylmethionine;Adomet;Donamet;L-s-adenosylmethionine;S-(5'-adenosyl)-l-methionine;S-(5'-deoxyadenosin-5'-yl)-l-methionine;S-adenosyl methionine;S-adenosyl-l-methionine disulfate tosylate;S-adenosyl-l-methionine;S-adenosyl-methionine;S-adenosylmethionine;5'-deoxyadenosine-5'-l-methionine disulphate ditosylate;S-adenosyl-l-methionine disulphate tosylate;(3s)-5'-[(3-amino-3-carboxypropyl)methylsulfonio]-5'-deoxyadenosine, inner salt;[1-(adenin-9-yl)-1,5-dideoxy-beta-d-ribofuranos-5-yl][(3s)-3-amino-3-carboxypropyl](methyl)sulfonium;Acylcarnitine;Sam;SamePW_C000921SAMe5198633307042012203188027206624681105023505604135713616375402107544213763216082661519235195118741981203122212358225152932491534518153633097689729376899164769842247748811177731338777723417809913278303351783353467915511279961361808612294830382948333861132863891132883971155433991155464011203931221205374131209394071210521241222824351231714491235051191236161181248364701258592971258794811263042991264474991273212051273402061275953881280175171104PhosphateHMDB0001429Phosphate is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry, biogeochemistry and ecology. Phosphate (Pi) is an essential component of life. In biological systems, phosphorus is found as a free phosphate ion in solution and is called inorganic phosphate, to distinguish it from phosphates bound in various phosphate esters. Inorganic phosphate is generally denoted Pi and at physiological (neutral) pH primarily consists of a mixture of HPO<sup>2-</sup><sub>4</sub> and H<sub>2</sub>PO<sup>-</sup><sub>4</sub> ions. phosphates are most commonly found in the form of adenosine phosphates, (AMP, ADP and ATP) and in DNA and RNA and can be released by the hydrolysis of ATP or ADP. Similar reactions exist for the other nucleoside diphosphates and triphosphates. Phosphoanhydride bonds in ADP and ATP, or other nucleoside diphosphates and triphosphates, contain high amounts of energy which give them their vital role in all living organisms. Phosphate must be actively transported into cells against its electrochemical gradient. In vertebrates, two unrelated families of Na+-dependent Pi transporters carry out this task. Remarkably, the two families transport different Pi species: whereas type II Na+/Pi cotransporters (SCL34) prefer divalent HPO4(2), type III Na+/Pi cotransporters (SLC20) transport monovalent H2PO4. The SCL34 family comprises both electrogenic and electroneutral members that are expressed in various epithelia and other polarized cells. Through regulated activity in apical membranes of the gut and kidney, they maintain body Pi homeostasis, and in salivary and mammary glands, liver, and testes they play a role in modulating the Pi content of luminal fluids. Phosphate levels in the blood play an important role in hormone signaling and in bone homeostasis. In classical endocrine regulation, low serum phosphate induces the renal production of the seco-steroid hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3).This active metabolite of vitamin D acts to restore circulating mineral (i.e. phosphate and calcium) levels by increasing absorption in the intestine, reabsorption in the kidney, and mobilization of calcium and phosphate from bone. Thus, chronic renal failure is associated with hyperparathyroidism, which in turn contributes to osteomalacia (softening of the bones). Another complication of chronic renal failure is hyperphosphatemia (low levels of phosphate in the blood). Hyperphosphatemia (excess levels of phosphate in the blood) is a prevalent condition in kidney dialysis patients and is associated with increased risk of mortality. Hypophosphatemia (hungry bone syndrome) has been associated to postoperative electrolyte aberrations and after parathyroidectomy. (PMID: 17581921, 11169009, 11039261, 9159312, 17625581)Fibroblast growth factor 23 (FGF-23) has recently been recognized as a key mediator of phosphate homeostasis, its most notable effect being promotion of phosphate excretion. FGF-23 was discovered to be involved in diseases such as autosomal dominant hypophosphatemic rickets, X-linked hypophosphatemia, and tumor-induced osteomalacia in which phosphate wasting was coupled to inappropriately low levels of 1,25(OH)2D3. FGF-23 is regulated by dietary phosphate in humans. In particular it was found that phosphate restriction decreased FGF-23, and phosphate loading increased FGF-23.14265-44-2C00009106118367CPD-85871032OP(O)(O)=OH3O4PInChI=1S/H3O4P/c1-5(2,3)4/h(H3,1,2,3,4)NBIIXXVUZAFLBC-UHFFFAOYSA-Nphosphoric acid97.995297.9768950963phosphoric acid0-2DBMET00532FDB022617Nfb orthophosphate;O-phosphoric acid;Ortho-phosphate;Orthophosphate (po43-);Orthophosphate(3-);Phosphate;Phosphate (po43-);Phosphate anion(3-);Phosphate ion (po43-);Phosphate ion(3-);Phosphate trianion;Phosphate(3-);Phosphoric acid ion(3-);Pi;[po4](3-);Orthophosphate;Phosphate ion;Po4(3-);Phosphoric acid;Orthophosphoric acid;Phosphoric acid ionPW_C001104Pi2448488145818188312980317631417674925001027294727374631292931667236366138512342492244753150312751587520797521610053171115351112538110354471205543129557313356051355625108569365848143585514659111475941151604015561001616294107648717866911016714117684218868891607161205718920672122117306198738921074022127436163747522281962258258227101182411013425711748132117611151177321311904170119271641201428112728290132632233481917422553044235031542435318436923227701825377194293772171347794033677966130780483327805732978245353786693318002236889279308938313839479638411055839011064039111323594115845398116206109119982406120069122120699407121057124121216125121268429121352121121409123121423382121852405123304119123621118123786136123838464123968447123981399124405376124948472125362479125446297125774481125954299126221478126594300126604298126723484126904501127413388127783209128166395128177513128315389170PyrophosphateHMDB0000250The anion, the salts, and the esters of pyrophosphoric acid are called pyrophosphates. The pyrophosphate anion is abbreviated PPi and is formed by the hydrolysis of ATP into AMP in cells. This hydrolysis is called pyrophosphorolysis. The pyrophosphate anion has the structure P2O74-, and is an acid anhydride of phosphate. It is unstable in aqueous solution and rapidly hydrolyzes into inorganic phosphate. Pyrophosphate is an osteotoxin (arrests bone development) and an arthritogen (promotes arthritis). It is also a metabotoxin (an endogenously produced metabolite that causes adverse health affects at chronically high levels). Chronically high levels of pyrophosphate are associated with hypophosphatasia. Hypophosphatasia (also called deficiency of alkaline phosphatase or phosphoethanolaminuria) is a rare, and sometimes fatal, metabolic bone disease. Hypophosphatasia is associated with a molecular defect in the gene encoding tissue non-specific alkaline phosphatase (TNSALP). TNSALP is an enzyme that is tethered to the outer surface of osteoblasts and chondrocytes. TNSALP hydrolyzes several substances, including inorganic pyrophosphate (PPi) and pyridoxal 5'-phosphate (PLP), a major form of vitamin B6. When TSNALP is low, inorganic pyrophosphate (PPi) accumulates outside of cells and inhibits the formation of hydroxyapatite, one of the main components of bone, causing rickets in infants and children and osteomalacia (soft bones) in adults. Vitamin B6 must be dephosphorylated by TNSALP before it can cross the cell membrane. Vitamin B6 deficiency in the brain impairs synthesis of neurotransmitters which can cause seizures. In some cases, a build-up of calcium pyrophosphate dihydrate crystals in the joints can cause pseudogout.14000-31-8C0001364410218361PPI559142DB04160OP(O)(=O)OP(O)(O)=OH4O7P2InChI=1S/H4O7P2/c1-8(2,3)7-9(4,5)6/h(H2,1,2,3)(H2,4,5,6)XPPKVPWEQAFLFU-UHFFFAOYSA-N(phosphonooxy)phosphonic acid177.9751177.9432255064pyrophosphoric acid0-3FDB021918(4-)diphosphoric acid ion;(p2o74-)diphosphate;Diphosphate;Diphosphoric acid;Ppi;Pyrometaphosphate;Pyrophosphate;Pyrophosphate tetraanion;Pyrophosphate(4-) ion;[o3popo3](4-);Diphosphat;P2o7(4-);Pyrophosphat;Pyrophosphate ion;Phosphonato phosphoric acid;Pyrophosphoric acid;Pyrophosphoric acid ionPW_C000170Ppi122354638429237353288222121731620492410592815294175144868545034895252104529410154091175424103543311854581205548111555913255841335606135565510858791076239166697819970731887134163727216073121987318213827515182832101186916112002222120411641231522512323249125122881257922612695290152193061537518347601742561315426973187723532977317128776353367841633578928331791531127995013479958130800473728041717085630194786384948141259481938298678223110634391113270395113275389115527136115532399119934122120017124120032406120330410120936407121261429121341121121486383122407422122985444123502119123831464124044398124977375125324297125395299125410479125597484125656485125876481126552491126869205126935388126950501127337206128124508140772891423MagnesiumHMDB0000547Magnesium salts are essential in nutrition, being required for the activity of many enzymes, especially those concerned with oxidative phosphorylation. Physiologically, it exists as an ion in the body. It is a component of both intra- and extracellular fluids and is excreted in the urine and feces. Deficiency causes irritability of the nervous system with tetany, vasodilatation, convulsions, tremors, depression, and psychotic behavior. Magnesium ion in large amounts is an ionic laxative, and magnesium sulfate (Epsom salts) is sometimes used for this purpose. So-called "milk of magnesia" is a water suspension of one of the few insoluble magnesium compounds, magnesium hydroxide; the undissolved particles give rise to its appearance and name. Milk of magnesia is a mild base, and is commonly used as an antacid.22537-22-0C003058881842013-HYDROXY-MAGNESIUM-PROTOPORP865DB01378[Mg++]MgInChI=1S/Mg/q+2JLVVSXFLKOJNIY-UHFFFAOYSA-Nmagnesium(2+) ion24.30523.9850418980magnesium(2+) ion22FDB003518Magnesium;Magnesium ions;Magnesium ion;Magnesium, doubly charged positive ion;Magnesium, ion (mg(2+));Mg(2+);Mg2+PW_C000423Mg2+86822742681647627272681158191888322936399833992211167461483491529431764142124102411592942233126293373745403147749148695449745652531045329111535611253761035906147593415160381556094161625016664841786594164688116069791997170205719420672272137233211725021473102167313198747322211763132118432101231222512324249125132881258122612729290152752851533730877137133772363297793733678393334784173357848911578522331785363567857413080020368800451848004837280623118806541358086515809652538184151938323839490027108596223110559390115687398119974406120070122120247382120702407120981408121181124121265429121319419121924125122086405122408422122759120122921399123307119123546374123835464123889455124477136124637376124978375125447297125598484125669479125777481125921482125947299125973495126000490126243478126553491126753300127125389127164501127380502127407388127451507127804209128125508128347395140773891457PotassiumHMDB0000586Potassium is an essential electrolyte. Potassium balance is crucial for regulating the excitability of nerves and muscles and so critical for regulating contractility of cardiac muscle. Although the most important changes seen in the presence of deranged potassium are cardiac, smooth muscle is also affected with increasing muscle weakness, a feature of both hyperkalaemia and hypokalaemia. Physiologically, it exists as an ion in the body. Potassium (K+) is a positively charged electrolyte, cation, which is present throughout the body in both intracellular and extracellular fluids. The majority of body potassium, >90%, are intracellular. It moves freely from intracellular fluid (ICF) to extracellular fluid (ECF) and vice versa when adenosine triphosphate increases the permeability of the cell membrane. It is mainly replaced inside or outside the cells by another cation, sodium (Na+). The movement of potassium into or out of the cells is linked to certain body hormones and also to certain physiological states. Standard laboratory tests measure ECF potassium. Potassium enters the body rapidly during food ingestion. Insulin is produced when a meal is eaten; this causes the temporary movement of potassium from ECF to ICF. Over the ensuing hours, the kidneys excrete the ingested potassium and homeostasis is returned. In the critically ill patient, suffering from hyperkalaemia, this mechanism can be manipulated beneficially by administering high concentration (50%) intravenous glucose. Insulin can be added to the glucose, but glucose alone will stimulate insulin production and cause movement of potassium from ECF to ICF. The stimulation of alpha receptors causes increased movement of potassium from ICF to ECF. A noradrenaline infusion can elevate serum potassium levels. An adrenaline infusion, or elevated adrenaline levels, can lower serum potassium levels. Metabolic acidosis causes a rise in extracellular potassium levels. In this situation, excess of hydrogen ions (H+) are exchanged for intracellular potassium ions, probably as a result of the cellular response to a falling blood pH. Metabolic alkalosis causes the opposite effect, with potassium moving into the cells. (PMID: 17883675).24203-36-9C0023881329103K%2b791DB01345[K+]KInChI=1S/K/q+1NPYPAHLBTDXSSS-UHFFFAOYSA-Npotassium(1+) ion39.098338.9637068610potassium(1+) ion11FDB003521K+;Kalium;Potassium;Potassium (k+);Potassium (ion);Potassium cation;Potassium ion;Potassium ion (k+);Potassium ion (k1+);Potassium ion(+);Potassium ion(1+);Potassium monocation;Potassium(+);Potassium(1+);Potassium(1+) ion;Potassium(i) cation;K(+)PW_C000457K+5738931191926220951530336631617231627136135136146159211475952151690216011810198152223067702322577115132776101117824132678246353120484122121198124123105135123768118124944452124949472125860297125965299127322205127421388140680834140681790140687781185SarcosineHMDB0000271Sarcosine is the N-methyl derivative of glycine. Sarcosine is metabolized to glycine by the enzyme sarcosine dehydrogenase, while glycine-N-methyl transferase generates sarcosine from glycine. Sarcosine is a natural amino acid found in muscles and other body tissues. In the laboratory it may be synthesized from chloroacetic acid and methylamine. Sarcosine is naturally found in the metabolism of choline to glycine. Sarcosine is sweet to the taste and dissolves in water. It is used in manufacturing biodegradable surfactants and toothpastes as well as in other applications. Sarcosine is ubiquitous in biological materials and is present in such foods as egg yolks, turkey, ham, vegetables, legumes, etc. Sarcosine is formed from dietary intake of choline and from the metabolism of methionine, and is rapidly degraded to glycine. Sarcosine has no known toxicity, as evidenced by the lack of phenotypic manifestations of sarcosinemia, an inborn error of sarcosine metabolism. Sarcosinemia can result from severe folate deficiency because of the folate requirement for the conversion of sarcosine to glycine (Wikipedia). Sarcosine has recently been identified as a biomarker for invasive prostate cancer. It was found to be greatly increased during prostate cancer progression to metastasis and could be detected in urine. Sarcosine levels were also increased in invasive prostate cancer cell lines relative to benign prostate epithelial cells.(PMID: 19212411).107-97-1C00213108815611SARCOSINE1057CNCC(O)=OC3H7NO2InChI=1S/C3H7NO2/c1-4-2-3(5)6/h4H,2H2,1H3,(H,5,6)FSYKKLYZXJSNPZ-UHFFFAOYSA-N2-(methylamino)acetic acid89.093289.0476784730.542sarcosine00FDB021925(methylamino)acetate;(methylamino)acetic acid;(methylamino)ethanoate;(methylamino)ethanoic acid;(methylamino)-acetate;(methylamino)-acetic acid;Methylglycine;N-methyl-glycine;N-methylaminoacetate;N-methylaminoacetic acid;N-methylglycine;Sarcosin;Sarcosinate;Sarcosine;Sarcosinic acid;Megly;Methylaminoacetic acid;Sar;2-(methylamino)acetate;MethylaminoacetatePW_C000185Sar188327255637808111278306351122127407122285435124679119124839470126284481126450499127847206128020517749S-AdenosylhomocysteineHMDB0000939S-Adenosyl-L-homocysteine (SAH) is formed by the demethylation of S-adenosyl-L-methionine. S-Adenosylhomocysteine (AdoHcy or SAH) is also the immediate precursor of all of the homocysteine produced in the body. The reaction is catalyzed by S-adenosylhomocysteine hydrolase and is reversible with the equilibrium favoring formation of SAH. In vivo, the reaction is driven in the direction of homocysteine formation by the action of the enzyme adenosine deaminase which converts the second product of the S-adenosylhomocysteine hydrolase reaction, adenosine, to inosine. Except for methyl transfer from betaine and from methylcobalamin in the methionine synthase reaction, SAH is the product of all methylation reactions that involve S-adenosylmethionine (SAM) as the methyl donor. Methylation is significant in epigenetic regulation of protein expression via DNA and histone methylation. The inhibition of these SAM-mediated processes by SAH is a proven mechanism for metabolic alteration. Because the conversion of SAH to homocysteine is reversible, with the equilibrium favoring the formation of SAH, increases in plasma homocysteine are accompanied by an elevation of SAH in most cases. Disturbances in the transmethylation pathway indicated by abnormal SAH, SAM, or their ratio have been reported in many neurodegenerative diseases, such as dementia, depression, and Parkinson's disease (PMID: 18065573, 17892439). Therefore, when present in sufficiently high levels, S-adenosylhomocysteine can act as an immunotoxin and a metabotoxin. An immunotoxin disrupts, limits the function, or destroys immune cells. A metabotoxin is an endogenous metabolite that causes adverse health effects at chronically high levels. Chronically high levels of S-adenosylhomocysteine are associated with S-adenosylhomocysteine (SAH) hydrolase deficiency and adenosine deaminase deficiency. S-Adenosylhomocysteine forms when there are elevated levels of homocysteine and adenosine. S-Adenosyl-L-homocysteine is a potent inhibitor of S-adenosyl-L-methionine-dependent methylation reactions. It is toxic to immature lymphocytes and can lead to immunosuppression (PMID: 221926).979-92-0C000212524622216680ADENOSYL-HOMO-CYS388301N[C@@H](CCSC[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=NC2=C1N=CN=C2N)C(O)=OC14H20N6O5SInChI=1S/C14H20N6O5S/c15-6(14(23)24)1-2-26-3-7-9(21)10(22)13(25-7)20-5-19-8-11(16)17-4-18-12(8)20/h4-7,9-10,13,21-22H,1-3,15H2,(H,23,24)(H2,16,17,18)/t6-,7+,9+,10+,13+/m0/s1ZJUKTBDSGOFHSH-WFMPWKQPSA-N(2S)-2-amino-4-({[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl}sulfanyl)butanoic acid384.411384.12158847-1.975S-adenosyl-L-homocysteine00DBMET00514FDB022327(s)-5'-(s)-(3-amino-3-carboxypropyl)-5'-thioadenosine;2-s-adenosyl-l-homocysteine;5'-deoxy-s-adenosyl-l-homocysteine;5'-s-(3-amino-3-carboxypropyl)-5'-thio-l-adenosine;Adenosyl-l-homocysteine;Adenosyl-homo-cys;Adenosylhomo-cys;Adenosylhomocysteine;Adohcy;Formycinylhomocysteine;L-5'-s-(3-amino-3-carboxypropyl)-5'-thior-adenosine;L-s-adenosyl-homocysteine;L-s-adenosylhomocysteine;S-(5'-adenosyl)-l-homocysteine;S-(5'-deoxyadenosin-5'-yl)-l-homocysteine;S-(5'-deoxyadenosine-5')-l-homocysteine;S-adenosyl-l-homocysteine;S-adenosyl-homocysteine;Sah;(2s)-2-amino-4-({[(2s,3s,4r,5r)-5-(6-amino-9h-purin-9-yl)-3,4-dihydroxytetrahydrofuran-2-yl]methyl}sulfanyl)butanoic acid;S-[1-(adenin-9-yl)-1,5-dideoxy-beta-d-ribofuranos-5-yl]-l-homocysteine;S-adenosylhomocysteinePW_C000749SAH520857518635307052012213188227206724683105025505607136713716375422107546213763416082681519237195118751981235922515294249153643097748911177611130777333387777334178098132783053517833734679156112799623618086322948313829483438611328738911328939711554439911554740112039412212048612512053941312094040712105312412228443512303713512317344912350611912361711812483847012588048112630329912644949912734120612759638812801951778GlycineHMDB0000123Glycine is a simple, nonessential amino acid, although experimental animals show reduced growth on low-glycine diets. The average adult ingests 3 to 5 grams of glycine daily. Glycine is involved in the body's production of DNA, phospholipids and collagen, and in release of energy. Glycine levels are effectively measured in plasma in both normal patients and those with inborn errors of glycine metabolism. (http://www.dcnutrition.com/AminoAcids/) Nonketotic hyperglycinaemia (OMIM 606899) is an autosomal recessive condition caused by deficient enzyme activity of the glycine cleavage enzyme system (EC 2.1.1.10). The glycine cleavage enzyme system comprises four proteins: P-, T-, H- and L-proteins (EC 1.4.4.2, EC 2.1.2.10 and EC 1.8.1.4 for P-, T- and L-proteins). Mutations have been described in the GLDC (OMIM 238300), AMT (OMIM 238310), and GCSH (OMIM 238330) genes encoding the P-, T-, and H-proteins respectively. The glycine cleavage system catalyses the oxidative conversion of glycine into carbon dioxide and ammonia, with the remaining one-carbon unit transferred to folate as methylenetetrahydrofolate. It is the main catabolic pathway for glycine and it also contributes to one-carbon metabolism. Patients with a deficiency of this enzyme system have increased glycine in plasma, urine and cerebrospinal fluid (CSF) with an increased CSF: plasma glycine ratio. (PMID 16151895).56-40-6C00037525712715428GLY730DB00145NCC(O)=OC2H5NO2InChI=1S/C2H5NO2/c3-1-2(4)5/h1,3H2,(H,4,5)DHMQDGOQFOQNFH-UHFFFAOYSA-N2-aminoacetic acid75.066675.0320284090.872glycine00FDB0004842-aminoacetate;2-aminoacetic acid;Aciport;Amino-acetate;Amino-acetic acid;Aminoacetate;Aminoacetic acid;Aminoethanoate;Aminoethanoic acid;Glicoamin;Glycocoll;Glycolixir;Glycosthene;Gyn-hydralin;Padil;Aminoessigsaeure;G;Gly;Glycin;Glykokoll;Glyzin;H2n-ch2-cooh;Hgly;LeimzuckerPW_C000078Gly314179818122188127282929542010354541205580133564010756411085863105600714770141607439374411667442151179419811872161124291511523322242419318424203157764433677742111780221327830435180708135120028406120097122120117124121687429122283435122850118124236464124837470125406479125466297125484299126448499126946501127003205127021388128018517120L-SerineHMDB0000187Serine is a nonessential amino acid derived from glycine. Like all the amino acid building blocks of protein and peptides, serine can become essential under certain conditions, and is thus important in maintaining health and preventing disease. Low-average concentration of serine compared to other amino acids is found in muscle. Serine is highly concentrated in all cell membranes. (http://www.dcnutrition.com/AminoAcids/) L-Serine may be derived from four possible sources: dietary intake; biosynthesis from the glycolytic intermediate 3-phosphoglycerate; from glycine ; and by protein and phospholipid degradation. Little data is available on the relative contributions of each of these four sources of l-serine to serine homoeostasis. It is very likely that the predominant source of l-serine will be very different in different tissues and during different stages of human development. In the biosynthetic pathway, the glycolytic intermediate 3-phosphoglycerate is converted into phosphohydroxypyruvate, in a reaction catalyzed by 3-phosphoglycerate dehydrogenase (3- PGDH; EC 1.1.1.95). Phosphohydroxypyruvate is metabolized to phosphoserine by phosphohydroxypyruvate aminotransferase (EC 2.6.1.52) and, finally, phosphoserine is converted into l-serine by phosphoserine phosphatase (PSP; EC 3.1.3.3). In liver tissue, the serine biosynthetic pathway is regulated in response to dietary and hormonal changes. Of the three synthetic enzymes, the properties of 3-PGDH and PSP are the best documented. Hormonal factors such as glucagon and corticosteroids also influence 3-PGDH and PSP activities in interactions dependent upon the diet. L-serine plays a central role in cellular proliferation. L-Serine is the predominant source of one-carbon groups for the de novo synthesis of purine nucleotides and deoxythymidine monophosphate. It has long been recognized that, in cell cultures, L-serine is a conditional essential amino acid, because it cannot be synthesized in sufficient quantities to meet the cellular demands for its utilization. In recent years, L-serine and the products of its metabolism have been recognized not only to be essential for cell proliferation, but also to be necessary for specific functions in the central nervous system. The findings of altered levels of serine and glycine in patients with psychiatric disorders and the severe neurological abnormalities in patients with defects of L-serine synthesis underscore the importance of L-serine in brain development and function. (PMID 12534373).56-45-1C00065595117115SER5736DB00133N[C@@H](CO)C(O)=OC3H7NO3InChI=1S/C3H7NO3/c4-2(1-5)3(6)7/h2,5H,1,4H2,(H,6,7)/t2-/m0/s1MTCFGRXMJLQNBG-REOHCLBHSA-N(2S)-2-amino-3-hydroxypropanoic acid105.0926105.0425930950.663L-serine00FDB012739(-)-serine;(s)-2-amino-3-hydroxypropanoate;(s)-2-amino-3-hydroxypropanoic acid;(s)-2-amino-3-hydroxy-propanoate;(s)-2-amino-3-hydroxy-propanoic acid;(s)-serine;(s)-a-amino-b-hydroxypropionate;(s)-a-amino-b-hydroxypropionic acid;(s)-alpha-amino-beta-hydroxypropionate;(s)-alpha-amino-beta-hydroxypropionic acid;(s)-b-amino-3-hydroxypropionate;(s)-b-amino-3-hydroxypropionic acid;(s)-beta-amino-3-hydroxypropionate;(s)-beta-amino-3-hydroxypropionic acid;2-amino-3-hydroxypropanoate;2-amino-3-hydroxypropanoic acid;3-hydroxy-l-alanine;L-(-)-serine;L-3-hydroxy-2-aminopropionate;L-3-hydroxy-2-aminopropionic acid;L-3-hydroxy-alanine;L-ser;Serine;B-hydroxy-l-alanine;Beta-hydroxy-l-alanine;Beta-hydroxyalanine;(2s)-2-amino-3-hydroxypropanoic acid;(s)-(-)-serine;L-2-amino-3-hydroxypropionic acid;L-serin;S;Ser;(2s)-2-amino-3-hydroxypropanoate;(s)-α-amino-β-hydroxypropionate;(s)-α-amino-β-hydroxypropionic acid;β-hydroxy-l-alanine;B-hydroxyalanine;β-hydroxyalanine;L-2-amino-3-hydroxypropionatePW_C000120Ser344818102261745642107564310858841056011147690716370862017087202709071709172720216074383744315744416675222248357225915424912173151126251815379494233531842336315773201117808813378112132799793319485838311575239811992412212205612412213640612271813512466711812468812012531429712620929912629347912686020512777138812785650111785,10-Methylene-THFHMDB00015335,10-Methylene-THF is an intermediate in glycine, serine and threonine metabolism and one carbon metabolism. 5,10-CH2-THF can also be used as a coenzyme in the biosynthesis of thymidine. More specifically it is the C1-donor in the reactions catalyzed by thymidylate synthase and thymidylate synthase (FAD). It also acts as a coenzyme in the synthesis of serine from glycine via the enzyme serine hydroxymethyl transferase. 5,10-Methylene-THF is a substrate for Methylenetetrahydrofolate reductase. This enzyme converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. This reaction is required for the multistep process that converts the amino acid homocysteine to methionine. The body uses methionine to make proteins and other important compounds. 5,10-CH2-THF is a substrate for many enzymes including Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase (mitochondrial), Aminomethyltransferase (mitochondrial), Serine hydroxymethyltransferase (mitochondrial), Methylenetetrahydrofolate reductase, C-1-tetrahydrofolate synthase (cytoplasmic), Serine hydroxymethyltransferase (cytosolic) and Thymidylate synthase.3432-99-3C0014343917515636METHYLENE-THF388320[H][C@@]12CN(CN1C1=C(NC2)N=C(N)NC1=O)C1=CC=C(C=C1)C(=O)NC(CCC(O)=O)C(O)=OC20H23N7O6InChI=1S/C20H23N7O6/c21-20-24-16-15(18(31)25-20)27-9-26(8-12(27)7-22-16)11-3-1-10(2-4-11)17(30)23-13(19(32)33)5-6-14(28)29/h1-4,12-13H,5-9H2,(H,23,30)(H,28,29)(H,32,33)(H4,21,22,24,25,31)/t12-,13?/m1/s1QYNUQALWYRSVHF-PZORYLMUSA-N2-({4-[(6aR)-1-hydroxy-3-imino-3H,4H,5H,6H,6aH,7H,8H,9H-imidazo[1,5-f]pteridin-8-yl]phenyl}formamido)pentanedioic acid457.4399457.170981503-2.7572-({4-[(6aR)-1-hydroxy-3-imino-4H,5H,6H,6aH,7H,9H-imidazo[1,5-f]pteridin-8-yl]phenyl}formamido)pentanedioic acid0-1FDB022675(6r)-5,10-methylenetetrahydrofolate;5,10-methenyltetrahydropteroylglutamate;5,10-methylene-6-hydrofolate;5,10-methylene-6-hydrofolic acid;5,10-methylene-thf;5,10-methylenetetrahydrofolate;5,10-methylenetetrahydrofolic acid;N5>,n10-methylenetetrahydrofolate;(6r)-5,10-methylenetetrahydrofolic acidPW_C0011785XM-THF44949568985318112533111153591125785108601014762723570651887171205719620675821634263931577339133781191321203554061206831221207044071221671241230041201232931351233091191247191181256764791257612971257794811263252991271715011278873881148Pyridoxal 5'-phosphateHMDB0001491This is the active form of vitamin B6 serving as a coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, aminolevulinic acid. During transamination of amino acids, pyridoxal phosphate is transiently converted into pyridoxamine phosphate (pyridoxamine). -- Pubchem; Pyridoxal-phosphate (PLP, pyridoxal-5'-phosphate) is a cofactor of many enzymatic reactions. It is the active form of vitamin B6 which comprises three natural organic compounds, pyridoxal, pyridoxamine and pyridoxine. -- Wikipedia.54-47-7C00018105118405PYRIDOXAL_PHOSPHATE1022DB00114CC1=NC=C(COP(O)(O)=O)C(C=O)=C1OC8H10NO6PInChI=1S/C8H10NO6P/c1-5-8(11)7(3-10)6(2-9-5)4-15-16(12,13)14/h2-3,11H,4H2,1H3,(H2,12,13,14)NGVDGCNFYWLIFO-UHFFFAOYSA-N[(4-formyl-5-hydroxy-6-methylpyridin-3-yl)methoxy]phosphonic acid247.1419247.024573569-1.643pyridoxal phosphate0-2FDB021820Apolon b6;Biosechs;Codecarboxylase;Coenzyme b6;Hairoxal;Hexermin-p;Hi-pyridoxin;Hiadelon;Himitan;Pal-p;Plp;Phosphopyridoxal;Phosphopyridoxal coenzyme;Pidopidon;Piodel;Pydoxal;Pyridoxal 5'-phosphate;Pyridoxal 5-phosphate;Pyridoxal p;Pyridoxal phosphate;Pyridoxal-p;Pyridoxyl phosphate;Pyromijin;Sechvitan;Vitahexin-p;Vitazechs;3-hydroxy-2-methyl-5-[(phosphonooxy)methyl]-4-pyridinecarboxaldehyde;3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde 5-phosphate;Phosphoric acid mono-(4-formyl-5-hydroxy-6-methyl-pyridin-3-ylmethyl) ester;Pyridoxal 5-monophosphoric acid ester;Pyridoxal 5'-(dihydrogen phosphate);Pyridoxal-5'-phosphate;Pyridoxal 5'-phosphoric acid;3-hydroxy-5-(hydroxymethyl)-2-methylisonicotinaldehyde 5-phosphoric acid;Phosphate mono-(4-formyl-5-hydroxy-6-methyl-pyridin-3-ylmethyl) ester;Pyridoxal 5-monophosphate ester;Pyridoxal 5'-(dihydrogen phosphoric acid);Pyridoxal 5-phosphoric acid;Pyridoxal phosphoric acid;Pyridoxal-5'-phosphoric acidPW_C001148Pyr-5'P1823244535181221401196962011104214505014582621201021504953251115416117542110354411185455120556713255811336533857018160716720572162127222213118581611217515112623311262818126842891268929077017253770372257704129377052224775261127776434177973346779793277829234578855332788623318069613598630711991212212002412412002940612008740712081741812114942312115542412206912312207638312283411912340245412372145812372745912462044712462739812530229712540229912540747912545848112580348912622429812623149512694238812694750112699620612725850612778651312779339040918TetrahydrofolateTetrahydrofolic acid, also known as tetrahydrofolate, belongs to the class of organic compounds known as tetrahydrofolic acids. These are heterocyclic compounds based on the 5,6,7,8-tetrahydropteroic acid skeleton conjugated with at least one L-glutamic acid unit. Tetrahydrofolic acid is considered to be a practically insoluble (in water) and relatively neutral molecule. Tetrahydrofolic acid has been found throughout most human tissues, and has also been detected in multiple biofluids, such as urine and blood. Tetrahydrofolic acid can be found anywhere throughout the human cell, such as in myelin sheath, lysosome, cytoplasm, and membrane (predicted from logP). In humans, tetrahydrofolic acid is involved in pterine biosynthesis pathway, the azathioprine action pathway, the sarcosine oncometabolite pathway, and the folate malabsorption, hereditary pathway. Tetrahydrofolic acid is also involved in several metabolic disorders, some of which include dihydropyrimidine dehydrogenase deficiency (DHPD), molybdenum cofactor deficiency, cystathionine Beta-synthase deficiency, and dimethylglycine dehydrogenase deficiency.C03541NC1=NC(=O)C2=C(NC[C@H](CNC3=CC=C(C=C3)C(=O)NC(CCC(O)=O)C(O)=O)N2)N1C19H23N7O6InChI=1S/C19H23N7O6/c20-19-25-15-14(17(30)26-19)23-11(8-22-15)7-21-10-3-1-9(2-4-10)16(29)24-12(18(31)32)5-6-13(27)28/h1-4,11-12,21,23H,5-8H2,(H,24,29)(H,27,28)(H,31,32)(H4,20,22,25,26,30)/t11-,12?/m0/s1MSTNYGQPCMXVAQ-PXYINDEMSA-N2-{[4-({[(6S)-4-hydroxy-2-imino-1,2,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)phenyl]formamido}pentanedioic acid445.4292445.170981503-3.2292-{[4-({[(6S)-4-hydroxy-2-imino-5,6,7,8-tetrahydro-1H-pteridin-6-yl]methyl}amino)phenyl]formamido}pentanedioic acid0-1PW_C040918tethf6012147120072221536MethylcobalaminHMDB0002274The name vitamin B12 is used in two different ways. In a broad sense it refers to a group of cobalt-containing compounds known as cobalamins - cyanocobalamin (an artifact formed as a result of the use of cyanide in the purification procedures), hydroxocobalamin and the two coenzyme forms of B12, methylcobalamin (MeB12) and 5-deoxyadenosylcobalamin (adenosylcobalamin - AdoB12). In a more specific way, the term B12 is used to refer to only one of these forms, cyanocobalamin, which is the principal B12 form used for foods and in nutritional supplements. B12 cannot be made by plants or by animals, as the only type of organisms that have the enzymes required for the synthesis of B12 are bacteria and archaea. The total synthesis of B12 was reported in 1973 by Robert Burns Woodward, and remains one of the classic feats of total synthesis. Cyanocobalamin is a vitamin commonly known as vitamin B12 (or B12 for short).13422-55-4C0645328115C1(CC[C@@]2([C@@H](CC(N)=O)[C@@]3([C@@]4([N+]5=C([C@H]([C@@]4(CC(N)=O)C)CCC(N)=O)C(C)=C4[N+]6=C(C=C7[N+]8=C([C@H](C7(C)C)CCC(N)=O)C(C)=C2N3[Co-3]568([N+]2=CN([C@H]3O[C@@H]([C@@H](OP(O[C@@H](CN1)C)([O-])=O)[C@H]3O)CO)C1=CC(C)=C(C=C21)C)C)[C@H]([C@@]4(CC(N)=O)C)CCC(N)=O)C)[H])C)=OC63H91CoN13O14PInChI=1S/C62H90N13O14P.CH3.Co/c1-29-20-39-40(21-30(29)2)75(28-70-39)57-52(84)53(41(27-76)87-57)89-90(85,86)88-31(3)26-69-49(83)18-19-59(8)37(22-46(66)80)56-62(11)61(10,25-48(68)82)36(14-17-45(65)79)51(74-62)33(5)55-60(9,24-47(67)81)34(12-15-43(63)77)38(71-55)23-42-58(6,7)35(13-16-44(64)78)50(72-42)32(4)54(59)73-56;;/h20-21,23,28,31,34-37,41,52-53,56-57,76,84H,12-19,22,24-27H2,1-11H3,(H15,63,64,65,66,67,68,69,71,72,73,74,77,78,79,80,81,82,83,85,86);1H3;/q;;+2/p-2/t31-,34-,35-,36-,37+,41-,52-,53-,56-,57+,59-,60+,61+,62+;;/m1../s1JEWJRMKHSMTXPP-WZHZPDAFSA-L(10S,12R,13S,17R,23R,24R,25R,30S,35S,36S,40S,41S,42R,46R)-30,35,40-tris(2-carbamoylethyl)-24,36,41-tris(carbamoylmethyl)-46-hydroxy-12-(hydroxymethyl)-1,5,6,17,23,28,31,31,36,38,41,42-dodecamethyl-15,20-dioxo-11,14,16-trioxa-2lambda5,9,19,26,43lambda5,44lambda5,45lambda5-heptaaza-15lambda5-phospha-1-cobaltadodecacyclo[27.14.1.1^{1,34}.1^{2,9}.1^{10,13}.0^{1,26}.0^{3,8}.0^{23,27}.0^{25,42}.0^{32,44}.0^{39,43}.0^{37,45}]heptatetraconta-2(47),3,5,7,27,29(44),32,34(45),37,39(43)-decaene-2,43,44,45-tetrakis(ylium)-1,1,1-triuid-15-olate1344.38231343.5878063919(10S,12R,13S,17R,23R,24R,25R,30S,35S,36S,40S,41S,42R,46R)-30,35,40-tris(2-carbamoylethyl)-24,36,41-tris(carbamoylmethyl)-46-hydroxy-12-(hydroxymethyl)-1,5,6,17,23,28,31,31,36,38,41,42-dodecamethyl-15,20-dioxo-11,14,16-trioxa-2lambda5,9,19,26,43lambda5,44lambda5,45lambda5-heptaaza-15lambda5-phospha-1-cobaltadodecacyclo[27.14.1.1^{1,34}.1^{2,9}.1^{10,13}.0^{1,26}.0^{3,8}.0^{23,27}.0^{25,42}.0^{32,44}.0^{39,43}.0^{37,45}]heptatetraconta-2(47),3,5,7,27,29(44),32,34(45),37,39(43)-decaene-2,43,44,45-tetrakis(ylium)-1,1,1-triuid-15-olate00FDB022939Algobaz;Co-methylcobalamin;Hitocobamin m;Mecbl;Mecobalamin;Methycobal;Methyl cobalamine;Methyl vitamin b12;Methyl-5,6-dimethylbenzimidazolylcobalamin;Methyl-b12;Methylcob(iii)alamin;Methylcobalamin;MethylcobazPW_C001536Mecbl41AcceptorCompoundPW_EC00004115339ChEBIAccepto40Reduced acceptorCompoundPW_EC00004015022ChEBIRA10470solute carrier family 44 A1Q8WWI5
Choline transporter. May be involved in membrane synthesis and myelin production.
SLC44A1114416630910471Choline transporter-like protein 2Q8IWA5
Isoform 1, but not isoform 3, exhibits some choline transporter activity.
SLC44A218975228196Choline dehydrogenase, mitochondrialQ8NE62HMDBP00201CHDH3p21.1AC01246711.1.99.156334663289761714210434914210655142108961287Alpha-aminoadipic semialdehyde dehydrogenaseP49419Multifunctional enzyme mediating important protective effects. Metabolizes betaine aldehyde to betaine, an important cellular osmolyte and methyl donor. Protects cells from oxidative stress by metabolizing a number of lipid peroxidation-derived aldehydes. Involved in lysine catabolism.
HMDBP00293ALDH7A15q31AC09951311.2.1.31; 1.2.1.3; 1.2.1.856181070314210726530Betaine--homocysteine S-methyltransferase 1Q93088Involved in the regulation of homocysteine metabolism. Converts betaine and homocysteine to dimethylglycine and methionine, respectively. This reaction is also required for the irreversible oxidation of choline.
HMDBP00559BHMT5q14.1AF11837312.1.1.556981878214211026397S-adenosylmethionine synthase isoform type-2P31153Catalyzes the formation of S-adenosylmethionine from methionine and ATP.
HMDBP00405MAT2A2p11.2BC00168612.5.1.636181927214300610762387Methionine adenosyltransferase 2 subunit betaQ9NZL9Non-catalytic regulatory subunit of S-adenosylmethionine synthetase 2 (MAT2A), an enzyme that catalyzes the formation of S-adenosylmethionine from methionine and ATP. Regulates the activity of S-adenosylmethionine synthetase 2 by changing its kinetic properties, rendering the enzyme more susceptible to S-adenosylmethionine inhibition.
HMDBP03965MAT2BAK31236513628192821430071076395Glycine N-methyltransferaseQ14749Catalyzes the methylation of glycine by using S-adenosylmethionine (AdoMet) to form N-methylglycine (sarcosine) with the concomitant production of S-adenosylhomocysteine (AdoHcy). Possible crucial role in the regulation of tissue concentration of AdoMet and of metabolism of methionine.
HMDBP00403GNMT6p12BC03262712.1.1.203472289778739Serine hydroxymethyltransferase, cytosolicP34896Interconversion of serine and glycine.
HMDBP00794SHMT117p11.2L2392812.1.2.1644818132142856104414300326198Dimethylglycine dehydrogenase, mitochondrialQ9UI17HMDBP00203DMGDH5q14.1AC02093711.5.8.4255731382483931440964738Sarcosine dehydrogenase, mitochondrialQ9UL12HMDBP00793SARDH9q33-q34AF14073611.5.8.325634737Serine hydroxymethyltransferase, mitochondrialP34897Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Required to prevent uracil accumulation in mtDNA. Interconversion of serine and glycine. Associates with mitochondrial DNA.
HMDBP00792SHMT212q12-q14AC13783412.1.2.126184144165310207UnknownUnknown12.3.1.85; 2.3.1.38; 2.3.1.39; 2.3.1.41; 1.1.1.100; 4.2.1.59; 1.3.1.39; 3.1.2.14; 3.5.99.5; 1.1.1.-640410642931643453916617917049182221167831168521212481212914121332291359735113617871400203081401567681405763091405898321408646014093348140954184141261831141275877141432931141584958141585959141586828142155261421941514226537214233223142671291426739961426839731428137871432728111432735214335575143398106514347411431434761314347896114351511481439341168143951118414395981014409423114412231123992Methionine synthaseQ99707
Catalyzes the transfer of a methyl group from methylcob(III)alamin (MeCbl) to homocysteine, yielding enzyme-bound cob(I)alamin and methionine in the cytosol (PubMed:27771510). MeCbl is an active form of cobalamin (vitamin B12) used as a cofactor for methionine biosynthesis. Cob(I)alamin form is regenerated to MeCbl by a transfer of a methyl group from 5-methyltetrahydrofolate (PubMed:27771510). The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR (methionine synthase reductase) and MTR which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine (PubMed:27771510).
MTR12.1.1.131428502143013107614416384195 solute carrier family 441PW_P00419511237104701123810471168Choline dehydrogenase, mitochondrial1PW_P0001681861961759641167Alpha-aminoadipic semialdehyde dehydrogenase1PW_P0001671852874169Betaine--homocysteine S-methyltransferase 11PW_P0001691875304761005486S-adenosylmethionine synthase1PW_P00008610039721012387115042361514573844Glycine N-methyltransferase1PW_P0008449693951193Serine hydroxymethyltransferase, cytosolic1PW_P00019321173948811481652Dimethylglycine dehydrogenase, mitochondrial1PW_P0006527201983039641654Sarcosine dehydrogenase, mitochondrial1PW_P0006547227383049641671Serine hydroxymethyltransferase, mitochondrial1PW_P0006717457373061148113578Unknown transport protein1PW_P013578234501020715550Methionine synthase cytosolic1PW_P015550257242399216181005161915361428512668falsePW_R000668Right2746651Compoundfalse8327411ElementCollectiontrue27479671Compoundfalse8328401ElementCollectiontrue1651681.1.99.1667falsePW_R000667Right27419671Compoundfalse27427211Compoundtrue274314201Compoundtrue2744301Compoundfalse274511441Compoundtrue164167669falsePW_R000669Right2748301Compoundfalse27495901Compoundfalse2750621Compoundfalse27515481Compoundfalse1661692.1.1.5671falsePW_R000671Right27564141Compoundtrue27575481Compoundfalse275814201Compoundtrue27599211Compoundfalse276011041Compoundtrue27611701Compoundtrue168862.5.1.61781falsePW_R001781Both66701851Compoundfalse66717491Compoundtrue66729211Compoundtrue6673781Compoundfalse15208442.1.1.201791falsePW_R001791Both67051201Compoundfalse670612211Compoundtrue6707781Compoundfalse670811781Compoundtrue670914201Compoundtrue15271932.1.2.16244falsePW_R006244Right25537621Compoundfalse25538409181Compoundtrue255391851Compoundfalse2554010791Compoundtrue61736526245falsePW_R006245Right255411851Compoundfalse25542409181Compoundtrue2554310791Compoundtrue25544781Compoundfalse61746546246falsePW_R006246Both255451201Compoundfalse25546409181Compoundtrue25547781Compoundfalse2554810791Compoundtrue61756712.1.2.1218409PW_R218409Both8420695901Compoundfalse84207010791Compoundfalse8420715481Compoundfalse84207212211Compoundfalse207829155502.1.1.13521PW_T000521665651Compound73Right45041952015-12-01T12:48:29-07:002015-12-01T12:48:29-07:0017522PW_T000522666301Compound37Right1588135782019-08-12T14:47:35-06:002019-08-12T14:47:35-06:0017523PW_T000523667621Compound73Right1590135782019-08-12T15:59:46-06:002019-08-12T15:59:46-06:00177768365781false22974410regular2001907768465381false82474410regular20019077687967381false153974910regular2001907768896439false124979610regular1002577689721359false176472610regular5030776901420349false176091610regular78787769130381false221474210regular200190776921144360false212972210regular50307769330881false283974210regular20019077694590881false314967210regular2001907769562881false2839114210regular20019077696548881false3134116710regular20019077697100589false288998710regular10025776991079881false343974210regular200190777001221881false3439113710regular20019077702414842false3076137210regular5030777031420849false3331135310regular787877704921881false3129165710regular200190777051104846false3104160010regular444377706170845false3308160010regular63437770742389false3182146419regular100257770845789false3097143410regular1002577709185881false4004165710regular20019077710749881false3744182710regular2001907771178881false3294187210regular20019077712120881false3295240710regular200190777131221881false3500227210regular200190777141178881false3501200710regular200190777151420849false3196206310regular787877716114889false3345218720regular100357771762381false2269114210regular2001907771840918381false2139134210regular20019077719185381false1694114410regular200190777201079381false1829134410regular2001907772196439false2034119210regular100257772240918381false1494135410regular200190777231079381false1089135110regular2001907772478381false884114110regular2001907772596439false1349119410regular1002577727120381false884186110regular2001907772840918381false694164110regular200190777291079381false694135110regular20019077730114839false934154819regular100353167438100589false348998919regular100253167439153689false348997419regular100251551411443false103990412regular150701552401443false137989912regular15070373611047030976false5047548subunitregular15070373621047122876false5048048subunitregular1507037364196172false12248068subunitregular150703736528738false19198028subunitregular140853736653088false28699878subunitregular140853736839786false306714348subunitregular1608037369238782false315714748subunitregular150703737039582false358917148subunitregular150703737173988false332521928subunitregular140853737219832false201412028subunitregular15070373737384232false132412048subunitregular150703737473732false90915688subunitregular150709643811020776false25398028subunitregular150709643841020730976false253612028subunitregular1507012259702399282false34649898subunitregular1507030460419521463093669937361367003736230462168214633670237364410677688111937Cofactor3046316721463367033736530464169214683670437366410777697111951Cofactor30466862146836706373683670737369410977707111963Cofactor411077708111964Cofactor3046784421468367083737030468193214683670937371411177716111974Cofactor30469652214633671037372411277721111981Cofactor30470654214633671137373411377725111986Cofactor30471671214633671237374411477730111991Cofactor8165661357821469601469643818165681357821463099601499643849640761555021468121958012259704845331674384334653Cofactor4845431674394334654Cofactor111928M429 839 C459 839 474 839 504 839 83false18111929M824 839 C794 839 684 839 654 839 83false18trueM 195.94685504416483 39.26155629629604 L 181 38 L 187.38088772118584 51.575134323078345false111935M1024 839 C1054 839 1194 841 1224 841 5false18111936M1539 844 C1509 844 1404 841 1374 841 5false18trueM 626.9468550441649 393.261556296296 L 612 392 L 618.3808877211858 405.5751343230783false111937M1054 731.5 L1054 781.5 L1104 731.5 z10true18111938M1114 904 C1116 831 1194 841 1224 841 5false18111939M1454 899 C1454 862 1404 841 1374 841 5false18trueM 626.9468550441649 393.261556296296 L 612 392 L 618.3808877211858 405.5751343230783false111940M1739 844 C1769 844 1889 842 1919 842 5false18111941M1789 756 C1791 842 1871 843 1919 842 5false18111942M1799 916 C1801 842 1889 842 1919 842 5false18111943M2214 837 C2184 837 2089 842 2059 842 5false18trueM 626.9468550441649 397.261556296296 L 612 396 L 618.3808877211858 409.5751343230783false111944M2154 752 C2151 828 2089 842 2059 842 5false18trueM 626.9468550441649 397.261556296296 L 612 396 L 618.3808877211858 409.5751343230783false111947M2939 932 C2939 962 2939 957 2939 987 5false18111948M3249 862 C3210 878 2983 969 2939 987 5false18111949M2939 1142 C2939 1112 2939 1102 2939 1072 5false18trueM 2327.9468550441647 397.261556296296 L 2313 396 L 2319.380887721186 409.5751343230783false111950M3234 1167 C3200 1151 2974 1085 2939 1072 5false18trueM 2327.9468550441647 397.261556296296 L 2313 396 L 2319.380887721186 409.5751343230783false111951M2824 957 L2824 1007 L2874 957 z10true18111957M3126 1387 C3222 1392 3232 1444 3232 1474 5false18111958M3234 1357 C3234 1387 3232 1444 3232 1474 5false18111959M3331 1392 C3238 1396 3232 1444 3232 1474 5false18111960M3229 1657 C3229 1627 3232 1574 3232 1544 5false18trueM 2666.9468550441647 966.261556296296 L 2652 965 L 2658.380887721186 978.5751343230784false111961M3148 1621.5 C3243 1619.5 3232 1574 3232 1544 5false18trueM 2666.9468550441647 966.261556296296 L 2652 965 L 2658.380887721186 978.5751343230784false111962M3308 1621.5 C3219 1618.5 3232 1574 3232 1544 5false18trueM 2666.9468550441647 966.261556296296 L 2652 965 L 2658.380887721186 978.5751343230784false111963M3012.5 1379.5 L3012.5 1429.5 L3062.5 1379.5 z10true18111964M3012.5 1359.5 L3012.5 1409.5 L3062.5 1359.5 z10true18111965M4004 1752 C3974 1752 3795 1749 3765 1749 5false18trueM 2666.9468550441647 1112.261556296296 L 2652 1111 L 2658.380887721186 1124.5751343230784false111966M3844 1827 C3843 1766 3789 1749 3739 1749 5false18trueM 2666.9468550441647 1112.261556296296 L 2652 1111 L 2658.380887721186 1124.5751343230784false111967M3329 1752 C3359 1752 3559 1749 3589 1749 5false18trueM 2666.9468550441647 1112.261556296296 L 2652 1111 L 2658.380887721186 1124.5751343230784false111968M3394 1872 C3394 1796 3490 1750 3589 1749 5false18trueM 2666.9468550441647 1112.261556296296 L 2652 1111 L 2658.380887721186 1124.5751343230784false111969M3395 2407 C3395 2377 3395 2307 3395 2277 5false18trueM 2528.9468550441647 1321.261556296296 L 2514 1320 L 2520.380887721186 1333.5751343230784false111970M3500 2367 C3427 2367 3395 2307 3395 2277 5false18trueM 2528.9468550441647 1321.261556296296 L 2514 1320 L 2520.380887721186 1333.5751343230784false111971M3394 2062 C3394 2092 3395 2162 3395 2192 5false18trueM 2528.9468550441647 1321.261556296296 L 2514 1320 L 2520.380887721186 1333.5751343230784false111972M3501 2102 C3409 2105 3395 2162 3395 2192 5false18trueM 2528.9468550441647 1321.261556296296 L 2514 1320 L 2520.380887721186 1333.5751343230784false111973M3274 2102 C3401 2104 3395 2162 3395 2192 5false18trueM 2528.9468550441647 1321.261556296296 L 2514 1320 L 2520.380887721186 1333.5751343230784false111974M3080 1602 L3080 1652 L3130 1602 z10true18111977M2269 1237 C2239 1237 2194 1237 2164 1237 5false18111978M2239 1342 C2238 1264 2224 1237 2164 1237 5false18111979M1894 1239 C1924 1239 1984 1237 2014 1237 5false18trueM 1525.9468550441647 837.261556296296 L 1511 836 L 1517.380887721186 849.5751343230784false111980M1929 1344 C1931 1249 1978 1237 2014 1237 5false18trueM 1525.9468550441647 837.261556296296 L 1511 836 L 1517.380887721186 849.5751343230784false111981M2114 1107 L2114 1157 L2164 1107 z10true18111982M1694 1239 C1664 1239 1504 1239 1474 1239 5false18111983M1594 1354 C1592 1267 1572 1238 1474 1239 5false18111984M1189 1351 C1192 1256 1294 1239 1324 1239 5false18trueM 655.9468550441649 753.261556296296 L 641 752 L 647.3808877211858 765.5751343230784false111985M1084 1236 C1114 1236 1294 1239 1324 1239 5false18trueM 655.9468550441649 753.261556296296 L 641 752 L 647.3808877211858 765.5751343230784false111986M1514 1109 L1514 1159 L1564 1109 z10true18111987M984 1861 C984 1831 984 1668 984 1638 5false18trueM 486.94685504416486 951.261556296296 L 472 950 L 478.38088772118584 963.5751343230784false111988M894 1736 C995 1736 984 1668 984 1638 5false18trueM 486.94685504416486 951.261556296296 L 472 950 L 478.38088772118584 963.5751343230784false111989M984 1331 C984 1361 984 1538 984 1568 5false18trueM 486.94685504416486 951.261556296296 L 472 950 L 478.38088772118584 963.5751343230784false111990M894 1446 C991 1448 984 1538 984 1568 5false18trueM 486.94685504416486 951.261556296296 L 472 950 L 478.38088772118584 963.5751343230784false111991M844 1378.5 L844 1428.5 L894 1378.5 z10true183720976M2414 837 C2444 837 2509 837 2539 837 83false183720977M2839 837 C2809 837 2719 837 2689 837 83false18trueM 2040.9468550441647 477.261556296296 L 2026 476 L 2032.380887721186 489.5751343230783false3720980M2839 1237 C2809 1237 2716 1237 2686 1237 83false183720981M2469 1237 C2499 1237 2506 1237 2536 1237 83false18trueM 2042.9468550441647 714.261556296296 L 2028 713 L 2034.380887721186 726.5751343230784false4334649M3249 862 C3288 878 3484 963 3539 989 5false18trueM 2466.9468550441647 442.261556296296 L 2452 441 L 2458.380887721186 454.5751343230783false4334650M3539 932 C3539 962 3539 959 3539 989 5false18trueM 2466.9468550441647 442.261556296296 L 2452 441 L 2458.380887721186 454.5751343230783false4334651M3234 1167 C3294 1145 3497 1073 3539 1059 5false18trueM 2466.9468550441647 442.261556296296 L 2452 441 L 2458.380887721186 454.5751343230783false4334652M3539 1137 C3539 1107 3539 1089 3539 1059 5false18trueM 2466.9468550441647 442.261556296296 L 2452 441 L 2458.380887721186 454.5751343230783false4334653M3334 999.5 L3334 1049.5 L3384 999.5 z10true184334654M3334 979.5 L3334 1029.5 L3384 979.5 z10true1822966214666838819077684111935Left8819177687111936Right17961551111938Left17971552111939Right227911653046222967214666738819277687111940Left8819377689111941Left8819477690111942Left8819577691111943Right8819677692111944Right227921643046322968214666988819777693111947Left8819877694111948Left8819977695111949Right8820077696111950Right227931663046422970214667188820577702111957Left8820677696111958Left8820777703111959Left8820877704111960Right8820977705111961Right8821077706111962Right2279516830466229712146178188821177709111965Left8821277710111966Left8821377704111967Right8821477711111968Right22796152030467229722146179188821577712111969Left8821677713111970Left8821777711111971Right8821877714111972Right8821977715111973Right22797152730468229732146624438822077717111977Left8822177718111978Left8822277719111979Right8822377720111980Right22798617330469229742146624538822477719111982Left8822577722111983Left8822677723111984Right8822777724111985Right22799617430470229752146624638822877727111987Left8822977728111988Left8823077724111989Right8823177729111990Right22800617530471928400214621840983773081776944334649Left3773082776994334650Left3773083776964334651Right3773084777004334652Right88136420782996407610125212146247577683111928Left247677684111929Right75930460450785375222146157897776913720976Left157898776933720977Right249958165661588785395232146157901776953720980Left157902777173720981Right24997816568159014688342331.01.00214902401469383915601.31.302514002741470152210481.31.30251400274147172010481.31.3025240027418728636082002.22.2031432726747989641684901.91.965232803604225M129 227 C129 177 179 127 229 127 C1471 127 3084 127 4326 127 C4376 127 4426 177 4426 227 C4426 954 4426 1899 4426 2626 C4426 2676 4376 2726 4326 2726 C3084 2726 1471 2726 229 2726 C179 2726 129 2676 129 2626 C129 1899 129 954 129 227 1true64297.02599.04226M529 640 C529 590 579 540 629 540 C1214 540 1973 540 2558 540 C2608 540 2658 590 2658 640 C2658 1090 2658 1676 2658 2126 C2658 2176 2608 2226 2558 2226 C1973 2226 1214 2226 629 2226 C579 2226 529 2176 529 2126 C529 1676 529 1090 529 640 84true62129.01686.04227M630 723 C630 673 680 623 730 623 C1256 623 1941 623 2467 623 C2517 623 2567 673 2567 723 C2567 1118 2567 1632 2567 2027 C2567 2077 2517 2127 2467 2127 C1941 2127 1256 2127 730 2127 C680 2127 630 2077 630 2027 C630 1632 630 1118 630 723 84true61937.01504.01807235Intracellular space1599213201.61.6200151808235Mitochondrion924223201.31.320015180915Outer Mitochondrial Membrane744463201.91.916015181015Inner Mitochondrial Membrane749548201.91.9160151811235Upregulated Expression35331615201.31.3200151812235Mutant SARDH12651098201.31.3200157041007328501514268422524#FFEBEB421831738