115406PathwayMetabolism and Physiological Effects of Para-cresolPara-cresol(P-cresol) is a phenolic compound that is formed through gut microbial metabolism from the amino acid tyrosine which is acquired from foods that are high in protein. After being transported into gut microbes, tyrosine undergoes reactions with the enzymes tyrosine transaminase, 4-hydroxyphenylpyruvate oxidase and 4-hydroxylphenylacetate decarboxylase to form para-cresol. Most of the p-cresol that is produced from the gut microbes then enters systemic circulation. P-cresol can then undergo sulfation or glucuronidation reactions in the liver to produce the uremic toxins p-cresyl sulfate and p-cresyl glucuronide respectively. However, P-cresol itself can also be a uremic toxin with widespread toxic effects on the body. P-cresol is shown to be associated with cardiovascular disease and it can also inhibit endothelial cell proliferation. MetabolicPW124564CenterPathwayVisualizationContext12484026503850#000099PathwayVisualization115269115406Metabolism and Physiological Effects of Para-cresolPara-cresol(P-cresol) is a phenolic compound that is formed through gut microbial metabolism from the amino acid tyrosine which is acquired from foods that are high in protein. After being transported into gut microbes, tyrosine undergoes reactions with the enzymes tyrosine transaminase, 4-hydroxyphenylpyruvate oxidase and 4-hydroxylphenylacetate decarboxylase to form para-cresol. Most of the p-cresol that is produced from the gut microbes then enters systemic circulation. P-cresol can then undergo sulfation or glucuronidation reactions in the liver to produce the uremic toxins p-cresyl sulfate and p-cresyl glucuronide respectively. However, P-cresol itself can also be a uremic toxin with widespread toxic effects on the body. P-cresol is shown to be associated with cardiovascular disease and it can also inhibit endothelial cell proliferation. Metabolic1113790Cardiovascular DiseaseActivatingSubPathway1135531232Compound113791Chronic Kidney diseaseActivatingSubPathway1135541232Compound113972Inhibition of endothelial cell proliferation SubPathway1137971232Compound336121Meyer, T. W., & Hostetter, T. H. (2012). Uremic solutes from colon microbes. Kidney international, 81(10), 949-954.115406Pathway336122Passmore, I. J., Letertre, M. P., Preston, M. D., Bianconi, I., Harrison, M. A., Nasher, F., ... & Dawson, L. F. (2018). Para-cresol production by Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria. PLoS pathogens, 14(9), e1007191.115406Pathway336123Selmer, T., & Andrei, P. I. (2001). p‐Hydroxyphenylacetate decarboxylase from Clostridium difficile: A novel glycyl radical enzyme catalysing the formation of p‐cresol. European Journal of Biochemistry, 268(5), 1363-1372.115406Pathway336124Dawson, L. F., Donahue, E. H., Cartman, S. T., Barton, R. H., Bundy, J., McNerney, R., ... & Wren, B. W. (2011). The analysis of para-cresol production and tolerance in Clostridium difficile 027 and 012 strains. BMC microbiology, 11(1), 1-10.115406Pathway336125Steglich, M., Hofmann, J. D., Helmecke, J., Sikorski, J., Spröer, C., Riedel, T., ... & Nübel, U. (2018). Convergent loss of ABC transporter genes from Clostridioides difficile genomes is associated with impaired tyrosine uptake and p-cresol production. Frontiers in microbiology, 9, 901.115406Pathway33612620216Blakley ER: The catabolism of L-tyrosine by an Arthrobacter sp. Can J Microbiol. 1977 Sep;23(9):1128-39. doi: 10.1139/m77-169.115406Pathway33612728146081Gryp T, Vanholder R, Vaneechoutte M, Glorieux G: p-Cresyl Sulfate. Toxins (Basel). 2017 Jan 29;9(2). pii: toxins9020052. doi: 10.3390/toxins9020052.115406Pathway336140Meijers, B. K. I., Bammens, B., De Moor, B., Verbeke, K., Vanrenterghem, Y., & Evenepoel, P. (2008). Free p-cresol is associated with cardiovascular disease in hemodialysis patients. Kidney international, 73(10), 1174-1180.115406Pathway1CellCL:00000003NeuronCL:00005402Platelet CL:00002336MyocyteCL:00001875HepatocyteCL:000018212AstrocyteCL:00001277Epithelial CellCL:000006628MacrophageCL:00002354CardiomyocyteCL:00007461Homo sapiens9606EukaryoteHuman12Mus musculus10090EukaryoteMouse5Bos taurus9913EukaryoteCattle17Rattus norvegicus10116EukaryoteRat6Caenorhabditis elegans6239EukaryoteRoundworm3Escherichia coli562Prokaryote4Arabidopsis thaliana3702EukaryoteThale cress23Pseudomonas aeruginosa287Prokaryote24Solanum lycopersicum4081EukaryoteTomato18Saccharomyces cerevisiae4932EukaryoteYeast49Bathymodiolus platifrons220390EukaryoteDeep sea mussel10Drosophila melanogaster7227EukaryoteFruit fly2Bacteria2ProkaryoteBacteria21Xenopus laevis8355EukaryoteAfrican clawed frog60Nitzschia sp.0001EukaryoteNitzschia4196Homo1924EukaryoteHuman157Acinetobacter baumannii 107673Prokaryote280Bacteroides fragilis55247009Prokaryote209Clostridium difficile1496Eukaryote129Candida albicans5476Eukaryote186Human immunodeficiency virus type 111676EukaryoteHIV-11CytosolGO:00058295CytoplasmGO:000573715NucleusGO:000563431Periplasmic SpaceGO:000562011Extracellular SpaceGO:000561535ChloroplastGO:00095072MitochondrionGO:000573954Endocytic VesicleGO:003013955Exocytic VesicleGO:00703826LysosomeGO:00057644PeroxisomeGO:000577713Endoplasmic ReticulumGO:000578310Cell MembraneGO:000588616Lysosomal LumenGO:00432027Endoplasmic Reticulum MembraneGO:00057893Mitochondrial MatrixGO:000575918Melanosome MembraneGO:003316214Mitochondrial Outer MembraneGO:000574124Mitochondrial Intermembrane SpaceGO:000575836MembraneGO:001602012Mitochondrial Inner MembraneGO:000574325Golgi ApparatusGO:000579432Inner MembraneGO:007025837Basolateral cell membraneGO:001632349Nuclear EnvelopeGO:000563539Mitochondrial membraneGO:003196656Basal Cell MembraneGO:000992538Apical cell membraneGO:001632420Endoplasmic Reticulum LumenGO:000578858Cell WallGO:000561830Lysosomal MembraneGO:00057653Sympathetic Nervous SystemBTO:00018324Adrenal MedullaBTO:00000497182Endothelium BTO:00003931LiverBTO:000075972928StomachBTO:0001307155269MuscleBTO:00008871411824BrainBTO:000014289168Blood 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acidHMDB0000020p-Hydroxyphenylacetic acid is an oxidative deaminated metabolite of p-tyramine. Also a metabolite of tyrosine via enteric bacteria. The bacterial origin of this compound was confirmed by the finding that this compound in urine decreased significantly after the use of the antibiotic neomycin.156-38-7C00642127181014-HYDROXYPHENYLACETATE124OC(=O)CC1=CC=C(O)C=C1C8H8O3InChI=1S/C8H8O3/c9-7-3-1-6(2-4-7)5-8(10)11/h1-4,9H,5H2,(H,10,11)XQXPVVBIMDBYFF-UHFFFAOYSA-N2-(4-hydroxyphenyl)acetic acid152.1473152.047344122-1.3324-hydroxyphenylacetic acid0-1FDB010534(4-hydroxy-phenyl)-essigsaeure;(4-hydroxy-phenyl)-acetate;(4-hydroxy-phenyl)-acetic acid;(4-hydroxyphenyl)acetate;(4-hydroxyphenyl)acetic acid;(p-hydroxyphenyl)acetate;(p-hydroxyphenyl)acetic acid;(p-hydroxyphenyl)-acetate;(p-hydroxyphenyl)-acetic acid;4-hydroxy-benzeneacetate;4-hydroxy-benzeneacetic acid;4-hydroxybenzeneacetate;4-hydroxybenzeneacetic acid;4-hydroxyphenylacetate;4-hydroxyphenylacetic acid;4-hydroxyphenyl-acetic acid;Parahydroxy phenylacetate;Parahydroxy phenylacetic acid;Parahydroxyphenylacetate;P-hydroxyphenylacetate;P-hydroxyphenylacetic acid;4-carboxymethylphenolPW_C000013p-Hpaa20142791101321216041241241621181275713881232p-CresolHMDB0001858p-Cresol (4-methylphenol), a 108.1 Da volatile low-molecular-weight compound, is a phenol. It is a partially lipophilic moiety which strongly binds to plasma protein (close to 100%) under normal conditions. p-Cresol is metabolized through conjugation, mainly sulphation and glucuronization, but removal of the unconjugated p-cresol is, at least in part, via the urine. Therefore it is not surprising that this compound, together with several other phenoles, is retained when the kidneys fail. P-Cresol is an end-product of protein breakdown, and an increase of the nutritional protein load in healthy individuals results in enhanced generation and urinary excretion. The serum p-cresol concentration in uremic patients can be decreased by changing to a low-protein diet. p-Cresol is one of the metabolites of the amino acid tyrosine, and to a certain extent also of phenylalanine, which are converted to 4-hydroxyphenylacetic acid by intestinal bacteria, before being decarboxylated to p-cresol (putrefaction). The main contributing bacteria are aerobes (mainly enterobacteria), but to a certain extent also anaerobes play a role (mainly Clostridium perfringens). In uremia, modifications in the intestinal flora result in the specific overgrowth of bacteria that are specific p-cresol producers. The administration of antibiotics reduces urinary excretion of p-cresol, as a result of the liquidation of the producing bacteria. Environmental factors might also contribute. The liver cytochrome P450 metabolizes toluene to benzyl alcohol, but also to o-cresol and p-cresol. Toluene is not only used industrially, but it is also the most widely abusively inhaled solvent. Furthermore, p-cresol is a metabolite of menthofuran, one of the metabolites of R-(+)-pulegone, which is found in extracts from the plants Mentha pulegium and Hedeoma pulegioides, commonly known as pennyroyal oil and pennyroyal tea. These extracts are popular as unconventional herbal therapeutic agents and are applied as abortiva, diaphoretics, emmenagogues, and psychedelic drugs. Pennyroyal oil is extensively used for its pleasant mint-like smell in the flavoring industry. The toxicity of pennyroyal oil and menthofuran is well known. Another compound used in traditional medicine, especially in Japan, which is a precursor of p-cresol is wood tar creosote. p-Cresol has been reported to affect several biochemical, biological and physiological functions: (i) it diminishes the oxygen uptake of rat cerebral cortex slices; (ii) it increases the free active drug concentration of warfarin and diazepam; (iii) it has been related to growth retardation in the weanling pig; (iv) it alters cell membrane permeability, at least in bacteria; (v) it induces LDH leakage from rat liver slices; (vi) it induces susceptibility to auditive epileptic crises; and (vii) it blocks cell K+ channels. (PMID: 10570076). p-Cresol is a uremic toxin that is at least partially removed by peritoneal dialysis in haemodialysis patients, and has been involved in the progression of renal failure. (MID: 11169029). At concentrations encountered during uremia, p-cresol inhibits phagocyte function and decreases leukocyte adhesion to cytokine-stimulated endothelial cells. (PMID: 14681860).106-44-5C01468287917847CPD-10813839082DB01688CC1=CC=C(O)C=C1C7H8OInChI=1S/C7H8O/c1-6-2-4-7(8)5-3-6/h2-5,8H,1H3IWDCLRJOBJJRNH-UHFFFAOYSA-N4-methylphenol108.1378108.057514878-0.671P-cresol00FDB0087891-hydroxy-4-methylbenzene;1-methyl-4-hydroxybenzene;4-(pentafluorosulfanyl)phenol;4-cresol;4-hydroxytoluene;4-methyl phenol;4-methylphenol;Paracresol;Paramethyl phenol;P-cresol;P-cresylate;P-cresylic acid;P-hydroxytoluene;P-kresol;P-methyl phenol;P-methylhydroxybenzene;P-oxytoluene;P-toluol;P-tolyl alcohol;4-methyl-phenolPW_C001232PCresol103L-TyrosineHMDB0000158Tyrosine is an essential amino acid that readily passes the blood-brain barrier. Once in the brain, it is a precursor for the neurotransmitters dopamine, norepinephrine and epinephrine, better known as adrenalin. These neurotransmitters are an important part of the body's sympathetic nervous system, and their concentrations in the body and brain are directly dependent upon dietary tyrosine. Tyrosine is not found in large concentrations throughout the body, probably because it is rapidly metabolized. Folic acid, copper and vitamin C are cofactor nutrients of these reactions. Tyrosine is also the precursor for hormones, thyroid, catecholestrogens and the major human pigment, melanin. Tyrosine is an important amino acid in many proteins, peptides and even enkephalins, the body's natural pain reliever. Valine and other branched amino acids, and possibly tryptophan and phenylalanine may reduce tyrosine absorption. A number of genetic errors of tyrosine metabolism occur. Most common is the increased amount of tyrosine in the blood of premature infants, which is marked by decreased motor activity, lethargy and poor feeding. Infection and intellectual deficits may occur. Vitamin C supplements reverse the disease. Some adults also develop elevated tyrosine in their blood. This indicates a need for more vitamin C. More tyrosine is needed under stress, and tyrosine supplements prevent the stress-induced depletion of norepinephrine and can cure biochemical depression. However, tyrosine may not be good for psychosis. Many antipsychotic medications apparently function by inhibiting tyrosine metabolism. L-dopa, which is directly used in Parkinson's, is made from tyrosine. Tyrosine, the nutrient, can be used as an adjunct in the treatment of Parkinson's. Peripheral metabolism of tyrosine necessitates large doses of tyrosine, however, compared to L-dopa. (http://www.dcnutrition.com).60-18-4C00082605717895TYR5833DB00135N[C@@H](CC1=CC=C(O)C=C1)C(O)=OC9H11NO3InChI=1S/C9H11NO3/c10-8(9(12)13)5-6-1-3-7(11)4-2-6/h1-4,8,11H,5,10H2,(H,12,13)/t8-/m0/s1OUYCCCASQSFEME-QMMMGPOBSA-N(2S)-2-amino-3-(4-hydroxyphenyl)propanoic acid181.1885181.073893223-1.373L-tyrosine00FDB000446(-)-a-amino-p-hydroxyhydrocinnamate;(-)-a-amino-p-hydroxyhydrocinnamic acid;(-)-alpha-amino-p-hydroxyhydrocinnamate;(-)-alpha-amino-p-hydroxyhydrocinnamic acid;(s)-(-)-tyrosine;(s)-2-amino-3-(p-hydroxyphenyl)propionate;(s)-2-amino-3-(p-hydroxyphenyl)propionic acid;(s)-3-(p-hydroxyphenyl)alanine;(s)-tyrosine;(s)-a-amino-4-hydroxybenzenepropanoate;(s)-a-amino-4-hydroxybenzenepropanoic acid;(s)-a-amino-4-hydroxy-benzenepropanoate;(s)-a-amino-4-hydroxy-benzenepropanoic acid;(s)-alpha-amino-4-hydroxybenzenepropanoate;(s)-alpha-amino-4-hydroxybenzenepropanoic acid;(s)-alpha-amino-4-hydroxy-benzenepropanoate;(s)-alpha-amino-4-hydroxy-benzenepropanoic acid;2-amino-3-(4-hydroxyphen yl)-2-amino-3-(4-hydroxyphenyl)-propanoate;2-amino-3-(4-hydroxyphen yl)-2-amino-3-(4-hydroxyphenyl)-propanoic acid;3-(4-hydroxyphenyl)-l-alanine;4-hydroxy-l-phenylalanine;Benzenepropanoate;Benzenepropanoic acid;L-tyrosine;L-p-tyrosine;Tyr;Tyrosine;P-tyrosine;(2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;L-tyrosin;Y;(-)-α-amino-p-hydroxyhydrocinnamate;(-)-α-amino-p-hydroxyhydrocinnamic acid;(2s)-2-amino-3-(4-hydroxyphenyl)propanoate;(s)-α-amino-4-hydroxybenzenepropanoate;(s)-α-amino-4-hydroxybenzenepropanoic acidPW_C000103Tyr39619686201284819792470723566510756661085886105834222512348151424123184241331577051224777543417846911179046128791021327923625382189377824733781177734021177744031210011221215891241226524411226534421226554101235661351241471181252264761252274771252294441275523885584-Hydroxyphenylpyruvic acidHMDB00007074-Hydroxyphenylpyruvic acid (4-HPPA) is a keto acid that is involved in the tyrosine catabolism pathway. It is a product of the enzyme (R)-4-hydroxyphenyllactate dehydrogenase [EC 1.1.1.222] and is formed during tyrosine metabolism. The conversion from tyrosine to 4-HPPA is catalyzed by tyrosine aminotransferase. Additionally, 4-HPPA can be converted to homogentisic acid which is one of the precursors to ochronotic pigment. The enzyme 4-hydroxyphenylpyruvic acid dioxygenase (HPD) catalyzes the reaction that converts 4-hydroxyphenylpyruvic acid to homogentisic acid. A deficiency in the catalytic activity of HPD is known to lead to tyrosinemia type III, an autosomal recessive disorder characterized by elevated levels of blood tyrosine and massive excretion of tyrosine derivatives into urine. It has been shown that hawkinsinuria, an autosomal dominant disorder characterized by the excretion of 'hawkinsin,' may also be a result of HPD deficiency (PMID: 11073718). There are two isomers of HPPA, specifically 4HPPA and 3HPPA, of which 4HPPA is the most common.156-39-8C0117997915999P-HYDROXY-PHENYLPYRUVATE954DB07718OC(=O)C(=O)CC1=CC=C(O)C=C1C9H8O4InChI=1S/C9H8O4/c10-7-3-1-6(2-4-7)5-8(11)9(12)13/h1-4,10H,5H2,(H,12,13)KKADPXVIOXHVKN-UHFFFAOYSA-N3-(4-hydroxyphenyl)-2-oxopropanoic acid180.1574180.042258744-2.0824-hydroxyphenylpyruvic acid0-1FDB022193(p-hydroxyphenyl)pyruvate;(p-hydroxyphenyl)pyruvic acid;(p-hydroxyphenyl)-pyruvate;(p-hydroxyphenyl)-pyruvic acid;3-(4-hydroxyphenyl)-2-oxo-propanoate;3-(4-hydroxyphenyl)-2-oxo-propanoic acid;3-(4-hydroxyphenyl)-2-oxopropionate;3-(4-hydroxyphenyl)-2-oxopropionic acid;3-(4-hydroxyphenyl)pyruvate;3-(4-hydroxyphenyl)pyruvic acid;3-(p-hydroxyphenyl)-2-oxopropionate;3-(p-hydroxyphenyl)-2-oxopropionic acid;3-(p-hydroxyphenyl)pyruvate;3-(p-hydroxyphenyl)pyruvic acid;4-hydroxy-a-oxobenzenepropanoate;4-hydroxy-a-oxobenzenepropanoic acid;4-hydroxy-alpha-oxobenzenepropanoate;4-hydroxy-alpha-oxobenzenepropanoic acid;4-hydroxyphenylpyruvate;4hppa;Hppa;Hydroxyphenylpyruvate;Hydroxyphenylpyruvic acid;Testacid;P-hydroxyphenylpyruvic;3-(4-hydroxy-phenyl)pyruvic acid;3-(p-hydroxyphenyl)-2-oxopropanoic acid;4-hydroxy alpha-oxobenzenepropanoic acid;4-hydroxyphenylpyruvic acid;P-hydroxyphenylpyruvic acid;(4-hydroxyphenyl)pyruvate;3-(4-hydroxy-phenyl)pyruvate;3-(p-hydroxyphenyl)-2-oxopropanoate;4-hydroxy a-oxobenzenepropanoate;4-hydroxy a-oxobenzenepropanoic acid;4-hydroxy alpha-oxobenzenepropanoate;4-hydroxy α-oxobenzenepropanoate;4-hydroxy α-oxobenzenepropanoic acid;P-hydroxyphenylpyruvatePW_C0005584HPPA1287819922834322512349151770392247705525378471111791031321210041221215901241235691351241481181275533881065OxygenHMDB0001377Oxygen is the third most abundant element in the universe after hydrogen and helium and the most abundant element by mass in the Earth's crust. Diatomic oxygen gas constitutes 20.9% of the volume of air. All major classes of structural molecules in living organisms, such as proteins, carbohydrates, and fats, contain oxygen, as do the major inorganic compounds that comprise animal shells, teeth, and bone. Oxygen in the form of O2 is produced from water by cyanobacteria, algae and plants during photosynthesis and is used in cellular respiration for all living organisms. Green algae and cyanobacteria in marine environments provide about 70% of the free oxygen produced on earth and the rest is produced by terrestrial plants. Oxygen is used in mitochondria to help generate adenosine triphosphate (ATP) during oxidative phosphorylation. For animals, a constant supply of oxygen is indispensable for cardiac viability and function. To meet this demand, an adult human, at rest, inhales 1.8 to 2.4 grams of oxygen per minute. This amounts to more than 6 billion tonnes of oxygen inhaled by humanity per year. At a resting pulse rate, the heart consumes approximately 8-15 ml O2/min/100 g tissue. This is significantly more than that consumed by the brain (approximately 3 ml O2/min/100 g tissue) and can increase to more than 70 ml O2/min/100 g myocardial tissue during vigorous exercise. As a general rule, mammalian heart muscle cannot produce enough energy under anaerobic conditions to maintain essential cellular processes; thus, a constant supply of oxygen is indispensable to sustain cardiac function and viability. However, the role of oxygen and oxygen-associated processes in living systems is complex, and they and can be either beneficial or contribute to cardiac dysfunction and death (through reactive oxygen species). Reactive oxygen species (ROS) are a family of oxygen-derived free radicals that are produced in mammalian cells under normal and pathologic conditions. Many ROS, such as the superoxide anion (O2-)and hydrogen peroxide (H2O2), act within blood vessels, altering mechanisms mediating mechanical signal transduction and autoregulation of cerebral blood flow. Reactive oxygen species are believed to be involved in cellular signaling in blood vessels in both normal and pathologic states. The major pathway for the production of ROS is by way of the one-electron reduction of molecular oxygen to form an oxygen radical, the superoxide anion (O2-). Within the vasculature there are several enzymatic sources of O2-, including xanthine oxidase, the mitochondrial electron transport chain, and nitric oxide (NO) synthases. Studies in recent years, however, suggest that the major contributor to O2- levels in vascular cells is the membrane-bound enzyme NADPH-oxidase. Produced O2- can react with other radicals, such as NO, or spontaneously dismutate to produce hydrogen peroxide (H2O2). In cells, the latter reaction is an important pathway for normal O2- breakdown and is usually catalyzed by the enzyme superoxide dismutase (SOD). Once formed, H2O2 can undergo various reactions, both enzymatic and nonenzymatic. The antioxidant enzymes catalase and glutathione peroxidase act to limit ROS accumulation within cells by breaking down H2O2 to H2O. Metabolism of H2O2 can also produce other, more damaging ROS. For example, the endogenous enzyme myeloperoxidase uses H2O2 as a substrate to form the highly reactive compound hypochlorous acid. Alternatively, H2O2 can undergo Fenton or Haber-Weiss chemistry, reacting with Fe2+/Fe3+ ions to form toxic hydroxyl radicals (-.OH). (PMID: 17027622, 15765131).7782-44-7C0000797715379CPD-6641952O=OO2InChI=1S/O2/c1-2MYMOFIZGZYHOMD-UHFFFAOYSA-Ndioxygen31.998831.9898292440singlet oxygen00FDB022589Dioxygen;Molecular oxygen;O2;Oxygen;Oxygen molecule;[oo];Dioxygene;Disauerstoff;E 948;E-948;E948PW_C001065O2959110524516500185058549146252863836491067431688207541576347693383621375492016242531222803294260424747135467123548012554931265508127580910859731476129159700618870321637050160731921375332107560212839515111816216118641981188321511894211120572251206316412247286122792261232524912706291127162921300429813016300130263011303830213260223422761742657315769102937704429477214134773501117736313077377331773953327749711377512115775373347762633677723337777361127774712977756341778051147781213378070329781511327838134578805343791113601200474081203831221204264051205424071205534141205944091206014061208834151210451241211043831216054341216564291221173821225734181226893841227983741228224431230271351230603761231284471231391361231634481231761191231874501232191371232261201234594511236091181236693981241634691242144641246693991251454541252751211254254821257064781257314831257372971257404791258844811261002991262724841265224951267214891268254801269645021269862071271982091272142081272192051272225011273055041273452061275573881275745151278353891280813951280953901283125061284323911316Carbon dioxideHMDB0001967Carbon dioxide is a colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. Carbon dioxide is produced during respiration by all animals, fungi and microorganisms that depend on living and decaying plants for food, either directly or indirectly. It is, therefore, a major component of the carbon cycle. Additionally, carbon dioxide is used by plants during photosynthesis to make sugars which may either be consumed again in respiration or used as the raw material to produce polysaccharides such as starch and cellulose, proteins and the wide variety of other organic compounds required for plant growth and development. When inhaled at concentrations much higher than usual atmospheric levels, it can produce a sour taste in the mouth and a stinging sensation in the nose and throat. These effects result from the gas dissolving in the mucous membranes and saliva, forming a weak solution of carbonic acid. Carbon dioxide is used by the food industry, the oil industry, and the chemical industry. Carbon dioxide is used to produce carbonated soft drinks and soda water. Traditionally, the carbonation in beer and sparkling wine comes about through natural fermentation, but some manufacturers carbonate these drinks artificially.124-38-9C0001128016526274O=C=OCO2InChI=1S/CO2/c2-1-3CURLTUGMZLYLDI-UHFFFAOYSA-Nmethanedione44.009543.9898292440.630carbon dioxide00DBMET00423FDB014084Carbon oxide;Carbon-12 dioxide;Carbonic acid anhydride;Carbonic acid gas;Carbonic anhydride;[co2];Co2;E 290;E-290;E290;R-744PW_C001316CO25081211204448013503186403677316952080651133431638491745225511731447052831035320111575010857711015968100602615560781616471178663710769221907017160703516370611887163205730819873332137461222753021082152258223151915824911849277119081701246422612688290426263154352331876994293771221337717013277470333777391127775012977763341780771347840535678427334789413317922713080008368806751198071713594836384113291391115549121119954406120089122120155407120364412120556414120833419120922124120991408121284125121505383122744120123011446123190450123418455123489118123556374123855136124063398125344479125460297125516481125824490125870299125931482126280480126887501127052206127277507127331388127390502140798185134Oxoglutaric acidHMDB0000208Oxoglutaric acid, also known as alpha-ketoglutarate, alpha-ketoglutaric acid, AKG, or 2-oxoglutaric acid, is classified as a gamma-keto acid or a gamma-keto acid derivative. gamma-Keto acids are organic compounds containing an aldehyde substituted with a keto group on the C4 carbon atom. alpha-Ketoglutarate is considered to be soluble (in water) and acidic. alpha-Ketoglutarate is a key molecule in the TCA cycle, playing a fundamental role in determining the overall rate of this important metabolic process (PMID: 26759695). In the TCA cycle, AKG is decarboxylated to succinyl-CoA and carbon dioxide by AKG dehydrogenase, which functions as a key control point of the TCA cycle. Additionally, AKG can be generated from isocitrate by oxidative decarboxylation catalyzed by the enzyme known as isocitrate dehydrogenase (IDH). In addition to these routes of production, AKG can be produced from glutamate by oxidative deamination via glutamate dehydrogenase, and as a product of pyridoxal phosphate-dependent transamination reactions (mediated by branched-chain amino acid transaminases) in which glutamate is a common amino donor. AKG is a nitrogen scavenger and a source of glutamate and glutamine that stimulates protein synthesis and inhibits protein degradation in muscles. In particular, AKG can decrease protein catabolism and increase protein synthesis to enhance bone tissue formation in skeletal muscles (PMID: 26759695). Interestingly, enteric feeding of AKG supplements can significantly increase circulating plasma levels of hormones such as insulin, growth hormone, and insulin-like growth factor-1 (PMID: 26759695). It has recently been shown that AKG can extend the lifespan of adult C. elegans by inhibiting ATP synthase and TOR (PMID: 24828042). In combination with molecular oxygen, alpha-ketoglutarate is required for the hydroxylation of proline to hydroxyproline in the production of type I collagen. A recent study has shown that alpha-ketoglutarate promotes TH1 differentiation along with the depletion of glutamine thereby favouring Treg (regulatory T-cell) differentiation (PMID: 26420908). alpha-Ketoglutarate has been found to be associated with fumarase deficiency, 2-ketoglutarate dehydrogenase complex deficiency, and D-2-hydroxyglutaric aciduria, which are all inborn errors of metabolism (PMID: 8338207).328-50-7C0002651309152-KETOGLUTARATE50DB02926OC(=O)CCC(=O)C(O)=OC5H6O5InChI=1S/C5H6O5/c6-3(5(9)10)1-2-4(7)8/h1-2H2,(H,7,8)(H,9,10)KPGXRSRHYNQIFN-UHFFFAOYSA-N2-oxopentanedioic acid146.0981146.021523302-0.442oxoglutarate0-2FDB0033612-ketoglutarate;2-ketoglutaric acid;2-oxo-1,5-pentanedioate;2-oxo-1,5-pentanedioic acid;2-oxoglutarate;2-oxoglutaric acid;2-oxopentanedioate;2-oxopentanedioic acid;Oxoglutarate;Alpha-ketoglutaric acid;Oxoglutaric acid;A-ketoglutarate;A-ketoglutaric acid;Alpha-ketoglutarate;α-ketoglutarate;α-ketoglutaric acidPW_C000134AKG152423141414684991867331110842126351447501455261467545375103541411754381185564132600814760361556069157609216164821786530857471222751522475191518209225837422011863198126812897705425377135133774811117752311277746129779673457797034677976327779843477842533480018368806941351131629411997240612002212412008440712017412212055241412081441812098940812114642312115242412116042512275712012283111912318645012339945412355437412371845812372445912373246012535747912540029912545548112553329712580048912592948212690050112694038812699320612706620512725550612738850295L-Glutamic acidHMDB0000148Glutamic acid (Glu), also referred to as glutamate (the anion), is one of the 20 proteinogenic amino acids. It is not among the essential amino acids. Glutamate is a key molecule in cellular metabolism. In humans, dietary proteins are broken down by digestion into amino acids, which serves as metabolic fuel or other functional roles in the body. Glutamate is the most abundant fast excitatory neurotransmitter in the mammalian nervous system. At chemical synapses, glutamate is stored in vesicles. Nerve impulses trigger release of glutamate from the pre-synaptic cell. In the opposing post-synaptic cell, glutamate receptors, such as the NMDA receptor, bind glutamate and are activated. Because of its role in synaptic plasticity, it is believed that glutamic acid is involved in cognitive functions like learning and memory in the brain. Glutamate transporters are found in neuronal and glial membranes. They rapidly remove glutamate from the extracellular space. In brain injury or disease, they can work in reverse and excess glutamate can accumulate outside cells. This process causes calcium ions to enter cells via NMDA receptor channels, leading to neuronal damage and eventual cell death, and is called excitotoxicity. The mechanisms of cell death include: * Damage to mitochondria from excessively high intracellular Ca2+. * Glu/Ca2+-mediated promotion of transcription factors for pro-apoptotic genes, or downregulation of transcription factors for anti-apoptotic genes. Excitotoxicity due to glutamate occurs as part of the ischemic cascade and is associated with stroke and diseases like amyotrophic lateral sclerosis, lathyrism, and Alzheimer's disease. glutamic acid has been implicated in epileptic seizures. Microinjection of glutamic acid into neurons produces spontaneous depolarization around one second apart, and this firing pattern is similar to what is known as paroxysmal depolarizing shift in epileptic attacks. This change in the resting membrane potential at seizure foci could cause spontaneous opening of voltage activated calcium channels, leading to glutamic acid release and further depolarization. (http://en.wikipedia.org/wiki/Glutamic_acid).56-86-0C000253303216015GLT30572DB00142N[C@@H](CCC(O)=O)C(O)=OC5H9NO4InChI=1S/C5H9NO4/c6-3(5(9)10)1-2-4(7)8/h3H,1-2,6H2,(H,7,8)(H,9,10)/t3-/m0/s1WHUUTDBJXJRKMK-VKHMYHEASA-N(2S)-2-aminopentanedioic acid147.1293147.053157781-0.263L-glutamic acid0-1FDB012535(2s)-2-aminopentanedioate;(2s)-2-aminopentanedioic acid;(s)-(+)-glutamate;(s)-(+)-glutamic acid;(s)-2-aminopentanedioate;(s)-2-aminopentanedioic acid;(s)-glutamate;(s)-glutamic acid;1-amino-propane-1,3-dicarboxylate;1-amino-propane-1,3-dicarboxylic acid;1-aminopropane-1,3-dicarboxylate;1-aminopropane-1,3-dicarboxylic acid;2-aminoglutarate;2-aminoglutaric acid;2-aminopentanedioate;2-aminopentanedioic acid;Aciglut;Aminoglutarate;Aminoglutaric acid;E;Glt;Glu;Glusate;Glut;Glutacid;Glutamicol;Glutamidex;Glutaminate;Glutaminic acid;Glutaminol;Glutaton;L-(+)-glutamate;L-(+)-glutamic acid;L-glu;L-glutamate;L-glutaminate;L-glutaminic acid;L-a-aminoglutarate;L-a-aminoglutaric acid;L-alpha-aminoglutarate;L-alpha-aminoglutaric acid;A-aminoglutarate;A-aminoglutaric acid;A-glutamate;A-glutamic acid;Alpha-aminoglutarate;Alpha-aminoglutaric acid;Alpha-glutamate;Alpha-glutamic acid;Acide glutamique;Acido glutamico;Acidum glutamicum;Glutamate;Glutamic acid;L-glutaminsaeurePW_C000095Glu16244365811911384164149699110542144850145626146254532311153441135415117543911855651325631107563210858591056006147607115761919465318568381876844188709272709371716520571822077514224751815182082258373220117921981185516112004222126213112683289126972904234831542349318428453207702025377332133775251127797134677977327779813477829134580649135120023124120040122120086407120347406120692126120816418121147423121153424121157425122833119122997120123299443123401454123719458123725459123729460125401299125418297125457481125667479125769301125802489126941388126995206127162501127257506140738841407395971148Pyridoxal 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'P18232445351812214011969620111042145050145826212010215049532511154161175421103544111854551205567132558113365338570181607167205721621272222131185816112175151126233112628181268428912689290770172537703722577041293770522247752611277764341779733467797932778292345788553327886233180696135986307119912122120024124120029406120087407120817418121149423121155424122069123122076383122834119123402454123721458123727459124620447124627398125302297125402299125407479125458481125803489126224298126231495126942388126947501126996206127258506127786513127793390237794-hydroxyphenylacetate decarboxylase glycyl radical subunitQ84F16
Glycyl radical subunit of the HPA decarboxylase that decarboxylates phenylacetates with a hydroxyl group in the p-position. Active toward 4-hydroxyphenylacetate, 3,4-dihydroxyphenylacetate and to a lesser extent p-hydroxymandelate (2-hydroxy-2-(4-hydroxyphenyl)acetate), forming 4-methylphenol, 4-methylcatechol and 4-hydroxybenzylalcohol, respectively. Is likely involved in the catabolism of aromatic amino acids such as tyrosine fermentation. 4-methylphenol (p-cresol) formation provides metabolic toxicity, which may benefit the pathogen C.difficile by suppression of the endogenous gastrointestinal microflora, allowing the development of gastrointestinal infections (PubMed:11231288, PubMed:16878993). The large subunit is the catalytic subunit that binds the substrate (By similarity).
hpdB2094.1.1.83140950184140951214611731114613816810207UnknownUnknown12.3.1.85; 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.-640410642931643453916617917049182221167831168521212481212914121332291359735113617871400203081401567681405763091405898321408646014093348140954184141261831141275877141432931141584958141585959141586828142155261421941514226537214233223142671291426739961426839731428137871432728111432735214335575143398106514347411431434761314347896114351511481439341168143951118414395981014409423114412231114423142144246121914428490145624145214562714541456788171457491212145776847145834761459527891460595023780ABC transporter, substrate-binding lipoproteinC9YJQ5CDR20291_0805210144392102714450630814465753144699261447298241457471211145748121214581152271Tyrosine aminotransferaseP17735
Transaminase involved in tyrosine breakdown. Converts tyrosine to p-hydroxyphenylpyruvate. Can catalyze the reverse reaction, using glutamic acid, with 2-oxoglutarate as cosubstrate (in vitro). Has much lower affinity and transaminase activity towards phenylalanine.
HMDBP00277TAT16q22.1X5251812.6.1.5128181993214106918414419926146115311146136168277Aspartate aminotransferase, cytoplasmicP17174Plays a key role in amino acid metabolism (By similarity).
HMDBP00283GOT110q24.1-q25.1BC00049812.6.1.1; 2.6.1.3712819952141826261431431150154-hydroxyphenylacetate decarboxylase1PW_P015015250472377915021p-hydroxyphenylpyruvate oxidase1PW_P015021250531020715016ABC transporter 1PW_P015016250482378014972Unknown1PW_P0149722499510207357Tyrosine aminotransferase1PW_P000357378271216311481203Aspartate aminotransferase, cytoplasmic1PW_P00020322127729211481213941PW_R213941Right822600131Compoundfalse82260112321Compoundfalse203544150154.1.1.83213946PW_R213946Right8226145581Compoundfalse82261510651Compoundfalse822616131Compoundfalse82261713162Compoundfalse203549150212.3.1.85213955PW_R213955Right8226341031Compoundfalse82263512321Compoundfalse80falsePW_R000080Both3111031Compoundfalse3121341Compoundtrue3135581Compoundfalse314951Compoundtrue4403572.6.1.520849020311191PW_T0111911159812321Compound5160Left11194PW_T011194116011031Compound260Left2331150162021-03-02T14:13:20-07:002021-03-02T14:13:20-07:001411195PW_T011195116021031Compound160Right11316PW_T0113161172312321Compound18460Right2423149722021-04-12T16:31:14-06:002021-04-12T16:31:14-06:00372309803413281false3060153110regular2001903098035123218481false3055186110regular2001903098038103281false305671810regular2001903098039558281false3056115310regular20019030980411065265false2978132910regular787830980421316252false2977145710regular7878309804312325181false1010166910regular200190309804412326081false1680116410regular20019030980451036081false351172310regular200190309807510381false167560910regular2001903098078103181false1743281regular200190309807910360156false12095931regular100100309987612326081false3500186110regular200190310039713418481false284682810regular20019031003989518481false2846103810regular200190310039911481849false311198820regular1003511960052377922false308017518subunitregular1507011960081020722false308113978proteinregular1507011960092378076false33317788subunitregular1507011969601020776false331019218subunitregular1507011971522711846false30769938subunitregular16080940403150151152692119104411960059404061502111526921191047119600894040715016115269119104811960099411191497211526911919641196960941309357115269184119215611971524078331003994229437Cofactor4225912M3160 1721 C3160 1751 3155 1721 3155 1751 5false184225913M3155 1861 C3155 1831 3155 1851 3155 1821 5false18trueM 25.946855044164835 762.9282433080148 L 11 761.6666870117188 L 17.380887721185843 775.2418213347971false4225919M3156 1343 C3156 1373 3156 1367 3156 1397 5false184225920M3056 1368 C3089 1368 3156 1367 3156 1397 5false184225921M3160 1531 C3160 1501 3156 1497 3156 1467 5false18trueM 110.94685504416483 834.9282433080148 L 96 833.6666870117188 L 102.38088772118584 847.2418213347971false4225922M3055 1496 C3085 1496 3156 1497 3156 1467 5false18trueM 110.94685504416483 834.9282433080148 L 96 833.6666870117188 L 102.38088772118584 847.2418213347971false4225923M1110 1669 C1110 1635 1100 1294 1100 1265 C1188 1263 1606 1261 1680 1259 83false18trueM 1250.9468550441647 1122.9281822728585 L 1236 1121.6666259765625 L 1242.380887721186 1135.2417602996409false4225924M1680 1259 C1650 1259 2297 1404 2267 1404 83true184225925M3256 813 C3286 813 3301 813 3331 813 83false18trueM 487.6135115383055 476.261556296296 L 472.6666564941406 475 L 479.04754421532647 488.5751343230783false4225926M3511 818 C3481 818 3511 813 3481 813 83false184225963M1775 799 C1775 829 2965 1179 2965 1209 5true184225964M1780 1164 C1780 1134 1775 829 1775 799 5false3trueM 1285.6134810207272 999.5948692845773 L 1270.6666259765625 998.3333129882812 L 1277.0475136977484 1011.9084473113596false4225969M374 423 C411 423 2934 334 2964 334 83true184225970M1775 609 C1775 579 1774 452 1774 422 C1722 421 421 423 374 423 83false18trueM 1194.9468550441647 96.92822041983119 L 1180 95.66666412353516 L 1186.380887721186 109.2417984466135false4225971M1110 1859 C1109 1899 1510 1909 1540 1909 5false18trueM 868.0644009829867 1644.2781440706694 L 883 1645.6666259765625 L 876.7346610946918 1632.0377768541446false4225972M1110 1859 C1109 1936 1306 2144 1535 2144 5false18trueM 915.397713971268 1778.2781440706694 L 930.3333129882812 1779.6666259765625 L 924.067974082973 1766.0377768541446false4228662M3255 1956 C3285 1956 3280 1956 3310 1956 83false184228663M3500 1956 C3470 1956 3490 1956 3460 1956 83false18trueM 229.61352679709452 1178.9281822728585 L 214.6666717529297 1177.6666259765625 L 221.04755947411553 1191.2417602996409false4229433M3156 908 C3156 938 3156 963 3156 993 5false18trueM 160.94685504416483 713.5948692845773 L 146 712.3333129882812 L 152.38088772118584 725.9084473113596false4229434M3046 923 C3087 923 3156 963 3156 993 5false18trueM 160.94685504416483 713.5948692845773 L 146 712.3333129882812 L 152.38088772118584 725.9084473113596false4229435M3156 1153 C3156 1123 3156 1103 3156 1073 5false18trueM 160.94685504416483 713.5948692845773 L 146 712.3333129882812 L 152.38088772118584 725.9084473113596false4229436M3046 1133 C3089 1133 3156 1103 3156 1073 5false18trueM 160.94685504416483 713.5948692845773 L 146 712.3333129882812 L 152.38088772118584 725.9084473113596false4229437M1621 688 L1621 738 L1671 688 z10true184229438M1110 1859 C1108 2063 1453 2363 1540 2364 5false18trueM 765.397713971268 1716.2781440706694 L 780.3333129882812 1717.6666259765625 L 774.067974082973 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