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Showing 61 - 70 of 48701 pathways
SMPDB ID Pathway Chemical Compounds Proteins

SMP0000035

Pw000145 View Pathway
Metabolic

Bile Acid Biosynthesis

A bile acids life begins as cholesterol is catabolized, as bile acid is a derivative of cholesterol. This pathway occurs in the liver, beginning with cholesterol being converted to 7a-hydroxycholesterol through the enzyme cholesterol-7-alpha-monooxygenase, after being transported into the liver cell. 7a-hydroxycholesterol then becomes 7a-hydroxy-cholestene-3-one, which is made possible by the enzyme 3-beta-hydroxysteroid dehydrogenase type 7. 7a-hydroxy-cholestene-3-one then is used in two different chains of reactions. The first, continuing in the liver, uses the enzyme 3-oxo-5-beta-steroid-4-deydrogenase to become 7a-hydroxy-5b-cholestan-3-one. After that, aldo-keto reductase family 1 member C4 is used to create 3a,7a-dihydroxy-5b-cholestane. In the mitochondria of the cell, sterol 26-hydroxylase converts 3a,7a-dihydroxy-5b-cholestane to 3a,7a,26-trihydroxy-5b-cholestane, which is then converted to 3a,7a-dihydroxy-5b-cholestan-26-al by the same enzyme used in the previous reaction. This enzyme is used another time, to create 3a,7a-dihydroxycoprostanic acid. Then, bile acyl-CoA synthetase teams up with 3a,7a-dihydroxycoprostanic acid to create 3a,7a-dihydroxy-5b-cholestanoyl-CoA. 3a,7a-dihydroxy-5b-cholestanoyl-CoA remains intact while alpha-methylacyl-CoA racemase moves it along through the peroxisome. Peroxisomal acyl coenzyme A oxidase 2 converts 3a,7a-dihydroxy-5b-cholestanoyl-CoA into 3a,7a-dihydoxy-5b-cholest-24-enoyl-CoA. With the help of water, peroxisomal multifunctional enzyme type 2 turns 3a,7a-dihydoxy-5b-cholest-24-enoyl-CoA into 3a,7a,24-trihydoxy-5b-cholestanoyl-CoA. This compound then uses peroxisomal multifunctional enzyme type 2 to create chenodeoxycholoyl-CoA. From there, propionyl-CoA and chenodeoxycholoyl-CoA join forces and enlist the help of non-specific lipid transfer protein to further chenodeoxycholoyl-CoAâ€TMs journey in the peroxisome. It is then transported back into intracellular space, where after its used in 3 different reactions, its derivatives interact with intestinal microflora in the extracellular space to become lithocholyltaurine, lithocholic acid glycine conjugate, and lithocholic acid. Revisiting 7a-hydroxy-cholestene-3-one, the second chain of reactions it is involved in follows a similar path as the first, moving through the mitochondria, endoplasmic reticulum and peroxisome until choloyl-CoA is formed, which then is used in three reactions so that its derivatives may leave the cell to interact with intestinal microflora and become taurodeoxycholic acid, deoxycholic acid glycine conjugate and deoxycholic acid. There are two more important components of this pathway, both depicting the breakdown of cholesterol into bile acid. These components of the pathway occur in the endoplasmic reticulum membrane, although 2 enzymes, 25-hydroxycholesterol 7-alpha-hydroxylase and sterol 26 hydroxylase, are found in the mitochondria. Bile acids play a very important part in the digestion of foods, and are responsible for the absorption of water soluble vitamins in the small intestine. Bile acids also help absorb fats into the small intestine, a crucial part of any vertebrates diet.

SMP0000005

Pw000140 View Pathway
Metabolic

Pterine Biosynthesis

Folates are very important cofactors that provide support for many biosynthetic reactions. The reactions depicted in this pathway include reactions that are paired with transports, within the cell, travelling intracellularly, which allows folate to be absorbed by cells, as well as the synthesis of pterines, which are used in folate synthesis. Two branches are depicted: Pterin synthesis and Folate biosynthesis. In pterin synthesis, GTP is the precursor for pterin biosynthesis. In the first reaction, GTP cyclohydrolase acts to create formamidopyrimidine nucleoside triphosphate from guanosine triphosphate, which is provided from the purine metabolism pathway. Formamidopyrimidine nucleoside triphosphate then uses GTP cyclohydrolase again to create 2,5-diaminopyrimidine nucleoside triphosphate. GTP cyclohydrolase then works with 2,5-diaminopyrimidine nucleoside triphosphate to produce 2,3-diamino-6-(5’-triphosphoryl-3’,4’-trihydroxy-2’-oxopentyl)-amino-4-oxopyrimidine, which is then converted by GTP cyclohydrolase to dihydroneopterin triphosphate. Dihydroneopterin is then transported to the mitochondria and subsequently catalyzed into dyspropterin, which then exits the mitochondria to continue pterin biosynthesis. Once having been transported from the mitochondria, dyspropterin uses sepiapterin reductase, aldose reductase and carbonyl reductase [NADPH] 1 to create 6-lactoyltetrahydropterin. This compound then undergoes 2 reactions, the first being sepiapterin reductase converting 6-lactoyltetrahydropterin into tetrahydrobiopterin, the second being 6-lactoyltetrahydropterin being converted to sepiapterin. Both branches of pterin reactions then respectively end in the creation of neopterin and dihydrobiopterin.

SMP0000074

Pw000164 View Pathway
Metabolic

Retinol Metabolism

Retinol is part of the vitamin A family, and is known as vitamin A1, and in a dietary context it is a type of preformed vitamin A. As with other preformed vitamin A's, it can be obtained from animal sources, with the highest concentrations coming from animal liver, with other sources being fish and dairy products. Other forms of vitamin A include retinal, its aldehyde form, retinoic acid, its acid form, and reinyl ester, its ester form. Additionally, herbivores and omnivores can obtain provitamin A from things such as alpha-, beta- and gamma-carotene, which can be converted to retinol as needed by the body. Retinol can be used in the body to form retinyl ester via diacylglycerol O-acyltransferase 1 and acyl-CoA wax akcohol acyltransferase 1 which both use acetyl-CoA as a reactant and produce CoA in addition to the retinyl ester. IT can also be produced by lecithin retinol acyltransferase, which uses a phosphatidylcholine molecule, and produces glycerophosphocholine. All of these reactions take place in the endoplasmic reticulum. Retinyl ester can also be converted back to retinol by patatin-like phospholipase domain-containing protein 4 as the enzyme in a reaction that also converts a diacylglycerol to a triacylglycerol. Alternately, retinyl ester can interact with retinoid isomerohydrolase to form 11-cis-retinol. 11-cis-retinol can be converted to retinyl palmitate by either diacylglycerol O-acyltransferase 1 or acyl-CoA wax alcohol acyltransferase 1 in the endoplasmic reticulum, which both add the acetyl group onto 11-cis-retinol, forming CoA as a side product. Alternatively, retinyl palmitate can be formed by lecithin retinol acyltransferase, which takes a molecule of phosphatidylcholine, and produces glycerophosphocholine in addition to the retinyl palmitate. Rhodopsin, a photosensitive protein found in the retina, can be converted to bathorhodopsin, which has previously been known as prelumirhodopsin. This conversion is caused by the absorption of light into the retinal portion of the protein complex, which then isomerizes, forcing the protein to change shape to accomodate this. Bathorhodopsin almost immediately converts to lumirhodopsin, which then converts to metarhodopsin, and at this point, the retinal is in its all-trans configuration. All-trans retinal can also be formed from 11-cis-retinaldehyde, also known as 11-cis-retinal, via dehydrogenase/reductase SDR family member 4 or retinol dehydrogenase 12 in the cell, as well as retinol dehydrogenases 8 and 16, short-chain dehydrogenase/reductase 3 or dehydrogenase/reductase SRD family member 9 in the endoplasmic reticulum. Two molecules of retinal can also be formed from beta-carotene, after its interaction with betabeta-carotene 15,15'-monooxygenase, or from retinol via retinol dehydrogenase 11 in the endoplasmic reticulum. Additionally, 11-cis-retinaldehyde can reversibly form all-trans retinal via interaction with alcohol dehydrogenase 1A. 11-cis-retinaldehyde is also in the conformation found in rhodopsin, and can be used to create more rhodopsin complexes. 11-cis-retinaldehyde can also be converted to 11-cis-retinol by retinol dehydrogenase in the endoplasmic reticulum. Retinol can also isomerize and form 9-cis-retinol, which can then be reversibly oxidized to form 9-cis-retinal by interacting with either retinol dehydrogenase 11 or dehydrogenase/reductase SDR family member 4. 9-cis-retinal can then be further oxidized to 9-cis-retinoic acid by retinal dehydrogenase 1 or 2. 9-cis-retinoic acid can also be formed from the isomerization of all-trans retinoic acid, which in turn is formed by the oxidation of retinol by either of retinal dehydrogenase 1 or 2. All-trans retinoic acid can also be glucuronidated to form retinoyl b-glucuronide, in a reaction catalyzed by a multiprotein chaperone complex including UDP-glucuronosyltransferase 1-1 in the endoplasmic reticulum. Finally, in the endoplasmic reticulum, all-trans-retinoic acid can undergo epoxidation to form all-trans-5,6-epoxyretinoic acid by interaction with a complex of cytochrome P450 proteins, or hydroxylated to either 4-hydroxyretinoic acid or all-trans-18-hydroxyretinoic acid by cytochrome P450 26A1. In one last reqction, 4-hydroxyretinoic acid can be oxidized once again by cytochrome P450 26A1 to form 4-oxo-retinoic acid.

SMP0000033

Pw000056 View Pathway
Metabolic

Methionine Metabolism

Methionine metabolism is a process that is necessary for humans. Methionine metabolism in mammals happens within two pathways, a methionine cycle and a transsulfuration sequence. These pathways have three common reactions with both pathways including the transformation of methionine to S-adenosylmethionine (SAM), the use of SAM in many different transmethylation reactions resulting in a methylated product plus S-adenosylhomocysteine, and the conversion of S-adenosylhomocysteine to produce the compounds homocysteine and adenosine. The reactions mentioned above not only produce cysteine, they also create a-ketobutyrate. This compound is then converted to succinyl-CoA through a three step process after being converted to propionyl-CoA. If the amino acids cysteine and methionine are available in enough quantity, the pathway will accumulate SAM and this will in turn encourage the production of cysteine and a-ketobutyrate, which are both glucogenic, through cystathionine synthase. When there is a lack of methionine, there is a decrease in the production of SAM, which limits cystathionine synthase activity.

SMP0000468

Pw000020 View Pathway
Metabolic

Degradation of Superoxides

Reactive oxygen species (ROS) are formed by the normal metabolic process of oxygen. Examples are superoxide, oxygen ions and peroxides and can be of either organic or inorganic origin. ROS are highly reactive due to unpaired valence shell electrons, and can cause serious damage to cells and cell organelles. The environment also may cause ROS to form, from sources such as drought, air pollutants, UV light, cold temperatures, and external chemicals. An organic example of ROS being formed is during the beta oxidation of fatty acids, or photorespiration in photosynthetic organisms. Aerobic organisms who produce energy through the electron transport chain in mitochondria produce ROS as a byproduct. ROS damage commmonly includes DNA damage, lipid peroxidation, oxidation of amino acids in proteins, and oxidatively inactivating enzymes by oxidation of cofactors. Most aerobic organisms have adapted to this dangerous condition of life, and have a system of enzymes and scavenging free radicals. Enzymes such as are essential for defense against ROS, and include superoxide dismutases (SODs) and hydroperoxidase (CAT). Superoxide dismutases are the primary method of disposal of ROS, and convert superoxide radicals to hydrogen peroxide and water. Catalase attacks the hydrogen peroxide produced by SODs, and converts it into oxygen and water. In skin cells, 5,6 dihydroxyindole-2-carboxylic acid oxidase in the melanosome membranes breaks down hydrogen peroxide into water and oxygen.

SMP0000004

Pw000157 View Pathway
Metabolic

Glycine and Serine Metabolism

This pathway describes the synthesis and breakdown of several small amino acids, including glycine, serine, and cysteine. All of these compounds share common intermediates and almost all can be biosynthesized from one another. Serine and glycine are not essential amino acids and can be synthesized from several routes. On the other hand, cysteine is a conditionally essential amino acid, meaning that it can be endogenously synthesized but insufficient quantities may be produced due to certain diseases or conditions. Serine is central to the synthesis and breakdown of the other two amino acids. Serine can be synthesized via glycerate, which can be converted into glycerate 3-phosphate (via glycerate kinase), which in turn is converted into phosphohydroxypyruvate by phosphoglycerate dehydrogenase and then phosphoserine (via phosphoserine transaminase) and finally to serine (via phosphoserine phosphatase). The serine synthesized via this route can be used to create cysteine and glycine through the homocysteine cycle. In the homocysteine cycle, cystathionine beta-synthase catalyzes the condensation of homocysteine and serine to give cystathionine. Cystathionine beta-lyase then converts this double amino acid to cysteine, ammonia, and alpha-ketoglutarate. Glycine is biosynthesized in the body from the amino acid serine. In most organisms, the enzyme serine hydroxymethyltransferase (SHMT) catalyzes this transformation using tetrahydrofolate (THF), leading to methylene THF and glycine. Glycine can be degraded via three pathways. The predominant pathway in animals involves the glycine cleavage system, also known as the glycine decarboxylase complex or GDC. This system is usually triggered in response to high concentrations of glycine. The system is sometimes referred to as glycine synthase when it runs in the reverse direction to produce glycine. The glycine cleavage system consists of four weakly interacting proteins: T, P, L and H-proteins. The glycine cleavage system leads to the degradation of glycine into ammonia and CO2. In the second pathway, glycine is degraded in two steps. The first step in this degradation pathway is the reverse of glycine biosynthesis from serine with serine hydroxymethyltransferase (SHMT). The serine generated via glycine is then converted into pyruvate by the enzyme known as serine dehydratase. In the third route to glycine degradation, glycine is converted into glyoxylate by D-amino acid oxidase. Glyoxylate is then oxidized by hepatic lactate dehydrogenase into oxalate in an NAD+-dependent reaction.

SMP0000032

Pw000051 View Pathway
Metabolic

Valine, Leucine, and Isoleucine Degradation

Valine, isoleuciine, and leucine are essential amino acids and are identified as the branched-chain amino acids (BCAAs). The catabolism of all three amino acids starts in muscle and yields NADH and FADH2 which can be utilized for ATP generation. The catabolism of all three of these amino acids uses the same enzymes in the first two steps. The first step in each case is a transamination using a single BCAA aminotransferase, with α-ketoglutarate as the amine acceptor. As a result, three different α-keto acids are produced and are oxidized using a common branched-chain α-keto acid dehydrogenase (BCKD), yielding the three different CoA derivatives. Isovaleryl-CoA is produced from leucine by these two reactions, alpha-methylbutyryl-CoA from isoleucine, and isobutyryl-CoA from valine. These acyl-CoA’s undergo dehydrogenation, catalyzed by three different but related enzymes, and the breakdown pathways then diverge. Leucine is ultimately converted into acetyl-CoA and acetoacetate; isoleucine into acetyl-CoA and succinyl-CoA; and valine into propionyl-CoA (and subsequently succinyl-CoA). Under fasting conditions, substantial amounts of all three amino acids are generated by protein breakdown. In muscle, the final products of leucine, isoleucine, and valine catabolism can be fully oxidized via the citric acid cycle; in the liver, they can be directed toward the synthesis of ketone bodies (acetoacetate and acetyl-CoA) and glucose (succinyl-CoA). Because isoleucine catabolism terminates with the production of acetyl-CoA and propionyl-CoA, it is both glucogenic and ketogenic. Because leucine gives rise to acetyl-CoA and acetoacetyl-CoA, it is classified as strictly ketogenic.

SMP0121131

Pw122411 View Pathway
Metabolic

2-Amino-3-Carboxymuconate Semialdehyde Degradation

This pathway is part of a major route of the degradation of L-tryptophan. It begins with 2-amino-3-carboxymuconate-6-semialdehyde which is generated from L-tryptophan degradation. The 2-amino-3-carboxymuconate-6-semialdehyde first is acted upon by a decarboxylase, forming 2-aminomuconic acid semialdehyde, which is then dehydrogenated by 2-aminomuconic semialdehyde dehydrogenase to form 2-aminomuconic acid. An unknown protein forms a 2-aminomuconate deaminase which forms (3E)-2-oxohex-3-enedioate, and a second unknown protein forms a 2-aminomuconate reductase, which forms oxoadipic acid from (3E)-2-oxohex-3-enedioate. Finally, within the mitochondria, oxoadipic acid is dehydrogenated and a coenzyme A is attached by the organelle’s oxoglutarate dehydrogenase complex, forming glutaryl-CoA. Glutaryl-CoA can then be further degraded.

SMP0000027

Pw000032 View Pathway
Metabolic

Pantothenate and CoA Biosynthesis

Pantothenate, also called vitamin B5, is a nutrient that everyone requires in their diet. The nutrient gets its name from the greek word “pantothen” which means “from everywhere.” The reason it is called this is because pantothenic acid is found in almost every food. It is a precursor of coenzyme A, which is an essential part of many reactions in the body, specifically important in the production of compounds like cholesterol and different fatty acids. Most of pantothenic acid is found in food as phosphopentetheine or coenzyme A. Pantothenic acid, pantetheine 4’-phosphate and pantetheine are all found in red blood cells. The 6 step process in which coenzyme A is created begins with the creation of pantothenic acid from pantetheine, which is catalyzed by the enzyme pantetheinase. Pantothenic acid then works with pantothenate kinase 1 to produce D-4’-phosphopantothenate. This compound quickly becomes 4’phosphopantothenoylcysteine through the enzyme phosphopantothenate-cysteine ligase. 4’phosphopantothenoylcysteine then uses phosphopantothenoylcysteine decarboxylase to create pantetheine 4’-phosphate. This compound then undergoes two reactions, both resulting in the production of dephospho-CoA; the first reaction uses ectonucleotide pyrophosphatase/phosphodiesterase family member 1, the second uses bifunctional coenzyme A synthase. In the final step of coenzyme A synthesization, bifunctional coenzyme A synthase catalyzes dephospho-CoA into coenzyme A.

SMP0029731

Pw030608 View Pathway
Metabolic

Phosphatidylethanolamine Biosynthesis

Phosphatidylethanolamines (PE) are the second most abundant phospholipid in eukaryotic cell membranes, and contrary to phosphatidylcholine, it is concentrated with phosphatidylserine in the cell membrane's inner leaflet. In Homo sapiens, there exist two phosphatidylethanolamine biosynthesis pathways. In the visualization, all enzymes that are dark green in colour are membrane-localized. The first pathway synthesizes phosphatidylethanolamine from ethanolamine via the Kennedy pathway. First, the cytosol-localized enzyme choline/ethanolamine kinase catalyzes choline to convert to phosphocholine. Second, choline-phosphate cytidylyltransferase, localized to the endoplasmic reticulum membrane, catalyzes phosphocholine to convert to CDP-choline. Last, choline/ethanolaminephosphotransferase catalyzes phosphatidylcholine biosynthesis from CDP-choline. It requires either magnesium or manganese ions as cofactors. Phosphatidylethanolamine is also synthesized from phosphatidylserine at the mitochondrial inner membrane by phosphatidylserine decarboxylase. Phosphatidylserine, itself, is synthesized using a base-exchange reaction with phosphatidylcholine. This reaction is catalyzed by phosphatidylserine synthase which is located in the endoplasmic reticulum membrane.
Showing 61 - 70 of 48701 pathways