Browsing Pathways

The biosynthesis of Valine and L-leucine from pyruvic acid starts with pyruvic acid interacting with a hydrogen ion through a acetolactate synthase / acetohydroxybutanoate synthase resulting in a release of a carbon dioxide, a (S)-2-acetolactate. The latter compound then interacts with a hydrogen ion through a NADPH-driven acetohydroxy acid isomeroreductase resulting in the release of a NADP, a (R) 2,3-dihydroxy-3-methylvalerate. The latter compound is then dehydrated by a dihydroxy acid dehydratase resulting in the release of a water molecule an 3-methyl-2-oxovaleric acid. The 3-methyl-2-oxovaleric acid can produce an L-valine by interacting with a L-glutamic acid through a Valine Transaminase resulting in the release of a Oxoglutaric acid and a L-valine. The 3-methyl-2-oxovaleric acid then interacts with an acetyl-CoA and a water molecule through a 2-isopropylmalate synthase resulting in the release of a hydrogen ion, a Coenzyme A and a 2-Isopropylmalic acid. The isopropylimalic acid is then hydrated by interacting with a isopropylmalate isomerase resulting in a 3-isopropylmalate. This compound then interacts with an NAD driven 3-isopropylmalate dehydrogenase resulting in a NADH, a hydrogen ion and a 2-isopropyl-3-oxosuccinate. The latter compound then interacts with hydrogen ion spontaneously resulting in a carbon dioxide and a ketoleucine. The ketoleucine then interacts with a L-glutamic acid through a branched-chain amino-acid aminotransferase resulting in the oxoglutaric acid and L-leucine.

Histidine biosynthesis starts with a product of PRPP biosynthesis pathway, phosphoribosyl pyrophosphate which interacts with a hydrogen ion through an ATP phosphoribosyltransferase resulting in an pyrophosphate and a phosphoribosyl-ATP. The phosphoribosyl-ATP interacts with water through a phosphoribosyl-AMP cyclohydrolase / phosphoribosyl-ATP pyrophosphatase resulting in the release of pyrophosphate, hydrogen ion and a phosphoribosyl-AMP. The same enzyme proceeds to interact with phosphoribosyl-AMP and water resulting in a 1-(5'-Phosphoribosyl)-5-amino-4-imidazolecarboxamide. The product is then isomerized by a N-(5'-phospho-L-ribosyl-formimino)-5-amino-1-(5'-phosphoribosyl)-4-imidazolecarboxamide isomerase resulting in a PhosphoribosylformiminoAICAR-phosphate, which reacts with L-glutamine through an imidazole glycerol phosphate synthase resulting in a L-glutamic acid, hydrogen ion, 5-aminoimidazole-4-carboxamide and a D-erythro-imidazole-glycerol-phosphate. D-erythro-imidazole-glycerol-phosphate reacts with a imidazoleglycerol-phosphate dehydratase / histidinol-phosphatase, dehydrating the compound and resulting in a imidazole acetol-phosphate. Next, imidazole acetol-phosphate reacts with L-glutamic acid through a histidinol-phosphate aminotransferase, releasing oxoglutaric acid and L-histidinol-phosphate. The latter compound interacts with water and a imidazoleglycerol-phosphate dehydratase / histidinol-phosphatase resulting in L-histidinol and phosphate. L-histidinol interacts with a NAD-driven histidinol dehydrogenase resulting in a Histidinal. Histidinal in turn reacts with water in a NAD driven histidinal dehydrogenase resulting in L-Histidine. L-Histidine then represses ATP phosphoribosyltransferase, regulation its own biosynthesis.

PreQ0 or 7-cyano-7-carbaguanine is biosynthesized by degrading GTP. GTP first interacts with water through a GTP cyclohydrolase resulting in the release of a formate, a hydrogen ion and a 7,8-dihydroneopterin 3'-triphosphate. The latter compound then interacts with water through a 6-carboxy-5,6,7,8-tetrahydropterin synthase resulting in a acetaldehyde, triphosphate, 2 hydrogen ion and 6-carboxy-5,6,7,8-tetrahydropterin. The latter compound then reacts spontaneously with a hydrogen ion resulting in the release of a ammonium molecule and a 7-carboxy-7-deazaguanine. This compound then interacts with ATP and ammonium through 7-cyano-7-deazaguanine synthase resulting in the release of water, phosphate, ADP, hydrogen ion and a 7-cyano-7-carbaguanine. The degradation of 7-cyano-7-deazaguanine can lead to produce a preQ1 or a queuine by reacting with 3 hydrogen ions and 2 NADPH through a 7-cyano-7-deazaguanine reductase. PreQ1 then interacts with a guanine 34 in tRNA through a tRNA-guanine transglycosylase resulting in a release of a guanine and a 7-aminomethyl-7-deazaguanosine 34 in tRNA. This nucleic acid then interacts with SAM through a S-adenosylmethionine tRNA ribosyltransferase-isomerase resulting in a release of a hydrogen ion, L-methionine, adenine and an epoxyqueuosine

Cardiolipin (CL) is an important component of the inner mitochondrial membrane where it constitutes about 20% of the total lipid composition. It is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism (Wikipedia). Cardiolipin biosynthesis occurs mainly in the mitochondria, but there also exists an alternative synthesis route for CDP-diacylglycerol that takes place in the endoplasmic reticulum. This second route may supplement this pathway. All membrane-localized enzymes are coloured dark green in the image. First, dihydroxyacetone phosphate (or glycerone phosphate) from glycolysis is used by the cytosolic enzyme glycerol-3-phosphate dehydrogenase [NAD(+)] to synthesize sn-glycerol 3-phosphate. Second, the mitochondrial outer membrane enzyme glycerol-3-phosphate acyltransferase esterifies an acyl-group to the sn-1 position of sn-glycerol 3-phosphate to form 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid or LPA). Third, the enzyme 1-acyl-sn-glycerol-3-phosphate acyltransferase converts LPA into phosphatidic acid (PA or 1,2-diacyl-sn-glycerol 3-phosphate) by esterifying an acyl-group to the sn-2 position of the glycerol backbone. PA is then transferred to the inner mitochondrial membrane to continue cardiolipin synthesis. Fourth, magnesium-dependent phosphatidate cytidylyltransferase catalyzes the conversion of PA into CDP-diacylglycerol. Fifth, CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase synthesizes phosphatidylglycerophosphate (PGP). Sixth, phosphatidylglycerophosphatase and protein-tyrosine phosphatase dephosphorylates PGP to form phosphatidylglycerol (PG). Last, cardiolipin synthase catalyzes the synthesis of cardiolipin by transferring a phosphatidyl group from a second CDP-diacylglycerol to PG. It requires a divalent metal cation cofactor.

Cardiolipin (CL) is an important component of the inner mitochondrial membrane where it constitutes about 20% of the total lipid composition. It is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism (Wikipedia). Cardiolipin biosynthesis occurs mainly in the mitochondria, but there also exists an alternative synthesis route for CDP-diacylglycerol that takes place in the endoplasmic reticulum. This second route may supplement this pathway. All membrane-localized enzymes are coloured dark green in the image. First, dihydroxyacetone phosphate (or glycerone phosphate) from glycolysis is used by the cytosolic enzyme glycerol-3-phosphate dehydrogenase [NAD(+)] to synthesize sn-glycerol 3-phosphate. Second, the mitochondrial outer membrane enzyme glycerol-3-phosphate acyltransferase esterifies an acyl-group to the sn-1 position of sn-glycerol 3-phosphate to form 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid or LPA). Third, the enzyme 1-acyl-sn-glycerol-3-phosphate acyltransferase converts LPA into phosphatidic acid (PA or 1,2-diacyl-sn-glycerol 3-phosphate) by esterifying an acyl-group to the sn-2 position of the glycerol backbone. PA is then transferred to the inner mitochondrial membrane to continue cardiolipin synthesis. Fourth, magnesium-dependent phosphatidate cytidylyltransferase catalyzes the conversion of PA into CDP-diacylglycerol. Fifth, CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase synthesizes phosphatidylglycerophosphate (PGP). Sixth, phosphatidylglycerophosphatase and protein-tyrosine phosphatase dephosphorylates PGP to form phosphatidylglycerol (PG). Last, cardiolipin synthase catalyzes the synthesis of cardiolipin by transferring a phosphatidyl group from a second CDP-diacylglycerol to PG. It requires a divalent metal cation cofactor.

Cardiolipin (CL) is an important component of the inner mitochondrial membrane where it constitutes about 20% of the total lipid composition. It is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism (Wikipedia). Cardiolipin biosynthesis occurs mainly in the mitochondria, but there also exists an alternative synthesis route for CDP-diacylglycerol that takes place in the endoplasmic reticulum. This second route may supplement this pathway. All membrane-localized enzymes are coloured dark green in the image. First, dihydroxyacetone phosphate (or glycerone phosphate) from glycolysis is used by the cytosolic enzyme glycerol-3-phosphate dehydrogenase [NAD(+)] to synthesize sn-glycerol 3-phosphate. Second, the mitochondrial outer membrane enzyme glycerol-3-phosphate acyltransferase esterifies an acyl-group to the sn-1 position of sn-glycerol 3-phosphate to form 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid or LPA). Third, the enzyme 1-acyl-sn-glycerol-3-phosphate acyltransferase converts LPA into phosphatidic acid (PA or 1,2-diacyl-sn-glycerol 3-phosphate) by esterifying an acyl-group to the sn-2 position of the glycerol backbone. PA is then transferred to the inner mitochondrial membrane to continue cardiolipin synthesis. Fourth, magnesium-dependent phosphatidate cytidylyltransferase catalyzes the conversion of PA into CDP-diacylglycerol. Fifth, CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase synthesizes phosphatidylglycerophosphate (PGP). Sixth, phosphatidylglycerophosphatase and protein-tyrosine phosphatase dephosphorylates PGP to form phosphatidylglycerol (PG). Last, cardiolipin synthase catalyzes the synthesis of cardiolipin by transferring a phosphatidyl group from a second CDP-diacylglycerol to PG. It requires a divalent metal cation cofactor.

Cardiolipin (CL) is an important component of the inner mitochondrial membrane where it constitutes about 20% of the total lipid composition. It is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism (Wikipedia). Cardiolipin biosynthesis occurs mainly in the mitochondria, but there also exists an alternative synthesis route for CDP-diacylglycerol that takes place in the endoplasmic reticulum. This second route may supplement this pathway. All membrane-localized enzymes are coloured dark green in the image. First, dihydroxyacetone phosphate (or glycerone phosphate) from glycolysis is used by the cytosolic enzyme glycerol-3-phosphate dehydrogenase [NAD(+)] to synthesize sn-glycerol 3-phosphate. Second, the mitochondrial outer membrane enzyme glycerol-3-phosphate acyltransferase esterifies an acyl-group to the sn-1 position of sn-glycerol 3-phosphate to form 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid or LPA). Third, the enzyme 1-acyl-sn-glycerol-3-phosphate acyltransferase converts LPA into phosphatidic acid (PA or 1,2-diacyl-sn-glycerol 3-phosphate) by esterifying an acyl-group to the sn-2 position of the glycerol backbone. PA is then transferred to the inner mitochondrial membrane to continue cardiolipin synthesis. Fourth, magnesium-dependent phosphatidate cytidylyltransferase catalyzes the conversion of PA into CDP-diacylglycerol. Fifth, CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase synthesizes phosphatidylglycerophosphate (PGP). Sixth, phosphatidylglycerophosphatase and protein-tyrosine phosphatase dephosphorylates PGP to form phosphatidylglycerol (PG). Last, cardiolipin synthase catalyzes the synthesis of cardiolipin by transferring a phosphatidyl group from a second CDP-diacylglycerol to PG. It requires a divalent metal cation cofactor.

The ketogluconate metabolism starts with the degradation of 2,5-didehydro-D-gluconate either through a NADPH dependent 2,5-diketo-D-gluconate reductase resulting in the release of a NADP and 5-dehydro-D-gluconate or through a NADPH dependent 2,5-diketo-D-gluconate reductase protein complex resulting in the release of a NADP and a 2-keto-L-gulonate. The 2-keto-L-gulonate interacts with a NADPH 2-keto-L-gulonate reductase resulting in a NADP and a L-idonate. The L-idonate interacts with a NADP L-idonate 5-dehydrogenase resulting in the release of hydrogen ion, a NADPH and a 5-dehydro-D-gluconate. The 5-dehydro-D-gluconate interacts with a NADPH driven 5-keto-D-gluconate 5-reductase resulting in the release of a NADP and a D-gluconate. The other way to produce D-gluconate is by having 2,5-Didehydro-D-gluconate interacting with a NADPH and hydrogen ion resulting in the release of a NADP and a 2-keto-D-gluconate which then interact with NADPH a 2-keto-D-gluconate reductase resulting in a NADP and a D-gluconate The D-gluconate is phosphorylated by an ATP driven D-gluconate kinase resulting in a ADP, a hydrogen ion and a D-gluconate 6-phosphate. This compound can either join the Entner-Doudoroff pathway or be metabolized by a NADP dependent 6-phosphogluconate dehydrogenase resulting in a NADPH, a carbon dioxide and a D-ribulose 5-phosphate. The Entner-doudoroff pathway is dehydrated by a phosphogluconate dehydratase resulting in a water molecule and a 2-dehydro-3-deoxy-D-gluconate 6-phosphate. This compound then interacts with a 2-keto-3-deoxygluconate 6-phosphate aldolase resulting in a D-glyceraldehyde 3-phosphate and a pyruvic acid. The d-glyceraldehyde 3-phosphate is incorporated into a glycolysis while the pyruvic acid is decarboxylated into acetyl CoA

PreQ0 or 7-cyano-7-carbaguanine is biosynthesized by degrading GTP. GTP first interacts with water through a GTP cyclohydrolase resulting in the release of a formate, a hydrogen ion and a 7,8-dihydroneopterin 3'-triphosphate. The latter compound then interacts with water through a 6-carboxy-5,6,7,8-tetrahydropterin synthase resulting in a acetaldehyde, triphosphate, 2 hydrogen ion and 6-carboxy-5,6,7,8-tetrahydropterin. The latter compound then reacts spontaneously with a hydrogen ion resulting in the release of a ammonium molecule and a 7-carboxy-7-deazaguanine. This compound then interacts with ATP and ammonium through 7-cyano-7-deazaguanine synthase resulting in the release of water, phosphate, ADP, hydrogen ion and a 7-cyano-7-carbaguanine. The degradation of 7-cyano-7-deazaguanine can lead to produce a preQ1 or a queuine by reacting with 3 hydrogen ions and 2 NADPH through a 7-cyano-7-deazaguanine reductase. PreQ1 then interacts with a guanine 34 in tRNA through a tRNA-guanine transglycosylase resulting in a release of a guanine and a 7-aminomethyl-7-deazaguanosine 34 in tRNA. This nucleic acid then interacts with SAM through a S-adenosylmethionine tRNA ribosyltransferase-isomerase resulting in a release of a hydrogen ion, L-methionine, adenine and an epoxyqueuosine

Menaquinol biosynthesis starts with chorismate being metabolized into isochorismate through a isochorismate synthase. Isochorismate then interacts with 2-oxoglutare and a hydrogen ion through a 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate synthase resulting in the release of a carbon dioxide and a 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate. The latter compound then interacts with (1R,6R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase resulting in the release of a pyruvate and a (1R,6R)-6-hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate. This compound is the dehydrated through a o-succinylbenzoate synthase resulting in the release of a water molecule and a 2-succinylbenzoate. This compound then interacts with a coenzyme A and an ATP through a o-succinylbenzoate CoA ligase resulting in the release of a diphosphate, a AMP and a succinylbenzoyl-CoA. The latter compound interacts with a hydrogen ion through a 1,4-dihydroxy-2-naphthoyl-CoA synthase resulting in the release of a water molecule or a 1,4-dihydroxy-2-naphthoyl-CoA. This compound then interacts with water through a 1,4-dihydroxy-2-naphthoyl-CoA thioesterase resulting in the release of a coenzyme A, a hydrogen ion and a 1,4-dihydroxy-2-naphthoate. The 1,4-dihydroxy-2-naphthoate can interact with either farnesylfarnesylgeranyl-PP or octaprenyl diphosphate and a hydrogen ion through a 1,4-dihydroxy-2-naphthoate octaprenyltransferase resulting in a release of a carbon dioxide, a pyrophosphate and a demethylmenaquinol-8. This compound then interacts with SAM through a bifunctional 2-octaprenyl-6-methoxy-1,4-benzoquinone methylase and S-adenosylmethionine:2-DMK methyltransferase resulting in a hydrogen ion, a s-adenosyl-L-homocysteine and a menaquinol.