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.

Starting from L-threonine, this compound is deaminated through a threonine deaminase resulting in a hydrogen ion, a water molecule and a (2z)-2-aminobut-2-enoate. The latter compound then isomerizes to a 2-iminobutanoate, This compound then reacts spontaneously with hydrogen ion and a water molecule resulting in a ammonium and a 2-Ketobutyric acid. The latter compound interacts with CoA through a pyruvate formate-lyase / 2-ketobutyrate formate-lyase resulting in a formic acid and a propionyl-CoA. Propionyl-CoA can then be processed either into a 2-methylcitric acid or into a propanoyl phosphate. Propionyl-CoA interacts with oxalacetic acid and a water molecule through a 2-methylcitrate synthase resulting in a hydrogen ion, a CoA and a 2-Methylcitric acid.The latter compound is dehydrated through a 2-methylcitrate dehydratase resulting in a water molecule and cis-2-methylaconitate. The latter compound is then dehydrated by a bifunctional aconitate hydratase 2 and 2-methylisocitrate dehydratase resulting in a water molecule and methylisocitric acid. The latter compound is then processed by 2-methylisocitrate lyase resulting in a release of succinic acid and pyruvic acid. Succinic acid can then interact with a propionyl-CoA through a propionyl-CoA:succinate CoA transferase resulting in a propionic acid and a succinyl CoA. Succinyl-CoA is then isomerized through a methylmalonyl-CoA mutase resulting in a methylmalonyl-CoA. This compound is then decarboxylated through a methylmalonyl-CoA decarboxylase resulting in a release of Carbon dioxide and Propionyl-CoA. Propionyl-CoA interacts with a phosphate through a phosphate acetyltransferase / phosphate propionyltransferase resulting in a CoA and a propanoyl phosphate. Propionyl-CoA can react with a phosphate through a phosphate acetyltransferase / phosphate propionyltransferase resulting in a CoA and a propanoyl phosphate. The latter compound is then dephosphorylated through a ADP driven acetate kinase/propionate kinase protein complex resulting in an ATP and Propionic acid. Propionic acid can be processed by a reaction with CoA through a ATP-driven propionyl-CoA synthetase resulting in a pyrophosphate, an AMP and a propionyl-CoA.

The pathway starts with a 3-phosphoglyceric acid interacting with an NAD driven D-3-phosphoglycerate dehydrogenase / α-ketoglutarate reductase resulting in an NADH, a hydrogen ion and a phosphohydroxypyruvic acid. This compound then interacts with an L-glutamic acid through a 3-phosphoserine aminotransferase / phosphohydroxythreonine aminotransferase resulting in a oxoglutaric acid and a DL-D-phosphoserine. The latter compound then interacts with a water molecule through a phosphoserine phosphatase resulting in a phosphate and an L-serine. The L-serine interacts with an acetyl-coa through a serine acetyltransferase resulting in a release of a Coenzyme A and a O-Acetylserine. The O-acetylserine then interacts with a hydrogen sulfide through a O-acetylserine sulfhydrylase A resulting in an acetic acid, a hydrogen ion and an L-cysteine

Leucine biosynthesis involves a five-step conversion process starting with a 3-methyl-2-oxovaleric acid interacting with acetyl-CoA and a water molecule through a 2-isopropylmalate synthase resulting in Coenzyme A, hydrogen Ion and 2-isopropylmalic acid. The latter compound reacts with isopropylmalate isomerase which dehydrates the compound resulting in a Isopropylmaleate. This compound reacts with water through a isopropylmalate isomerase resulting in 3-isopropylmalate. This compound interacts with a NAD-driven D-malate / 3-isopropylmalate dehydrogenase results in 2-isopropyl-3-oxosuccinate. This compound interacts spontaneously with hydrogen resulting in the release of carbon dioxide and ketoleucine. Ketoleucine interacts in a reversible reaction with L-glutamic acid through a branched-chain amino-acid aminotransferase resulting in Oxoglutaric acid and L-leucine. 2-isopropylmalate synthase and terminal transaminase TyrB can both be suppressed by leucine. 2-keto-isovalerate and tyrosine can both inhibit the TyrB, which lead to absence of IlvE activity. Without IlvE activity, 2-ketoisocaproate could not convert to leucine since branched-chain amino-acid aminotransferase (IlvE) is the only enzyme to facilitate the reaction.

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 metabolism of starch and sucrose begins with D-fructose interacting with a D-glucose in a reversible reaction through a maltodextrin glucosidase resulting in a water molecule and a sucrose. D-fructose is phosphorylated through an ATP driven fructokinase resulting in the release of an ADP, a hydrogen ion and a Beta-D-fructofuranose 6-phosphate. This compound can also be introduced into the cytoplasm through either a mannose PTS permease or a hexose-6-phosphate:phosphate antiporter. The Beta-D-fructofuranose 6-phosphate is isomerized through a phosphoglucose isomerase resulting in a Beta-D-glucose 6-phosphate. This compound can also be incorporated by glucose PTS permease or a hexose-6-phosphate:phosphate antiporter. The beta-D-glucose 6 phosphate can also be produced by a D-glucose being phosphorylated by an ATP-driven glucokinase resulting in a ADP, a hydrogen ion and a Beta-D-glucose 6 phosphate. The beta-D-glucose can produce alpha-D-glucose-1-phosphate by two methods: 1.-Beta-D-glucose is isomerized into an alpha-D-Glucose 6-phosphate and then interacts in a reversible reaction through a phosphoglucomutase-1 resulting in a alpha-D-glucose-1-phosphate. 2.-Beta-D-glucose interacts with a putative beta-phosphoglucomutase resulting in a Beta-D-glucose 1-phosphate. Beta-D-glucose 1-phosphate can be incorporated into the cytoplasm through a glucose PTS permease. This compound is then isomerized into a Alpha-D-glucose-1-phosphate The beta-D-glucose can cycle back into a D-fructose by first interacting with D-fructose in a reversible reaction through a Polypeptide: predicted glucosyltransferase resulting in the release of a phosphate and a sucrose. The sucrose then interacts in a reversible reaction with a water molecule through a maltodextrin glucosidase resulting in a D-glucose and a D-fructose. Alpha-D-glucose-1-phosphate can produce glycogen in by two different sets of reactions: 1.-Alpha-D-glucose-1-phosphate interacts with a hydrogen ion and an ATP through a glucose-1-phosphate adenylyltransferase resulting in a pyrophosphate and an ADP-glucose. The ADP-glucose then interacts with an amylose through a glycogen synthase resulting in the release of an ADP and an Amylose. The amylose then interacts with 1,4-α-glucan branching enzyme resulting in glycogen 2.- Alpha-D-glucose-1-phosphate interacts with amylose through a maltodextrin phosphorylase resulting in a phosphate and a glycogen. Alpha-D-glucose-1-phosphate can also interacts with UDP-galactose through a galactose-1-phosphate uridylyltransferase resulting in a galactose 1-phosphate and a Uridine diphosphate glucose. The UDP-glucose then interacts with an alpha-D-glucose 6-phosphate through a trehalose-6-phosphate synthase resulting in a uridine 5'-diphosphate, a hydrogen ion and a Trehalose 6- phosphate. The latter compound can also be incorporated into the cytoplasm through a trehalose PTS permease. Trehalose interacts with a water molecule through a trehalose-6-phosphate phosphatase resulting in the release of a phosphate and an alpha,alpha-trehalose.The alpha,alpha-trehalose can also be obtained from glycogen being metabolized through a glycogen debranching enzyme resulting in a the alpha, alpha-trehalose. This compound ca then be hydrated through a cytoplasmic trehalase resulting in the release of an alpha-D-glucose and a beta-d-glucose. Alpha-D-glucose-1-phosphate can be metabolized to produce dTDP-Beta-L-rhamnose. This happens by Alpha-D-glucose-1-phosphate reacting with a dTTP and a hydrogen ion through a dTDP-glucose pyrophosphorylase resulting in the release of a pyrophosphate and a dTDP-alpha-D-glucose. This coumpound in turn reacts with a dTDP-glucose 4,6-dehydratase resulting in the release of a water molecule and a dTDP-4-dehydro-6-deoxy-alpha-D-glucopyranose. The latter compound reacts with a dTDP-4-dehydrorhamnose 3,5-epimerase resulting in the release of a dTDP-4-dehydro-beta-L-rhamnose. This compound in turn gets metabolized by a NADPH dependent dTDP-4-dehydrorhamnose reductase resulting in a release of a NADP and a dTDP-beta-L-rhamnose Glycogen is then metabolized by reacting with a phosphate through a glycogen phosphorylase resulting in a alpha-D-glucose-1-phosphate and a dextrin. The dextrin is then hydrated through a glycogen phosphorylase-limit dextrin α-1,6-glucohydrolase resulting in the release of a debranched limit dextrin and a maltotetraose. This compound can also be incorporated into the cytoplasm through a maltose ABC transporter. The maltotetraose interacts with a phosphate through a maltodextrin phosphorylase releasing a alpha-D-glucose-1-phosphate and a maltotriose. The maltotriose can also be incorporated through a maltose ABC transporter. The maltotriose can then interact with water through a maltodextrin glucosidase resulting in a D-glucose and a D-maltose. D-maltose can also be incorporated through a maltose ABC transporter The D-maltose can then interact with a maltotriose through a amylomaltase resulting in a maltotetraose and a D-glucose. The D-glucose is then phosphorylated through an ATP driven glucokinase resulting in a hydrogen ion, an ADP and a Beta-D-glucose 6-phosphate

Phospholipids are membrane components in E. coli. The major phospholipids of E. coli are phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin. All phospholipids contain sn-glycerol-3-phosphate esterified with fatty acids at the sn-1 and sn-2 positions. The reaction starts from a glycerone phosphate (dihydroxyacetone phosphate) produced in glycolysis. The glycerone phosphate is transformed into an sn-glycerol 3-phosphate (glycerol 3 phosphate) by NADPH-driven glycerol-3-phosphate dehydrogenase. sn-Glycerol 3-phosphate is transformed to a 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid). This can be achieved by an sn-glycerol-3-phosphate acyltransferase that interacts either with a long-chain acyl-CoA or with an acyl-[acp]. The 1-acyl-sn-glycerol 3-phosphate is transformed into a 1,2-diacyl-sn-glycerol 3-phosphate (phosphatidic acid) through a 1-acylglycerol-3-phosphate O-acyltransferase. This compound is then converted into a CPD-diacylglycerol through a CTP phosphatidate cytididyltransferase. CPD-diacylglycerol can be transformed either into an L-1-phosphatidylserine or an L-1-phosphatidylglycerol-phosphate through a phosphatidylserine synthase or a phosphatidylglycerophosphate synthase, respectively. The L-1-phosphatidylserine transforms into L-1-phosphatidylethanolamine through a phosphatidylserine decarboxylase. On the other hand, L-1-phosphatidylglycerol-phosphate gets transformed into an L-1-phosphatidyl-glycerol through a phosphatidylglycerophosphatase. These 2 products combine to produce a cardiolipin and an ethanolamine. The L-1 phosphatidyl-glycerol can also interact with cardiolipin synthase resulting in a glycerol and a cardiolipin.

The biosynthesis of isoprenoids starts with a D-glyceraldehyde 3-phosphate interacting with a hydrogen ion through a 1-deoxyxylulose-5-phosphate synthase resulting in a carbon dioxide and 1-Deoxy-D-xylulose. The latter compound then interacts with a hydrogen ion through a NADPH driven 1-deoxy-D-xylulose 5-phosphate reductoisomerase resulting in a NADP and a 2-C-methyl-D-erythritol 4-phosphate. The latter compound then interacts with a cytidine triphosphate and a hydrogen ion through a 4-diphosphocytidyl-2C-methyl-D-erythritol synthase resulting in a pyrophosphate and a 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol. The latter compound is then phosphorylated through an ATP driven 4-diphosphocytidyl-2-C-methylerythritol kinase resulting in a release of an ADP, a hydrogen ion and a 2-phospho-4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol. The latter compound then interacts with a 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase resulting in the release of a 2-C-methyl-D-erythritol-2,4-cyclodiphosphate resulting in the release of a cytidine monophosphate and 2-C-methyl-D-erythritol-2,4-cyclodiphosphate. The latter compound then interacts with a reduced flavodoxin through a 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase resulting in the release of a water molecule, a hydrogen ion, an oxidized flavodoxin and a 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate. The compound 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate can interact with an NADPH,a hydrogen ion through a 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase resulting in a NADP, a water molecule and either a Dimethylallylpyrophosphate or a Isopentenyl pyrophosphate. These two last compounds can be are isomers that can be produced through a isopentenyl diphosphate isomerase. Dimethylallylpyrophosphate interacts with the isopentenyl pyrophosphate through a geranyl diphosphate synthase / farnesyl diphosphate synthase resulting in a pyrophosphate and a geranyl--PP. The latter compound interacts with a Isopentenyl pyrophosphate through a geranyl diphosphate synthase / farnesyl diphosphate synthase resulting in the release of a pyrophosphate and a farnesyl pyrophosphate. The latter compound interacts with isopentenyl pyrophosphate either through a undecaprenyl diphosphate synthase resulting in a release of a pyrophosphate and a di-trans,octa-cis-undecaprenyl diphosphate or through a octaprenyl diphosphate synthase resulting in a pyrophosphate and an octaprenyl diphosphate

Starting from L-threonine, this compound is deaminated through a threonine deaminase resulting in a hydrogen ion, a water molecule and a (2z)-2-aminobut-2-enoate. The latter compound then isomerizes to a 2-iminobutanoate, This compound then reacts spontaneously with hydrogen ion and a water molecule resulting in a ammonium and a 2-Ketobutyric acid. The latter compound interacts with CoA through a pyruvate formate-lyase / 2-ketobutyrate formate-lyase resulting in a formic acid and a propionyl-CoA. Propionyl-CoA can then be processed either into a 2-methylcitric acid or into a propanoyl phosphate. Propionyl-CoA interacts with oxalacetic acid and a water molecule through a 2-methylcitrate synthase resulting in a hydrogen ion, a CoA and a 2-Methylcitric acid.The latter compound is dehydrated through a 2-methylcitrate dehydratase resulting in a water molecule and cis-2-methylaconitate. The latter compound is then dehydrated by a bifunctional aconitate hydratase 2 and 2-methylisocitrate dehydratase resulting in a water molecule and methylisocitric acid. The latter compound is then processed by 2-methylisocitrate lyase resulting in a release of succinic acid and pyruvic acid. Succinic acid can then interact with a propionyl-CoA through a propionyl-CoA:succinate CoA transferase resulting in a propionic acid and a succinyl CoA. Succinyl-CoA is then isomerized through a methylmalonyl-CoA mutase resulting in a methylmalonyl-CoA. This compound is then decarboxylated through a methylmalonyl-CoA decarboxylase resulting in a release of Carbon dioxide and Propionyl-CoA. Propionyl-CoA interacts with a phosphate through a phosphate acetyltransferase / phosphate propionyltransferase resulting in a CoA and a propanoyl phosphate. Propionyl-CoA can react with a phosphate through a phosphate acetyltransferase / phosphate propionyltransferase resulting in a CoA and a propanoyl phosphate. The latter compound is then dephosphorylated through a ADP driven acetate kinase/propionate kinase protein complex resulting in an ATP and Propionic acid. Propionic acid can be processed by a reaction with CoA through a ATP-driven propionyl-CoA synthetase resulting in a pyrophosphate, an AMP and a propionyl-CoA.

Cobinamide is incorporated from the extracellular space through a transport system into the cytosol. Once inside the cytosol, cobinamide interacts with ATP through a cobinamide adenosyl transferase resulting in the release of a triphosphate and an adenosylcobinamide. The latter compound is then phosphorylated through an ATP-dependent cobinamide kinase resulting in the release of ADP, a hydrogen ion and adenosyl-cobinamide phosphate. This last compound then interacts with GTP and a hydrogen ion through a cobinamide-P guanylyltransferase resulting in the release of a pyrophosphate and an adenosylcobinamide-GDP. A dimethylbenzimidazole interacts with a nicotinate D-ribonucleotide through a nicotinate-nucleotide dimethylbenzumidazole phosphoribosyltransferase resulting in the release of a nicotinate, a hydrogen ion and an alpha-ribazole 5' phosphate. The adenosylcobinamide-GDP and the alpha-ribazole 5' phosphate interact together through a cobalamin 5' phosphate synthase resulting in the release of a hydrogen ion, a GMP and Adenosylcobalamin 5'-phosphate. The latter compound then interacts with a water molecule through an adenosylcbalamin 5' phosphate phosphatase resulting in the release of a phosphate and a coenzyme B12. Likewise a cobalamin molecule can interact with ATP through a cobalamin adenosyltransferase resulting in the release of a triphosphate and a coenzyme B12