Browsing Pathways

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.

The biosynthesis of shikimate starts with D-Erythrose-4-phosphate getting transformed into 3-deoxy-D-arabino-heptulosonate-7-phosphate through a phospho-2-dehydro-3-deoxyheptonate aldolase. This is followed by a 3-dehydroquinate synthase converting the 3-deoxy-D-arabino-heptulosonate-7-phosphate into a 3-dehydroquinate which in turn is conveted to 3-dehydroshikimate through a 3-dehydroquinate dehydratase. A this point 3-dehydroshikimate can be turned into Shikimic acid through 2 different reactions involving an NADPH driven Quinate/shikimate dehydrogenase or a NADPH driven shikimate dehydrogenase 2. Shikimate can also be transported through a shikimate:H+ symporter.

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.

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

The biosynthesis of threonine starts with L-aspartic acid being phosphorylated by an ATP driven Aspartate kinase resulting in an a release of an ADP and an L-aspartyl-4-phosphate. This compound interacts with a hydrogen ion through an NADPH driven aspartate semialdehyde dehydrogenase resulting in the release of a phosphate, an NADP and a L-aspartate-semialdehyde.The latter compound interacts with a hydrogen ion through a NADPH driven aspartate kinase / homoserine dehydrogenase resulting in the release of an NADP and a L-homoserine. L-homoserine is phosphorylated through an ATP driven homoserine kinase resulting in the release of an ADP, a hydrogen ion and a O-phosphohomoserine. The latter compound then interacts with a water molecule threonine synthase resulting in the release of a phosphate and an L-threonine.

GTP, produced in the nucleotide de novo biosyntheis pathway, interacts with a water molecule through a GTP cyclohydrolase resulting in a formate, hydrogen ion and a 7,8-dihydroneopterin 3'-triphosphate. The latter compound interacts with a water molecule through a dihydroneopterin triphosphate pyrophosphohydrolase resulting in the release of a pyrophosphate, a hydrogen ion and a 7,8-dihydroneopterin 3'-phosphate. The latter compound interacts with water spontaneously resulting in the release of a phosphate and a 7,8 dihydroneopterin. The latter compound interacts with a dihydroneopterin aldolase resulting in the release of a glycolaldehyde and a 6-hydroxymethyl-7,8-dihydropterin. This compound then is then diphosphorylated by reacting with a ATP driven 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase resulting in the release of a hydrogen ion, an AMP and 6-hydroxymethyl-7,8-dihydropterin diphosphate. GTP interacts with a cyclic pyranopterin monophosphate synthase resulting in the release of a diphosphate and a cyclic pyranopterin phosphate. The latter compound interacts with a thiocarboxylated small subunit of molybdopterin synthase (a protein) and a water molecule through a molybdopterin synthase resulting in the release of 4 hydrogen ions, 2 small subunits of molybdopterin synthase and a molybdopterin. The molybdopterin interacts with an ATP and a hydrogen ion through a molybdopterin adenylyltransferase resulting in the release of a diphosphate and a molybdopterin adenine dinucleotide. The latter compound is then metabolized by a hydrogen ion and a molybdate through a molybdopterin molybdenumtransferase resulting in the release of an AMP, a water molecule and a molybdopterin cofactor. The molybdopterin cofactor can procede to the guanylyl molybdenum cofactor biosynthesis pathway or it can be metabolized into a cytidylyl molybdenum cofactor by interacting with a CTP and a hydrogen ion through a molybdenym cofactor cytidylyltransferase resulting in the release of a pyrophosphate and a cytidyllyl molybdenum 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.