Browsing Pathways

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 biosynthesis of L-tryptophan begins with L-glutamine interacting with a chorismate through a anthranilate synthase which results in a L-glutamic acid, a pyruvic acid, a hydrogen ion and a 2-aminobenzoic acid. The aminobenzoic acid interacts with a phosphoribosyl pyrophosphate through an anthranilate synthase component II resulting in a pyrophosphate and a N-(5-phosphoribosyl)-anthranilate. The latter compound is then metabolized by an indole-3-glycerol phosphate synthase / phosphoribosylanthranilate isomerase resulting in a 1-(o-carboxyphenylamino)-1-deoxyribulose 5'-phosphate. This compound then interacts with a hydrogen ion through a indole-3-glycerol phosphate synthase / phosphoribosylanthranilate isomerase resulting in the release of carbon dioxide, a water molecule and a (1S,2R)-1-C-(indol-3-yl)glycerol 3-phosphate. The latter compound then interacts with a D-glyceraldehyde 3-phosphate and an Indole. The indole interacts with an L-serine through a tryptophan synthase, β subunit dimer resulting in a water molecule and an L-tryptophan. The metabolism of L-tryptophan starts with L-tryptophan being dehydrogenated by a tryptophanase / L-cysteine desulfhydrase resulting in the release of a hydrogen ion, an Indole and a 2-aminoacrylic acid. The latter compound is isomerized into a 2-iminopropanoate. This compound then interacts with a water molecule and a hydrogen ion spontaneously resulting in the release of an Ammonium and a pyruvic acid. The pyruvic acid then interacts with a coenzyme A through a NAD driven pyruvate dehydrogenase complex resulting in the release of a NADH, a carbon dioxide and an Acetyl-CoA

Isoleucine biosynthesis begins with L-threonine from the threonine biosynthesis pathway. L-threonine interacts with threonine dehydratase biosynthetic releasing water, a hydrogen ion and (2Z)-2-aminobut-2-enoate. The latter is isomerized into a 2-iminobutanoate which interacts with water and a hydrogen ion spontaneously, resulting in the release of ammonium and 2-ketobutyric acid. 2-ketobutyric acid reacts with pyruvic acid and hydrogen ions through an acetohydroxybutanoate synthase / acetolactate synthase 2 resulting in carbon dioxide and (S)-2-Aceto-2-hydroxybutanoic acid. (S)-2-Aceto-2-hydroxybutanoic acid is reduced by an NADPH driven acetohydroxy acid isomeroreductase releasing NADP and acetohydroxy acid isomeroreductase. The latter compound is dehydrated by a dihydroxy acid dehydratase resulting in 3-methyl-2-oxovaleric acid. This compound reacts in a reversible reaction with L-glutamic acid through a Branched-chain-amino-acid aminotransferase resulting in oxoglutaric acid and L-isoleucine. L-isoleucine can also be transported into the cytoplasm through two different methods: a branched chain amino acid ABC transporter or a branched chain amino acid transporter BrnQy.

This pathway shows the biosynthesis of methionine, which is an energy-costly process. Lysine biosynthesis produces L-Aspartate-semialdehyde, which later on is catalyzed to L-homoserine by bifunctional aspartokinase (also named homoserine dehydrogenase) 1 and 2. Homoserine is then activated by O-succinylation to form O-succinyl-L-homoserine via homoserine O-succinyltransferase (metA). Combining with L-cysteine, O-succinyl-L-homoserine form L-cystathionine and succinic acid by cystathionine gamma-synthase (metB). Cleavage of L-cystathionine by cystathionine beta-lyase (metC) or Protein MalY(as ) generates two small molecules: homocysteine and 2-aminoprop-2-enoate. Methionine synthase(MetH) or 5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase(MetE) will catalyzehomocysteine to form the final product: methionine. In E.coli, MetH can only function with existence of cobalamin (Vitamin B12), which can be available in the guy; without cobalamin, MetE will not be repressed so that it will catalyze the methionine. Methionine can be transported out of cell (into periplasmic space) by leucine efflux transporter.

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.

This pathway shows the biosynthesis of methionine, which is an energy-costly process. Lysine biosynthesis produces L-Aspartate-semialdehyde, which later on is catalyzed to L-homoserine by bifunctional aspartokinase (also named homoserine dehydrogenase) 1 and 2. Homoserine is then activated by O-succinylation to form O-succinyl-L-homoserine via homoserine O-succinyltransferase (metA). Combining with L-cysteine, O-succinyl-L-homoserine form L-cystathionine and succinic acid by cystathionine gamma-synthase (metB). Cleavage of L-cystathionine by cystathionine beta-lyase (metC) or Protein MalY(as ) generates two small molecules: homocysteine and 2-aminoprop-2-enoate. Methionine synthase(MetH) or 5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase(MetE) will catalyzehomocysteine to form the final product: methionine. In E.coli, MetH can only function with existence of cobalamin (Vitamin B12), which can be available in the guy; without cobalamin, MetE will not be repressed so that it will catalyze the methionine. Methionine can be transported out of cell (into periplasmic space) by leucine efflux transporter.

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.

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.