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.

Chorismate is an intermediate in tyrosine, phenylalanine and tryptophan synthesis and a precursor for folic acid, ubiquinone, enterochelin and menaquinone. Three enzymes catalyze the first step in chorismate biosynthesis. Synthesis may be reduced by feedback inhibition of tyrosine, phenylalanine and tryptophan to the enzymes. The biosynthesis of chorismate 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. At this point 3-dehydroshikimate can be turned into Shikimic acid through 2 different reactions involving Quinate/shikimate dehydrogenase and shikimate dehydrogenase 2. Shikimic acid is phosphorylated by Shikimate kinase 2 into shikimate 3-phosphate. Shikimate 3- phophate and a phosphoenolpyruvic acid are then joined through a 3-phosphoshikimate 1-carboxyvinyltransferase to produce a 5-enoylpyruvyl-shikimate 3-phosphate while releasing a phosphate. This in turn produces our final product Chorismate through a chorismate synthase.

Palmitate is synthesized by stepwise condensation of C2 units to a growing acyl chain. Each elongation cycle results in the addition of two carbons to the acyl chain, and consists of four separate reactions. The pathway starts with acetyl-CoA interacting with hydrogen carbonate through an ATP driven acetyl-CoA carboxylase resulting in a phosphate, an ADP , a hydrogen ion and a malonyl-CoA. The latter compound interacts with a holo-[acp] through a malonyl-CoA-ACP transacylase resulting in a CoA and a malonyl-[acp]. This compound interacts with hydrogen ion, acetyl-CoA through a KASIII resulting in a CoA, carbon dioxide and an acetoacetyl-[acp]. The latter compound interacts with a hydrogen ion through a NADPH driven 3-oxoacyl-[acyl-carrier-protein] reductase resulting in an NADP and a (R) 3-Hydroxybutanoyl-[acp](1). This compound is then dehydrated by a 3-hydroxyacyl-[acyl-carrier-protein] dehydratase resulting in the release of water and a crotonyl-[acp](2). The crotonyl-[acp] interacts with a hydrogen ion through a NADH enoyl-[acyl-carrier-protein] reductase(NAD) resulting in NAD and a butyryl-[acp](3). The butyryl-[acp] interacts with a hydrogen ion, a malonyl-[acp] through a KASI resulting in a holo-[acp],carbon dioxide and a 3-oxo-hexanoyl-[acp](4). The 3-oxo-hexanoyl-[acp] interacts with a hydrogen ion through a NADPH driven 3-oxoacyl-[acyl-carrier-protein] reductase resulting in an NADP and a (R) 3-Hydroxyhexanoyl-[acp](1). This compound is then dehydrated by a 3-hydroxyacyl-[acyl-carrier-protein] dehydratase resulting in the release of water and a trans hex-2-enoyl-[acp](2). The trans hex-2-enoyl-[acp] interacts with a hydrogen ion through a NADH enoyl-[acyl-carrier-protein] reductase(NAD) resulting in NAD and a hexanoyl-[acp](3). The hexanoyl-[acp] interacts with a hydrogen ion, a malonyl-[acp] through a KASI resulting in a holo-[acp],carbon dioxide and a 3-oxo-octanoyl-[acp](4). The 3-oxo-octanoyl-[acp] interacts with a hydrogen ion through a NADPH driven 3-oxoacyl-[acyl-carrier-protein] reductase resulting in an NADP and a (R) 3-Hydroxyoctanoyl-[acp](1). This compound is then dehydrated by a 3-hydroxyacyl-[acyl-carrier-protein] dehydratase resulting in the release of water and a trans oct-2-enoyl-[acp](2). The trans oct-2-enoyl-[acp] interacts with a hydrogen ion through a NADH enoyl-[acyl-carrier-protein] reductase(NAD) resulting in NAD and a octanoyl-[acp](3). The octanoyl-[acp] interacts with a hydrogen ion, a malonyl-[acp] through a KASI resulting in a holo-[acp],carbon dioxide and a 3-oxo-decanoyl-[acp](4). The 3-oxo-decanoyl-[acp] interacts with a hydrogen ion through a NADPH driven 3-oxoacyl-[acyl-carrier-protein] reductase resulting in an NADP and a (R) 3-Hydroxydecanoyl-[acp](1). This compound is then dehydrated by a 3-hydroxyacyl-[acyl-carrier-protein] dehydratase resulting in the release of water and a trans-delta2-decenoyl-[acp](2). The a trans-delta2-decenoyl-[acp] interacts with a hydrogen ion through a NADH enoyl-[acyl-carrier-protein] reductase(NAD) resulting in NAD and a decanoyl-[acp](3). The decanoyl-[acp] interacts with a malonyl-[acp] through a KASI resulting in a holo-[acp],carbon dioxide and a 3-oxo-dodecanoyl-[acp](4). The 3-oxo-dodecanoyl-[acp ]interacts with a hydrogen ion through a NADPH driven 3-oxoacyl-[acyl-carrier-protein] reductase resulting in an NADP and a (R) 3-Hydroxydodecanoyl-[acp](1). This compound is then dehydrated by a 3-hydroxyacyl-[acyl-carrier-protein] dehydratase resulting in the release of water and a trans dodec-2-enoyl-[acp](2). The trans dodec-2-enoyl-[acp] interacts with a hydrogen ion through a NADH enoyl-[acyl-carrier-protein] reductase(NAD) resulting in NAD and a dodecanoyl-[acp](3). This compound can either react with water spontaneously resulting in a hydrogen ion, a holo-[acp] and a dodecanoic acid or it interacts with a hydrogen ion, a malonyl-[acp] through a KASI resulting in a holo-[acp],carbon dioxide and a 3-oxo-myristoyl-[acp](4). The 3-oxo-myristoyl-[acp] interacts with a hydrogen ion through a NADPH driven 3-oxoacyl-[acyl-carrier-protein] reductase resulting in an NADP and a (3R) 3-Hydroxymyristoyl-[acp](1). This compound is then dehydrated by a 3-hydroxyacyl-[acyl-carrier-protein] dehydratase resulting in the release of water and a trans tetradec-2-enoyl-[acp](2). This compound interacts with a hydrogen ion, through a NADH-driven KASI resulting in a NAD and a myristoyl-[acp]. Myristoyl-[acp] with a hydrogen ion, a malonyl-[acp] through a KASI resulting in a holo-[acp],carbon dioxide and a 3-oxo-palmitoyl-[acp](4). The 3-oxo-palmitoyl-[acp] interacts with a hydrogen ion through a NADPH driven 3-oxoacyl-[acyl-carrier-protein] reductase resulting in an NADP and a (3R) 3-Hydroxypalmitoyl-[acp](1). This compound is then dehydrated by a 3-hydroxyacyl-[acyl-carrier-protein] dehydratase resulting in the release of water and a trans hexadecenoyl-[acp](2). The trans hexadecenoyl-[acp] interacts with a hydrogen ion through a NADH enoyl-[acyl-carrier-protein] reductase(NAD) resulting in NAD and a palmitoyl-[acp](3). Palmitoyl then reacts with water spontaneously resulting in a hydrogen ion, a holo-[acp] and palmitic acid. No integral membrane protein required for long chain fatty acid uptake has been identified in E. coli. The transport of long chain fatty acids across the cytoplasmic membrane is dependent on fatty acyl-CoA synthetase. An energised membrane is necessary for fatty acid transport and it has been suggested that uncharged fatty acids flip across the inner membrane by diffusion.

Tyrosine is one of the amino acid used in protein synthesis. The tyrosine biosynthesis pathways is connected with the chorismate biosynthesis pathway. Chorismate biosynthesis produce the chorismate, which can further be converted to prephenate by T-protein. Combined with cofactor, NAD, prephenate has been further converted to 4-Hydroxyphenylpyruvic acid by T-protein with generated NADH and carbon dioxide. Tyrosine aminotransferase catalyzes 4-Hydroxyphenylpyruvic acid to tyrosine, and also converts glutamic acid to oxoglutaric acid. Tyrosine will be further catalyzed into various molecules such as 2-iminoacetate, p-Cresol, 5'Deoxyadenosine and L-Methionine; or it will be exported from cell via the lysine exporter.

Galactarate is a naturally occurring dicarboxylic acid analog of D-galactose. E. coli can use both diacid sugars galactarate and D-glucarate as the sole source of carbon for growth. The initial step in the degradation of galactarate is its dehydration to 5-dehydro-4-deoxy-D-glucarate(2--) by galactarate dehydratase. Glucaric acid can also be dehydrated by a glucarate dehydratase resulting in water and 5-dehydro-4-deoxy-D-glucarate(2--). The 5-dehydro-4-deoxy-D-glucarate(2--) is then metabolized by a alpha-dehydro-beta-deoxy-D-glucarate aldolase resulting in pyruvic acid and a tartonate semialdehyde. Pyruvic acid interacts with coenzyme A through a NAD driven Pyruvate dehydrogenase complex resulting in a carbon dioxide, an NADH and an acetyl-CoA. The tartronate semialdehyde interacts with a hydrogen ion through a NADPH driven tartronate semialdehyde reductase resulting in a NADP and a glyceric acid. The glyceric acid is phosphorylated by an ATP-driven glycerate kinase 2 resulting in an ADP, a hydrogen ion and a 2-phosphoglyceric acid. The latter compound is dehydrated by an enolase resulting in the release of water and a phosphoenolpyruvic acid. The phosphoenolpyruvic acid interacts with a hydrogen ion through an ADP driven pyruvate kinase resulting in an ATP and a pyruvic acid. The pyruvic acid then interacts with water and an ATP through a phosphoenolpyruvate synthetase resulting in the release of a hydrogen ion, a phosphate, an AMP and a Phosphoenolpyruvic acid.

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.

Glycine biosynthesis is dependent on L-serine. L-serine is enters the cell through transporters (serine / threonine:H+ symporter TdcC, serine/threonine: Na symporter , serine:H+ symporter SdaC) and then proceeds through reversible reaction with a tetrahydrofolic acid through a serine hydroxymethyltransferase enzyme in order to produce glycine, 5,10-methylene tetrahydrofolate and water. 5,10-methylene tetrahydrofolate is a major source of one-carbon units used in other metabolic 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.