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.

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

The process of flavin biosynthesis starts with GTP being metabolized by interacting with 3 molecules of water through a GTP cyclohydrolase resulting in a release of formic acid, a pyrophosphate, two hydrog ions and 2,5-diamino-6-(5-phospho-D-ribosylamino)pyrimidin-4(3H)-one or 2,5-Diamino-6-hydroxy-4-(5-phosphoribosylamino)pyrimidine. Either of these compounds interacts with a water molecule and a hydrogen ion through a fused diaminohydroxyphosphoribosylaminopyrimidine deaminase / 5-amino-6-(5-phosphoribosylamino)uracil reductase resulting in an ammonium and 5-amino-6-(5-phospho-D-ribosylamino)uracil. This compound then interacts with a hydrogen ion through a NADPH dependent fused diaminohydroxyphosphoribosylaminopyrimidine deaminase / 5-amino-6-(5-phosphoribosylamino)uracil reductase resulting in the release of a NADP and a 5-amino-6-(5-phospho-D-ribitylamino)uracil. This compound then interacts with a water molecule through a 5-amino-6-(5-phospho-D-ribitylamino)uracil phosphatase resulting in a release of a phosphate, and a 5-amino-6-(D-ribitylamino)uracil. D-ribulose 5-phosphate interacts with a3,4-dihydroxy-2-butanone 4-phosphate synthase resulting in the release of formic acid, a hydrogen ion and 1-deoxy-L-glycero-tetrulose 4-phosphate. A 5-amino-6-(D-ribitylamino)uracil and 1-deoxy-L-glycero-tetrulose 4-phosphate interact through a 6,7-dimethyl-8-ribityllumazine synthase resulting in the release of 2 water molecules, a phosphate, a hydrogen ion and a 6,7-dimethyl-8-(1-D-ribityl)lumazine. The latter compound then interacts with a hydrogen ion through a riboflavin synthase resulting in the release of a riboflavin and a 5-amino-6-(d-ribitylamino)uracil. The riboflavin is then phosphorylated through an ATP dependent riboflavin kinase resulting in the release of a ADP, a hydrogen ion and a FLAVIN MONONUCLEOTIDE. The flavin mononucleotide interad with a hydrogen ion and an ATP through the riboflavin kinase resulting in the release of a pyrophosphate and Flavin Adenine dinucleotide. This compound is then exported into the periplasm through a FMN/FAD exporter.

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 process of oleic acid B-oxidation starts with a 2-trans,5-cis-tetradecadienoyl-CoA that can be either be processed by an enoyl-CoA hydratase by interacting with a water molecules resulting in a 3-hydroxy-5-cis-tetradecenoyl-CoA, which can be oxidized in the fatty acid beta-oxidation. On the other hand 2-trans,5-cis-tetradecadienoyl-CoA can become a 3-trans,5-cis-tetradecadienoyl-CoA through a isomerase. This results interact with a water molecule through a acyl-CoA thioesterase resulting in a hydrogen ion, a coenzyme A and a 3,5-tetradecadienoate

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

The colonic acid building blocks biosynthesis starts with a Beta-D-Glucose undergoing a transport reaction mediated by a glucose PTS permease. The permease phosphorylates the Beta-D-Glucose, producing a Beta-D-Glucose 6-phosphate. This compound can either change to an Alpha-D-Glucose 6-phosphate spontaneously or into a fructose 6-phosphate through a glucose-6-phosphate isomerase. The latter compound can also be present in E.coli through the interaction of D-fructose and a mannose PTS permease which phosphorylate the D-fructose. Fructose 6-phosphate interacts in a reversible reaction with mannose-6-phosphate isomerase in order to produce a Alpha-D-mannose 6-phosphate. This compound can also be present in E.coli through the interaction of Alpha-D-mannose and a mannose PTS permease which phosphorylates the alpha-D-mannose. Alpha-D-mannose 6-phosphate interacts in a reversible reaction with a phosphomannomutase to produce a alpha-D-mannose 1-phosphate. This compound in turn with a hydrogen ion and gtp undergoes a reaction with a mannose-1-phosphate guanylyltransferase, releasing a pyrophosphate and producing a guanosine diphosphate mannose. Guanosine diphosphate mannose interacts with gdp-mannose 4,6-dehydratase releasing a water, and gdp-4-dehydro-6-deoxy-D-mannose. This compound in turn with hydrogen ion and NADPH interact with GDP-L-fucose synthase releasing NADP and producing a GDP-L-fucose. The Alpha-D-Glucose 6-phosphate interacts in a reversible reaction with phosphoglucomutase-1 to produce a alpha-D-glucose 1-phosphate. This in turn with UTP and hydrogen ion interact with UTP--glucose-1-phosphate uridyleltransferase releasing a pyrophosphate and UDP-glucose. UDP-glucose can either interact with galactose-1-phosphate uridylyltransferase to produce a UDP-galactose or in turn with NAD and water interact with UDP-glucose 6-dehydrogenase releasing a NADH and a hydrogen ion and producing a UDP-glucuronate. GDP-L-fucose, UDP-glucose, UDP-galactose and UDP-glucuronate are sugars that need to be activated in the form of nucleotide sugar prior to their assembly into colanic acid, also known as M antigen. Colanic acid is an extracellular polysaccharide which has been linked to a cluster of 19 genes(wca).

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.