Browsing Pathways

The selenium metabolism begins with the introduction of selenate and selenite to the cytosol through a sulphate permease system. Once in the cell, selenate can be reduced to selenite through nitrate reductases A and Z. Selenite then interacts with glutathione and 2 hydrogen ions resulting in the release of 2 water molecules, a hydroxide molecule, a glutathione disulfide and a selenodiglutathione. The latter compound then reacts with NADPH+H resulting in the release of a NADP, a glutathione and a glutathioselenol. Glutathiolselenol can then be oxidize resulting in a a glutathiolselenol ion which can then interact with a water molecule resulting in a release of glutathion and selenium Glutathiolselenol can also react with NADPH and hydrogen ion resulting in a release of glutathione, NADP, a hydroxide molecule and a hydrogen selenide. This compound can react in a reversible reaction by being oxidized resulting in a hydrogen selenide ion . This compound can then be phosphorylated by interacting with an ATP and releasing a AMP, a phosphate and a selenophosphate.

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.

Curcumin is metabolized by being reduced through a NADPH dependent curcumin reductase resulting in a dihydrocurcumin. This compound is then reduced again through a NADPH-dependent dihydrocurcumin reductase resulting in a tetrahydrocurcumin. It is not know yet how this compound enters E.coli

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 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.

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 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