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.

Aminopropylcadaverine, a polyamine, is the final product of aminopropylcadaverine biosynthesis pathway. Polyamines are involved in protein synthesis, DNA and RNA related processes, as well as the facilitation of cell stress resistance and membrane integrity; therefore polyamines are essential for cell growth. In this pathway, L-lysine is produced by lysine biosynthesis, then lysine decarboxylase will convert L-lysine into cadaverine. In the final step, spermidine synthase will catalyze cadaverine and decarboxy-SAM to aminopropylcadaverine as well as 5'-Methylthioadenosine.

The process of phenylethylamine metabolism starts with 2-phenylethylamine interacting with an oxygen molecule and a water molecule in the periplasmic space through a phenylethylamine oxidase. This reaction results in the release of a hydrogen peroxide, ammonium and phenylacetaldehyde. Phenylacetaldehyde is introduced into the cytosol and degraded into phenylacetate by reaction with a phenylacetaldehyde dehydrogenase. This reaction involves phenylacetaldehyde interacting with NAD, and a water molecule and then resulting in the release of NADH, and 2 hydrogen ion. Phenylacetate is then degraded. The first step involves phenylacetate interacting with an coenzyme A and an ATP driven phenylacetate-CoA ligase resulting in the release of a AMP, a diphosphate and a phenylacetyl-CoA. This resulting compound the interacts with a hydrogen ion, NADPH, and oxygen molecule through a ring 1,2-phenylacetyl-CoA epoxidase protein complex resulting in the release of a water molecule, an NADP and a 2-(1,2-epoxy-1,2-dihydrophenyl)acetyl-CoA. This compound is then metabolized by a ring 1,2 epoxyphenylacetyl-CoA isomerase resulting in a 2-oxepin-2(3H)-ylideneacetyl-CoA. This compound is then hydrolated through a oxepin-CoA hydrolase resulting in a 3-oxo-5,6-didehydrosuberyl-CoA semialdehyde. This commpound then interacts with a water molecule and NADP driven 3-oxo-5,6-dehydrosuberyl-CoA semialadehyde dehydrogenase resulting in 2 hydrogen ions, a NADPH and a 3-oxo-5,6-didehydrosuberyl-CoA. The resulting compound interacts with a coenzyme A and a 3-oxo-5,6 dehydrosuberyl-CoA thiolase resulting in an acetyl-CoA and a 2,3-didehydroadipyl-CoA. This resulting compound is the hydrated by a 2,3-dehydroadipyl-CoA hydratas resulting in a 3-hydroxyadipyl-CoA whuch is dehydrogenated through an NAD driven 3-hydroxyadipyl-CoA dehydrogenase resulting in a NADH, a hydrogen ion and a 3-oxoadipyl-CoA. The latter compound then interacts with conezyme A through a beta-ketoadipyl-CoA thiolase resulting in an acetyl-CoA and a succinyl-CoA. The succinyl-CoA is then integrated into the TCA cycle.

The process of phenylethylamine metabolism starts with 2-phenylethylamine interacting with an oxygen molecule and a water molecule in the periplasmic space through a phenylethylamine oxidase. This reaction results in the release of a hydrogen peroxide, ammonium and phenylacetaldehyde. Phenylacetaldehyde is introduced into the cytosol and degraded into phenylacetate by reaction with a phenylacetaldehyde dehydrogenase. This reaction involves phenylacetaldehyde interacting with NAD, and a water molecule and then resulting in the release of NADH, and 2 hydrogen ion. Phenylacetate is then degraded. The first step involves phenylacetate interacting with an coenzyme A and an ATP driven phenylacetate-CoA ligase resulting in the release of a AMP, a diphosphate and a phenylacetyl-CoA. This resulting compound the interacts with a hydrogen ion, NADPH, and oxygen molecule through a ring 1,2-phenylacetyl-CoA epoxidase protein complex resulting in the release of a water molecule, an NADP and a 2-(1,2-epoxy-1,2-dihydrophenyl)acetyl-CoA. This compound is then metabolized by a ring 1,2 epoxyphenylacetyl-CoA isomerase resulting in a 2-oxepin-2(3H)-ylideneacetyl-CoA. This compound is then hydrolated through a oxepin-CoA hydrolase resulting in a 3-oxo-5,6-didehydrosuberyl-CoA semialdehyde. This commpound then interacts with a water molecule and NADP driven 3-oxo-5,6-dehydrosuberyl-CoA semialadehyde dehydrogenase resulting in 2 hydrogen ions, a NADPH and a 3-oxo-5,6-didehydrosuberyl-CoA. The resulting compound interacts with a coenzyme A and a 3-oxo-5,6 dehydrosuberyl-CoA thiolase resulting in an acetyl-CoA and a 2,3-didehydroadipyl-CoA. This resulting compound is the hydrated by a 2,3-dehydroadipyl-CoA hydratas resulting in a 3-hydroxyadipyl-CoA whuch is dehydrogenated through an NAD driven 3-hydroxyadipyl-CoA dehydrogenase resulting in a NADH, a hydrogen ion and a 3-oxoadipyl-CoA. The latter compound then interacts with conezyme A through a beta-ketoadipyl-CoA thiolase resulting in an acetyl-CoA and a succinyl-CoA. The succinyl-CoA is then integrated into the TCA cycle.

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.

Uracil is a pyrimidine nucleobase found in RNA, and can be used as a source of nitrogen for E. coli. There are at least three pathways through which uracil is degraded. This one begins with uracil, which originates from purine degradation. The putative monooxygenase enzyme rutA catalyzes the breakdown of uracil into peroxyaminoacrylate, using FMNH2 as a cofactor. Peroxyaminoacrylate is then broken down into both carbamic acid and 3-aminoacrylate following the addition of a water molecule by the putative isochorismatase family protein rutB. Carbamic acid can then spontaneously, with the addition of a hydrogen ion, split into an ammonium ion and a molecule of carbon dioxide. 3-aminoacrylate, on the other hand, is catalyzed by the UPF0076 protein rutC to form 2-aminoacrylic acid. This compound enters into a reaction catalyzed by protein rutD, which adds a water molecule and hydrogen ion and forms malonic semialdehyde with ammonium being a byproduct. Finally, the putative NADH dehydrogenase/NAD(P)H nitroreductase rutE complex converts malonic semialdehyde into hydroxypropionic acid, which is then used to form other necessary chemicals. The ammonium ions produced will be the important source of nitrogen for the bacteria.

This pathway demonstrates the biosynthesis of tetrahydromonapterin in E.coli. However, it is still unclear about biological role of tetrahydromonapterin. GTP cyclohydrolase 1 generates formic acid and 7,8-dihydroneopterin 3'-triphosphate with cofactor GTP and water. 7,8-dihydroneopterin 3'-triphosphate is converted to dihydromonapterin-triphosphate by d-erythro-7,8-dihydroneopterin triphosphate epimerase (folX). Later, dihydromonapterin-triphosphate is hydroxylated to dihydromethysticin, and eventually form tetrahydromonapterin via dihydromonapterin reductase (folM) with cofactor NADPH.

Menaquinol biosynthesis starts with chorismate being metabolized into isochorismate through a isochorismate synthase. Isochorismate then interacts with 2-oxoglutare and a hydrogen ion through a 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate synthase resulting in the release of a carbon dioxide and a 2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexene-1-carboxylate. The latter compound then interacts with (1R,6R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase resulting in the release of a pyruvate and a (1R,6R)-6-hydroxy-2-succinylcyclohexa-2,4-diene-1-carboxylate. This compound is the dehydrated through a o-succinylbenzoate synthase resulting in the release of a water molecule and a 2-succinylbenzoate. This compound then interacts with a coenzyme A and an ATP through a o-succinylbenzoate CoA ligase resulting in the release of a diphosphate, a AMP and a succinylbenzoyl-CoA. The latter compound interacts with a hydrogen ion through a 1,4-dihydroxy-2-naphthoyl-CoA synthase resulting in the release of a water molecule or a 1,4-dihydroxy-2-naphthoyl-CoA. This compound then interacts with water through a 1,4-dihydroxy-2-naphthoyl-CoA thioesterase resulting in the release of a coenzyme A, a hydrogen ion and a 1,4-dihydroxy-2-naphthoate. The 1,4-dihydroxy-2-naphthoate can interact with either farnesylfarnesylgeranyl-PP or octaprenyl diphosphate and a hydrogen ion through a 1,4-dihydroxy-2-naphthoate octaprenyltransferase resulting in a release of a carbon dioxide, a pyrophosphate and a demethylmenaquinol-8. This compound then interacts with SAM through a bifunctional 2-octaprenyl-6-methoxy-1,4-benzoquinone methylase and S-adenosylmethionine:2-DMK methyltransferase resulting in a hydrogen ion, a s-adenosyl-L-homocysteine and a menaquinol.

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