Browsing Pathways

The biosynthesis of thiamin begins with a PRPP being degraded by reacting with a water molecule and an L-glutamine through a amidophosphoribosyl transferase resulting in the release of an L-glutamate, a diphosphate and a 5-phospho-beta-d-ribosylamine(PRA). The latter compound, PRA, is further degrade through a phosphoribosylamine glycine ligase by reacting with a glycine and an ATP. This reaction results in the release of a hydrogen ion, an ADP, a phosphate and a N1-(5-phospho-beta-d-ribosyl)glycinamide(GAR). GAR can be metabolized by two different phosphoribosylglycinamide formyltransferase. GAR reacts with a N10-formyl tetrahydrofolate, in this case 10-formyl-tetrahydrofolate mono-L-glutamate, through a phosphoribosylglycinamide formyltransferase 1 resulting in the release of a hydroge ion, a tetrahydrofolate and a N2-formyl-N1-(5-phospho-Beta-D-ribosyl)glycinamide(FGAR). On the other hand, GAR can react with a formate and an ATP molecule through a phosphoribosylglycinamide formyltransferase 2 resulting in a release of a ADP, a phosphate, a hydrogen ion and a FGAR. The FGAR compound gets degraded by interacting with a water molecule, an L-glutamine and an ATP molecule thorugh a phosphoribosylformylglycinamide synthase resulting in the release of a L-glutamate, a phosphate, an ADP molecule, a hydrogen ion and a 2-(formamido)-N1-(5-phopho-Beta-D-ribosyl)acetamidine (FGAM). This compound is further degraded by reacting with an ATP molecule through a phosphoribosylformylglycinamide cyclo-ligase resulting in the release of a phosphate, an ADP, a hydrogen ion and a 5-amino-1-(5-phospho-beta-d-ribosyl)imidazole (AIR). The AIR molecule is degraded by reacting with a S-adenosyl-L-methionine through a HMP-P synthase resulting in the release of 3 hydrogen ions, a carbon monoxide, a formate molecule, L-methionine, 5'-deoxyadenosine and 4- amino-2-methyl-5-phophomethylpyrimidine (HMP-P). This resulting compound is phosphorylated thorugh a ATP driven phosphohydroxymethylpyrimidine kinase resulting in the release of an ADP and 4-amino-2-methyl-5-diphosphomethylpyrimidine (HMP-PP). The resulting compound interacts with a thiazole tautomer and 2 hydrogen ion through a Thiamine phosphate synthase resulting in the release of a pyrophosphate, a carbon dioxide molecule and Thiamin phosphate. This compound is phosphorylated through an ATP driven thiamin monophosphate kinase resulting in a release of an ADP and a thiamin diphosphate.

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.

L-Carnitine can stimulate anaerobic growth of E.coli when exogenous electron acceptors (i.e. nitrate, etc.) are absent. During anaerobic growth, E.coli can reduce L-carnitine to γ-butyrobetaine by CoA-linked intermediates when carbon and nitrogen are present in the system. Therefore, L-carnitine may act as external electron acceptor for anaerobic growth as well as generation of an osmoprotectant for cell.

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.

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.

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

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 pathway can start in various spots. First step in this case starts with NADH interacting with a menaquinone oxidoreductase resulting in the release of a NADH and a hydrogen Ion, at the same time in the inner membrane a menaquinone interacts with 2 electrons and 2 hydrogen ions thus releasing a menaquinol. This allows for 4 hydrogen ions to be transferred from the cytosol to the periplasmic space. The menaquinol then interacts with a trimethylamine N-oxide reductase resulting in the release of 2 hydrogen ion and 2 electrons. At the same time trimethylamine N-oxide and 3 hydrogen ions interact with the enzyme trimethylamine N-oxide reductase resulting in the release of a trimethylamine and a water molecule, this reaction happening in the periplasmic space. The second set of reactions starts with a hydrogen interacting with a menaquinone oxidoreductase resulting in the release of two electrons being released into the inner membrane which then react with with 2 hydrogen ion and a menaquinone to produce a menaquinol. This menaquinol then reacts with a trimethylamine N-oxide reductase following the same steps as mentioned before. The third set of reactions starts with with formate interacting with a formate dehydrogenase-O resulting in a release of carbon dioxide and a hydrogen ion, this releases 2 electrons that interact with a menaquinone and two hydrogen ions. This releases a menaquinol which then reacts with a trimethylamine N-oxide reductase following the same steps as mentioned before

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

Diacetylchitobiose (also known as N,N'-diacetylchitobiose and chitobiose) is a sole source of carbon for E.coli. PTS system mannitol-specific EIICBA component facilitates the imports of diacetylchitobiose as well as the phosphorylation to diacetylchitobiose 6'-phosphate. Later on, diacetylchitobiose 6'-phosphate is hydrolyzed to N-monoacetylchitobiose 6'-phosphate, which also produce acetic acid. N-monoacetylchitobiose 6'-phosphate undergoes further hydrolyzation to form N-Acetyl-D-Glucosamine 6-Phosphate and glucosamine by monoacetylchitobiose-6-phosphate hydrolase.