Browsing Pathways

The creation of L-proline in E. coli starts with L-glutamic acid being phosphorylated through an ATP driven glutamate 5-kinase resulting in a L-glutamic acid 5-phosphate. This compound is then reduced through an NADPH driven gamma glutamyl phosphate reductase resulting in the release of a phosphate, an NADP and a L-glutamic gamma-semialdehyde. L-glutamic gamma-semialdehyde is dehydrated spontaneously, resulting in a release of water,hydrogen ion and 1-Pyrroline-5-carboxylic acid. The latter compound is reduced by an NADPH driven pyrroline-5-carboxylate reductase which is then reduced to L-proline. L-proline works as a repressor of the pyrroline-5-carboxylate reductase enzyme and glutamate 5-kinase. Three genetic loci, proA, proB and proC control the biosynthesis of L-proline in E. coli.The pathway begins with a reaction that is catalyzed by γ-glutamyl kinase, which is encoded by proB. Next, NADPH-dependent reduction of γ-glutamyl phosphate to glutamate-5-semialdehyde, occurs through catalyzation by glutamate-5-semialdehyde dehydrogenase, encoded by proA. Following this, both enzymes join together in a multimeric bi-functional enzyme complex called γ-glutamyl kinase-GP-reductase multienzyme complex. This formation is thought to protect the highly labile glutamyl phosphate from the antagonistic nucleophilic and aqueous environment found in the cell. Finally, NADPH-dependent pyrroline-5-carboxylate reductase encoded by proC catalyzes the reduction of pyrroline 5-carboxylate into L-proline. Proline is metabolized in E. coli by returning to the form of L-glutamate, which is then degraded to α-ketoglutarate,which serves as an intermediary of the TCA cycle. Interestingly enough, L-glutamate, the obligate intermediate of the proline degradation pathway, is not able to serve as an outright source of carbon and energy for E. coli, because the rate at which glutamate transport supplies exogenous glutamate is not adequate. The process by which proline is turned into L-glutamate starts with L-proline interacting with ubiquinone through a bifunctional protein putA resulting in an ubiquinol, a hydrogen ion and a 1-pyrroline-5-carboxylic acid. The latter compound is then hydrated spontaneously resulting in a L-glutamic gamma-semialdehyde. This compound is then processed by interacting with water through an NAD driven bifunctional protein putA resulting in a hydrogen ion, NADH and L-glutamic acid.

This pathway is a compilation of Escherichia coli tRNA charging reactions involving amino acids transported into the cell. The aminoacyl-tRNA synthetase is an enzyme that attaches the appropriate amino acid onto its tRNA by catalyzing the esterification of a specific cognate amino acid or its precursor to one of all its compatible cognate tRNAs to form an aminoacyl-tRNA, which plays an important role in RNA translation. 20 different Aminoacyl-tRNA synthetases can make 20 different types of aa-tRNA for each amino acid according to the genetic code. This process is called "charging" or "loading" the tRNA with amino acid. Ribosome can transfer the amino acid from tRNA to a growing peptide after the tRNA is charged.

Putrescine is an organic chemical produced when amino acids are broken down in organsisms, both living and dead. It can be used as a carbon and nitrogen source in E. coli, and is broken down into gamma-aminobutyric acid (GABA). In this pathway, GABA from putrescine degradation reacts with oxoglutaric acid in a reversible reaction catalyzed by 4-aminobutyrate aminotransferase. This reaction forms succinic acid semialdehyde, as well as L-glutamic acid as a byproduct. Succinic acid semialdehyde is then converted to succinic acid in a reaction catalyzed by succinate-semialdehyde dehydrogenase, using NAD as a cofactor. Succinic acid can then be used by the bacteria in the TCA cycle.

2,3-Dihydroxybenzoate, also known as 2-pyrochatechuic acid or hypogallic acid, is a phenol compound found in bacteria that can be a component of siderophores. These are compounds that strongly bind iron molecules and allow them to be taken up and used by the bacteria in cases of iron scarcity. An example of a siderophore in E. coli is enterobactin, which can be produced from 2,3-dihydroxybenzoate as part of the enterobactin biosynthesis pathway. In this pathway, chorismate, which is the product of the chorismate biosynthesis pathway, is converted to isochorismate in a reaction catalyzed by isochorismate synthase. Following this, a water molecule is added to isochorismate by isochorismatase, which then removes a pyruvic acid molecule as a byproduct, and forms (2S, 3S)-2,3-dihydroxy-2,3-dihydrobenzoate. Finally, 2,3-dihydro-2,3-dihydroxybenzoate dehydrogenase catalyzes the dehydrogenation of (2S, 3S)-2,3-dihydroxy-2,3-dihydrobenzoate into 2-pyrocatechuric acid (2,3-dihydroxybenzoate), using NAD as a cofactor. 2-Pyrocatechuric acid can then be used as a part of the enterobactin biosynthesis pathway, or it can be converted to 2-carboxymuconate by blue copper oxidase cueO.

Lysolipids such as lysophosphatidylethanolamine, lysophosphatidylcholine, lysophosphatidylserine and lysophosphatidylinositol get transported into the cell through a phospholipid ATPase. Once in the cytosol they are incorporated into the ER membrane through a Ale1p transport membrane where phosphatidylcholine is generated.

The biosynthesis of cardiolipin (CL) begins in the endoplasmic reticulum. Glycerone phosphate interacts with an NADPH resulting in the release of NADP and glycerol 3-phosphate. Glycerol 3-phosphate reacts with glycerol-3-phosphate O-acyltransferase resulting in the release of 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid or LysoPA). The resulting compound reacts with an acyl-CoA via lysophosphatidate acyltransferase, resulting in the release of a phosphatidic acid (PA or 1,2-diacyl-sn-glycerol 3-phosphate). Phosphatidic acid is transported to the mitochondrial outer membrane. Once in, it gets transported into the mitochondrial inner membrane. The phosphatidic acid reacts with cytidine triphosphate through a phosphatidate cytidyltransferase resulting in the release of a CDP-diacylglycerol (CDP-DG). The resulting compound reacts with a glycerol 3-phosphate through a CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase resulting in the release of cytidine monophosphate and phosphatidylglycerophosphate (PGP). PGP reacts with phosphatidylglycerophosphatase GEP4 resulting in the release of phosphatidylglycerol (PG). PG reacts with a CDP-DG through a cardiolipin synthase resulting in the release of CL and cytidine monophosphate. Cardiolipin remodelling begins with the removal of an acyl chain to form 1-monolysocardiolipin (1-MLCL) via the lipase Cld1p. This is followed by the enzyme Taz1p transferring an acyl chain from a phospholipid (e.g. phosphatidylcholine) to reform cardiolipin.

A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids. The biosynthesis of triacylglycerol is localized to the endoplasmic reticulum membrane and starts with glycerol 3-phosphate reacting with acyl-CoA through a glycerol-3-phosphate O-acyltransferase resulting in the release of LPA. This, in turn, reacts with an acyl-CoA through a lipase complex resulting in the release of CoA and phosphatidic acid. Phosphatidic acid reacts with water through a phosphatidic acid phosphohydrolase 1 resulting in the release of a phosphate and a diacylglycerol. This reaction can be reversed through a CTP-dependent diacylglycerol kinase. The diacylglycerol reacts in the endoplasmic reticulum with an acyl-CoA through a diacylglycerol O-acyltransferase resulting in the release of coenzyme A and a triacylglycerol. Triacylglycerol metabolism begins with a reaction with water through lipase resulting in the release of a fatty acid, hydrogen ion, and a diacylglycerol. Diacylglycerol then reacts with a lipase 3 resulting in the release of a fatty acid and a monoacylglycerol. Monoacylglycerol reacts with monoglyceride lipase resulting in the release of a fatty acid in glycerol.

Porphyrins are organic compounds. Many porphyrins are involved in oxygen transportation. Porphyrin ring biosynthesis begins in the mitochondria and involves glycine and succinyl-CoA condensation by δ-aminolevulinic acid synthase (ALAS) to produce δ-aminolevulinic acid (ALA), also known as 5-aminolevulinic acid. ALA is then transported to the cytosol where it becomes dimerized by ALA dehydratase (also known as porphobilinogen synthase) to produce porphobilinogen. The pathway continues with the condensation of 4 molecules of porphobilinogen catalyzed by porphobilinogen deaminase (PBG deaminase, also called hydroxymethylbilane synthase or uroporphyrinogen I synthase) to produce hydroxymethylbilane. Hydroxymethylbilane may then be converted to uroporphyrinogen III, a heme intermediate, or it may be non-enzymatically cyclized to uroporphyrinogen I. In the cytosol, uroporphyrinogen I and III substituents become decarboxylated to become coproporphyrinogens. Coproporphyrinogen III is an important intermediate in the synthesis of heme. In the inner mitochondria, coproporphyrinogen III undergoes decarboxylation of 2 propionate residues producing protoporphyrinogen IX. Protoporphyrinogen IX oxidase converts protoporphyrinogen IX to protoporphyrin IX. The final reaction of heme synthesis is ferrochelatase catalyzing the insertion of iron into the ring, producing heme b. Heme is broken down when heme oxygenase opens the heme ring. This oxidation produces linear tetrapyrrole biliverdin, ferric iron (Fe3+), and carbon monoxide (CO). Biliverdin reductase then produces bilirubin.

The pathway starts with the isomerization of Beta-D-galactose into Alpha-D-galactose through a galactose mutarotase. Alpha-D-galactose is then phosphorylated through an ATP dependent galactokinase resulting in the release of ADP, a hydrogen ion and alpha-D-galactose 1-phosphate. The latter compound reacts with UDP glucose which is the result of UTP reacting with alpha-D-glucose through a uridinephosphoglucose pyrophosphorylase. The reaction between alpha-D-galactose 1-phosphate and UDP glucose results in the release of glucose 1-phosphate and UDP-alpha-D-galactose. Glucose 1-phosphate can be further isomerized into glucose 6-phosphate, while UDP-alpha-D-galactose can be reverted into UDP glucose through a UDP-epimerase.

Lipoate is an essential cofactor for key enzymes of oxidative metabolism. Mechanism of lipoate biosynthesis is similar to biotin biosynthesis. Octanoyltransferase facilitates the tranfer of octanoate moiety from octanoate-ACP to particular lysyl residues in lipoate-dependent enzymes. This process regenerates the acyl-carrier in the process, and create an octanylated domains in lipoate-dependent enzymes. Lipoyl synthase combines with S-adenosyl-L-methionine to generate an active lipoylated domain by converting the octanoyl side chain to an active lipoyl. Lipoyl synthase also split S-Adenosyl methionine (AdoMet) into 5'-deoxyadenosyl radical (later becomes 5'-deoxyadenosine by abstracting a hydrogen from a C-H bond) and L-methionine. L-methionine will undergo S-Adenosyl-L-Methionine Biosynthesis.