Browsing Pathways

D-allose can be used as source of carbon for E.coli. D-allose is imported into E.coli by D-allose ABC transporter without phosphorylation. Allose-6-phosphate isomerase and allulose-6-phosphate 3-epimerase catalyze the remaining reactions resulting in D-allulose 6 phosphate and Beta-D-fructofuranose 6-phosphate respectively. Once Beta D fructofuranose 6-phosphate is synthesized, it can be used in the glycolysis and pyruvatedehydrogenase pathway.

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.

In E. coli, L-fucose and L-rhamnose are metabolized through parallel pathways. The pathways converge after their corresponding aldolase reactions yielding the same products: lactaldehye. Proton symporter can facilitate the import of alpha-L-rhamnopyranose, methylpentose and beta-L-rhamnopyranose into cell for further metabolism, which allow E.coli to grow with carbon and energy. For alpha-L-rhamnopyranose, it is isomerized by a l-rhamnose mutarotase resulting in a beta-L-rhamnopyranose which is then isomerized into a keto-L-rhamnulose by a l-rhamnose isomerase. The keto-L-rhamnulose spontaneously changes into a L-rhamnulofuranose which is phosphorylated by a rhamnulokinase resulting in a L-rhamnulose 1-phosphate. This compound reacts with a rhamnulose-1-phosphate aldolase resulting in a dihydroxyacetone phosphate and a lactaldehyde. For beta-L-rhamnopyranose, it is isomerized by a L-fucose mutarotase resulting in a alpha-L-fucopyranose. This compound is then isomerized by an L-fucose isomerase resulting in a L-fuculose which in turn gets phosphorylated into an L-fuculose 1-phosphate through an L-fuculokinase. The compound L-fuculose 1-phosphate reacts with an L-fuculose phosphate aldolase through a dihydroxyacetone phosphate and a lactaldehyde. Two pathways can both be used for degrading L-lactaldehyde, which the aerobic pathway facilitates the conversion from L-lactic acid to pyruvic acid via L-lactate dehydrogenase, and the anaerobic pathway facilitates conversion from lactaldehyde to propane-1,2-diol via lactaldehyde reductase. Under aerobic conditions, L-lactaldehyde is oxidized in two steps to pyruvate, thereby channeling all the carbons from fucose or rhamnose into central metabolic pathways. Under anaerobic conditions, L-lactaldehyde is reduced to L-1,2-propanediol, which is secreted into the environment.

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.

Escherichia coli can utilize D-mannose for its sole carbon and energy source. Alpha-D-mannose is introduced into the cytoplasm through a mannose PTS permease. A phosphotransferase system (PTS) takes up mannose producing D-mannose-6-phosphate which is then converted to D-fructose-6-phosphate via an isomerase. D-fructose-6-phosphate is an intermediate of glycolysis and can enter the pathways of metabolism. The first two enzymes in the pathway catalyze isomerizations that interconvert phosphorylated aldohexoses (β-D-glucose-6-phosphate, D-mannose-6-phosphate) and phosphorylated ketohexoses (D-fructose-6-phosphate). The reaction catalyzed by mannose-6-phosphate isomerase that produces D-mannose-6-phosphate is the first committed step in the biosynthesis of the activated mannose donor GDP-α-D-mannose. D-mannose-6-phosphate is then converted to GDP-D-mannose by the interaction of phosphomannomutase and mannose-1-phosphate guanylyltransferase. GDP-D-mannose produces GDP-L-fucose beginning with the dehydration to GDP-4-dehydro-6-deoxy-D-mannose. GDP-fucose is synthesized by a two step epimerase and reductase of GDP-4-dehydro-6-deoxy-D-mannose. L-fucose then enters the colanic acid building blocks biosynthesis pathway.

Gluconeogenesis from L-malic acid starts from the introduction of L-malic acid into cytoplasm either through a C4 dicarboxylate / orotate:H+ symporter or a dicarboxylate transporter (succinic acid antiporter). L-malic acid is then metabolized through 3 possible ways: NAD driven malate dehydrogenase resulting in oxalacetic acid, NADP driven malate dehydrogenase B resulting pyruvic acid or malate dehydrogenase, NAD-requiring resulting in pyruvic acid. Oxalacetic acid is processed by phosphoenolpyruvate carboxykinase (ATP driven) while pyruvic acid is processed by phosphoenolpyruvate synthetase resulting in phosphoenolpyruvic acid. This compound is dehydrated by enolase resulting in an 2-phosphoglyceric acid which is then isomerized by 2,3-bisphosphoglycerate-independent phosphoglycerate mutase resulting in a 3-phosphoglyceric acid which is phosphorylated by an ATP driven phosphoglycerate kinase resulting in a glyceric acid 1,3-biphosphate. This compound undergoes an NADH driven glyceraldehyde 3-phosphate dehydrogenase reaction resulting in a D-Glyceraldehyde 3-phosphate which is first isomerized into dihydroxyacetone phosphate through an triosephosphate isomerase. D-glyceraldehyde 3-phosphate and Dihydroxyacetone phosphate react through a fructose biphosphate aldolase protein complex resulting in a fructose 1,6-biphosphate. Fructose 1,6-biphosphateis is metabolized by a fructose-1,6-bisphosphatase resulting in a Beta-D-fructofuranose 6-phosphate which is then isomerized into a Beta-D-glucose 6-phosphate through a glucose-6-phosphate isomerase.

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.

Leucine biosynthesis involves a five-step conversion process starting with the valine precursor 2-keto-isovalerate interacting with acetyl-CoA and water through a 2-isopropylmalate synthase resulting in Coenzyme A, hydrogen Ion and 2-isopropylmalic acid. The latter compound reacts with isopropylmalate isomerase which dehydrates the compound resulting in a Isopropylmaleate. This compound reacts with water through a isopropylmalate isomerase resulting in 3-isopropylmalate. This compound interacts with a NAD-driven D-malate / 3-isopropylmalate dehydrogenase results in 2-isopropyl-3-oxosuccinate. This compound interacts spontaneously with hydrogen resulting in the release of carbon dioxide and ketoleucine. Ketoleucine interacts in a reversible reaction with L-glutamic acid through a branched-chain amino-acid aminotransferase resulting in Oxoglutaric acid and L-leucine. L-leucine can then be exported outside the cytoplasm through a transporter: L-amino acid efflux transporter. In the final step, ketoleucine can be catalyzed to form L-leucine by branched-chain amino-acid aminotransferase (IlvE) and tyrosine aminotransferase (TryB). L-Glutamic acid can also be transformed into oxoglutaric acid by these two enzymes. Tyrosine aminotransferase can be suppressed by lecuine, and inhibited by 2-keto-isovarlerate and its end product, tyrosine. 2-ketoisocaproate can not be introduced if 2-keto-isovarlerate inhibit TyrB and IlvE is absent.

This pathway shows the biosynthesis of methionine, which is an energy-costly process. Lysine biosynthesis produces L-Aspartate-semialdehyde, which later on is catalyzed to L-homoserine by bifunctional aspartokinase (also named homoserine dehydrogenase) 1 and 2. Homoserine is then activated by O-succinylation to form O-succinyl-L-homoserine via homoserine O-succinyltransferase (metA). Combining with L-cysteine, O-succinyl-L-homoserine form L-cystathionine and succinic acid by cystathionine gamma-synthase (metB). Cleavage of L-cystathionine by cystathionine beta-lyase (metC) or Protein MalY(as ) generates two small molecules: homocysteine and 2-aminoprop-2-enoate. Methionine synthase(MetH) or 5-methyltetrahydropteroyltriglutamate--homocysteine methyltransferase(MetE) will catalyzehomocysteine to form the final product: methionine. In E.coli, MetH can only function with existence of cobalamin (Vitamin B12), which can be available in the guy; without cobalamin, MetE will not be repressed so that it will catalyze the methionine. Methionine can be transported out of cell (into periplasmic space) by leucine efflux transporter.

Chorismate is an intermediate in tyrosine, phenylalanine and tryptophan synthesis and a precursor for folic acid, ubiquinone, enterochelin and menaquinone. Three enzymes catalyze the first step in chorismate biosynthesis. Synthesis may be reduced by feedback inhibition of tyrosine, phenylalanine and tryptophan to the enzymes. The biosynthesis of chorismate 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. At this point 3-dehydroshikimate can be turned into Shikimic acid through 2 different reactions involving Quinate/shikimate dehydrogenase and shikimate dehydrogenase 2. Shikimic acid is phosphorylated by Shikimate kinase 2 into shikimate 3-phosphate. Shikimate 3- phophate and a phosphoenolpyruvic acid are then joined through a 3-phosphoshikimate 1-carboxyvinyltransferase to produce a 5-enoylpyruvyl-shikimate 3-phosphate while releasing a phosphate. This in turn produces our final product Chorismate through a chorismate synthase.