Browsing Pathways

Asparagine is an amino acid used in protein synthesis, specifically the biosynthesis of glycoproteins. In E.coli, L-asparagine can be synthesized from L-aspartic acid by either utilizing asparagine synthetase B with L-glutamine or ammonia. Both reactions are driven by ATP however the reaction with ammonia utilizes both asparagine synthetase B and aspartate-ammonia ligase.

Asparagine is an amino acid used in protein synthesis, specifically the biosynthesis of glycoproteins. In E.coli, L-asparagine can be synthesized from L-aspartic acid by either utilizing asparagine synthetase B with L-glutamine or ammonia. Both reactions are driven by ATP however the reaction with ammonia utilizes both asparagine synthetase B and aspartate-ammonia ligase.

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.

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.

The biosynthesis of threonine starts with oxalacetic acid interacting with an L-glutamic acid through an aspartate aminotransferase resulting in a oxoglutaric acid and an L-aspartic acid. The latter compound is then phosphorylated by an ATP driven Aspartate kinase resulting in an a release of an ADP and an L-aspartyl-4-phosphate. L-aspartyl-4-phosphate then interacts with a hydrogen ion through an NADPH driven aspartate semialdehyde dehydrogenase resulting in the release of a phosphate, an NADP and a L-aspartate-semialdehyde. The latter compound interacts with a hydrogen ion through a NADPH driven aspartate kinase / homoserine dehydrogenase resulting in the release of an NADP and a L-homoserine. L-homoserine is phosphorylated through an ATP driven homoserine kinase resulting in the release of an ADP, a hydrogen ion and a O-phosphohomoserine. O-phosphohomoserine then interacts with a water molecule and threonine synthase resulting in the release of a phosphate and an L-threonine.

The biosynthesis of L-tryptophan begins with L-glutamine interacting with a chorismate through a anthranilate synthase which results in a L-glutamic acid, a pyruvic acid, a hydrogen ion and a 2-aminobenzoic acid. The aminobenzoic acid interacts with a phosphoribosyl pyrophosphate through an anthranilate synthase component II resulting in a pyrophosphate and a N-(5-phosphoribosyl)-anthranilate. The latter compound is then metabolized by an indole-3-glycerol phosphate synthase / phosphoribosylanthranilate isomerase resulting in a 1-(o-carboxyphenylamino)-1-deoxyribulose 5'-phosphate. This compound then interacts with a hydrogen ion through a indole-3-glycerol phosphate synthase / phosphoribosylanthranilate isomerase resulting in the release of carbon dioxide, a water molecule and a (1S,2R)-1-C-(indol-3-yl)glycerol 3-phosphate. The latter compound then interacts with a D-glyceraldehyde 3-phosphate and an Indole. The indole interacts with an L-serine through a tryptophan synthase, β subunit dimer resulting in a water molecule and an L-tryptophan. The metabolism of L-tryptophan starts with L-tryptophan being dehydrogenated by a tryptophanase / L-cysteine desulfhydrase resulting in the release of a hydrogen ion, an Indole and a 2-aminoacrylic acid. The latter compound is isomerized into a 2-iminopropanoate. This compound then interacts with a water molecule and a hydrogen ion spontaneously resulting in the release of an Ammonium and a pyruvic acid. The pyruvic acid then interacts with a coenzyme A through a NAD driven pyruvate dehydrogenase complex resulting in the release of a NADH, a carbon dioxide and an Acetyl-CoA

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.

The pathway of valine biosynthesis starts with pyruvic acid interacting with a hydrogen ion through a acetolactate synthase / acetohydroxybutanoate synthase or a acetohydroxybutanoate synthase / acetolactate synthase resulting in the release of carbon dioxide and (S)-2-acetolactate. The latter compound then interacts with a hydrogen ion through an NADPH driven acetohydroxy acid isomeroreductase resulting in the release of a NADP and an (R) 2,3-dihydroxy-3-methylvalerate. The latter compound is then dehydrated by a dihydroxy acid dehydratase resulting in the release of water and isovaleric acid. Isovaleric acid interacts with an L-glutamic acid through a Valine Transaminase resulting in a oxoglutaric acid and an L-valine. L-valine is then transported into the periplasmic space through a L-valine 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.

The biosynthesis of L-tryptophan begins with L-glutamine interacting with a chorismate through a anthranilate synthase which results in a L-glutamic acid, a pyruvic acid, a hydrogen ion and a 2-aminobenzoic acid. The aminobenzoic acid interacts with a phosphoribosyl pyrophosphate through an anthranilate synthase component II resulting in a pyrophosphate and a N-(5-phosphoribosyl)-anthranilate. The latter compound is then metabolized by an indole-3-glycerol phosphate synthase / phosphoribosylanthranilate isomerase resulting in a 1-(o-carboxyphenylamino)-1-deoxyribulose 5'-phosphate. This compound then interacts with a hydrogen ion through a indole-3-glycerol phosphate synthase / phosphoribosylanthranilate isomerase resulting in the release of carbon dioxide, a water molecule and a (1S,2R)-1-C-(indol-3-yl)glycerol 3-phosphate. The latter compound then interacts with a D-glyceraldehyde 3-phosphate and an Indole. The indole interacts with an L-serine through a tryptophan synthase, β subunit dimer resulting in a water molecule and an L-tryptophan. The metabolism of L-tryptophan starts with L-tryptophan being dehydrogenated by a tryptophanase / L-cysteine desulfhydrase resulting in the release of a hydrogen ion, an Indole and a 2-aminoacrylic acid. The latter compound is isomerized into a 2-iminopropanoate. This compound then interacts with a water molecule and a hydrogen ion spontaneously resulting in the release of an Ammonium and a pyruvic acid. The pyruvic acid then interacts with a coenzyme A through a NAD driven pyruvate dehydrogenase complex resulting in the release of a NADH, a carbon dioxide and an Acetyl-CoA