Browsing Pathways

The biosynthesis of ubiquinol starts the interaction of 4-hydroxybenzoic acid interacting with an octaprenyl diphosphate. The former compound comes from the chorismate interacting with a chorismate lyase resulting in the release of a pyruvic acid and a 4-hydroxybenzoic acid. On the other hand, the latter compound, octaprenyl diphosphate is the result of a farnesyl pyrophosphate interacting with an isopentenyl pyrophosphate through an octaprenyl diphosphate synthase resulting in the release of a pyrophosphate and an octaprenyl diphosphate. The 4-hydroxybenzoic acid interacts with octaprenyl diphosphate through a 4-hydroxybenzoate octaprenyltransferase resulting in the release of a pyrophosphate and a 3-octaprenyl-4-hydroxybenzoate. The latter compound then interacts with a hydrogen ion through a 3-octaprenyl-4-hydroxybenzoate carboxy-lyase resulting in the release of a carbon dioxide and a 2-octaprenylphenol. The latter compound interacts with an oxygen molecule and a hydrogen ion through a NADPH driven 2-octaprenylphenol hydroxylase resulting in a NADP, a water molecule and a 2-octaprenyl-6-hydroxyphenol. The 2-octaprenyl-6-hydroxyphenol interacts with an S-adenosylmethionine through a bifunctional 3-demethylubiquinone-8 3-O-methyltransferase and 2-octaprenyl-6-hydroxyphenol methylase resulting in the release of a hydrogen ion, an s-adenosylhomocysteine and a 2-methoxy-6-(all-trans-octaprenyl)phenol. The latter compound then interacts with an oxygen molecule and a hydrogen ion through a NADPH driven 2-octaprenyl-6-methoxyphenol hydroxylase resulting in a NADP, a water molecule and a 2-methoxy-6-all trans-octaprenyl-2-methoxy-1,4-benzoquinol. The latter compound interacts with a S-adenosylmethionine through a bifunctional 2-octaprenyl-6-methoxy-1,4-benzoquinone methylase and S-adenosylmethionine:2-DMK methyltransferase resulting in a s-adenosylhomocysteine, a hydrogen ion and a 6-methoxy-3-methyl-2-all-trans-octaprenyl-1,4-benzoquinol. The 6-methoxy-3-methyl-2-all-trans-octaprenyl-1,4-benzoquinol. interacts with a reduced acceptor, an oxygen molecule through a 2-octaprenyl-3-methyl-6-methoxy-1,4-benzoquinone hydroxylase resulting in the release of a water molecule, an oxidized electron acceptor and a 3-demethylubiquinol-8. The latter compound then interacts with a S-adenosylmethionine through a bifunctional 3-demethylubiquinone-8 3-O-methyltransferase and 2-octaprenyl-6-hydroxyphenol methylase resulting in a hydrogen ion, a S-adenosylhomocysteine and a ubiquinol 8.

The biosynthesis of isoprenoids starts with a D-glyceraldehyde 3-phosphate interacting with a hydrogen ion through a 1-deoxyxylulose-5-phosphate synthase resulting in a carbon dioxide and 1-Deoxy-D-xylulose. The latter compound then interacts with a hydrogen ion through a NADPH driven 1-deoxy-D-xylulose 5-phosphate reductoisomerase resulting in a NADP and a 2-C-methyl-D-erythritol 4-phosphate. The latter compound then interacts with a cytidine triphosphate and a hydrogen ion through a 4-diphosphocytidyl-2C-methyl-D-erythritol synthase resulting in a pyrophosphate and a 4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol. The latter compound is then phosphorylated through an ATP driven 4-diphosphocytidyl-2-C-methylerythritol kinase resulting in a release of an ADP, a hydrogen ion and a 2-phospho-4-(cytidine 5'-diphospho)-2-C-methyl-D-erythritol. The latter compound then interacts with a 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase resulting in the release of a 2-C-methyl-D-erythritol-2,4-cyclodiphosphate resulting in the release of a cytidine monophosphate and 2-C-methyl-D-erythritol-2,4-cyclodiphosphate. The latter compound then interacts with a reduced flavodoxin through a 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase resulting in the release of a water molecule, a hydrogen ion, an oxidized flavodoxin and a 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate. The compound 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate can interact with an NADPH,a hydrogen ion through a 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase resulting in a NADP, a water molecule and either a Dimethylallylpyrophosphate or a Isopentenyl pyrophosphate. These two last compounds can be are isomers that can be produced through a isopentenyl diphosphate isomerase. Dimethylallylpyrophosphate interacts with the isopentenyl pyrophosphate through a geranyl diphosphate synthase / farnesyl diphosphate synthase resulting in a pyrophosphate and a geranyl--PP. The latter compound interacts with a Isopentenyl pyrophosphate through a geranyl diphosphate synthase / farnesyl diphosphate synthase resulting in the release of a pyrophosphate and a farnesyl pyrophosphate. The latter compound interacts with isopentenyl pyrophosphate either through a undecaprenyl diphosphate synthase resulting in a release of a pyrophosphate and a di-trans,octa-cis-undecaprenyl diphosphate or through a octaprenyl diphosphate synthase resulting in a pyrophosphate and an octaprenyl diphosphate

The biosynthesis of shikimate 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. A this point 3-dehydroshikimate can be turned into Shikimic acid through 2 different reactions involving an NADPH driven Quinate/shikimate dehydrogenase or a NADPH driven shikimate dehydrogenase 2. Shikimate can also be transported through a shikimate:H+ symporter.

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 metabolism of pyrimidines begins with L-glutamine interacting with water molecule and a hydrogen carbonate through an ATP driven carbamoyl phosphate synthetase resulting in a hydrogen ion, an ADP, a phosphate, an L-glutamic acid and a carbamoyl phosphate. The latter compound interacts with an L-aspartic acid through a aspartate transcarbamylase resulting in a phosphate, a hydrogen ion and a N-carbamoyl-L-aspartate. The latter compound interacts with a hydrogen ion through a dihydroorotase resulting in the release of a water molecule and a 4,5-dihydroorotic acid. This compound interacts with an ubiquinone-1 through a dihydroorotate dehydrogenase, type 2 resulting in a release of an ubiquinol-1 and an orotic acid. The orotic acid then interacts with a phosphoribosyl pyrophosphate through a orotate phosphoribosyltransferase resulting in a pyrophosphate and an orotidylic acid. The latter compound then interacts with a hydrogen ion through an orotidine-5 '-phosphate decarboxylase, resulting in an release of carbon dioxide and an Uridine 5' monophosphate. The Uridine 5' monophosphate process to get phosphorylated by an ATP driven UMP kinase resulting in the release of an ADP and an Uridine 5--diphosphate. Uridine 5-diphosphate can be metabolized in multiple ways in order to produce a Deoxyuridine triphosphate. 1.-Uridine 5-diphosphate interacts with a reduced thioredoxin through a ribonucleoside diphosphate reductase 1 resulting in the release of a water molecule and an oxidized thioredoxin and an dUDP. The dUDP is then phosphorylated by an ATP through a nucleoside diphosphate kinase resulting in the release of an ADP and a DeoxyUridine triphosphate. 2.-Uridine 5-diphosphate interacts with a reduced NrdH glutaredoxin-like protein through a Ribonucleoside-diphosphate reductase 1 resulting in a release of a water molecule, an oxidized NrdH glutaredoxin-like protein and a dUDP. The dUDP is then phosphorylated by an ATP through a nucleoside diphosphate kinase resulting in the release of an ADP and a DeoxyUridine triphosphate. 3.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate. The latter compound interacts with a reduced flavodoxin through ribonucleoside-triphosphate reductase resulting in the release of an oxidized flavodoxin, a water molecule and a Deoxyuridine triphosphate 4.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate The uridine triphosphate interacts with a L-glutamine and a water molecule through an ATP driven CTP synthase resulting in an ADP, a phosphate, a hydrogen ion, an L-glutamic acid and a cytidine triphosphate. The cytidine triphosphate interacts with a reduced flavodoxin through a ribonucleoside-triphosphate reductase resulting in the release of a water molecule, an oxidized flavodoxin and a dCTP. The dCTP interacts with a water molecule and a hydrogen ion through a dCTP deaminase resulting in a release of an ammonium molecule and a Deoxyuridine triphosphate. 5.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate The uridine triphosphate interacts with a L-glutamine and a water molecule through an ATP driven CTP synthase resulting in an ADP, a phosphate, a hydrogen ion, an L-glutamic acid and a cytidine triphosphate. The cytidine triphosphate then interacts spontaneously with a water molecule resulting in the release of a phosphate, a hydrogen ion and a CDP. The CDP then interacts with a reduced NrdH glutaredoxin-like protein through a ribonucleoside-diphosphate reductase 2 resulting in the release of a water molecule, an oxidized NrdH glutaredoxin-like protein and a dCDP. The dCDP is then phosphorylated through an ATP driven nucleoside diphosphate kinase resulting in an ADP and a dCTP. The dCTP interacts with a water molecule and a hydrogen ion through a dCTP deaminase resulting in a release of an ammonium molecule and a Deoxyuridine triphosphate. 6.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate The uridine triphosphate interacts with a L-glutamine and a water molecule through an ATP driven CTP synthase resulting in an ADP, a phosphate, a hydrogen ion, an L-glutamic acid and a cytidine triphosphate. The cytidine triphosphate then interacts spontaneously with a water molecule resulting in the release of a phosphate, a hydrogen ion and a CDP. The CDP interacts with a reduced thioredoxin through a ribonucleoside diphosphate reductase 1 resulting in a release of a water molecule, an oxidized thioredoxin and a dCDP. The dCDP is then phosphorylated through an ATP driven nucleoside diphosphate kinase resulting in an ADP and a dCTP. The dCTP interacts with a water molecule and a hydrogen ion through a dCTP deaminase resulting in a release of an ammonium molecule and a Deoxyuridine triphosphate. The deoxyuridine triphosphate then interacts with a water molecule through a nucleoside triphosphate pyrophosphohydrolase resulting in a release of a hydrogen ion, a phosphate and a dUMP. The dUMP then interacts with a methenyltetrahydrofolate through a thymidylate synthase resulting in a dihydrofolic acid and a 5-thymidylic acid. Then 5-thymidylic acid is then phosphorylated through a nucleoside diphosphate kinase resulting in the release of an ADP and thymidine 5'-triphosphate.

The metabolism of pyrimidines begins with L-glutamine interacting with water molecule and a hydrogen carbonate through an ATP driven carbamoyl phosphate synthetase resulting in a hydrogen ion, an ADP, a phosphate, an L-glutamic acid and a carbamoyl phosphate. The latter compound interacts with an L-aspartic acid through a aspartate transcarbamylase resulting in a phosphate, a hydrogen ion and a N-carbamoyl-L-aspartate. The latter compound interacts with a hydrogen ion through a dihydroorotase resulting in the release of a water molecule and a 4,5-dihydroorotic acid. This compound interacts with an ubiquinone-1 through a dihydroorotate dehydrogenase, type 2 resulting in a release of an ubiquinol-1 and an orotic acid. The orotic acid then interacts with a phosphoribosyl pyrophosphate through a orotate phosphoribosyltransferase resulting in a pyrophosphate and an orotidylic acid. The latter compound then interacts with a hydrogen ion through an orotidine-5 '-phosphate decarboxylase, resulting in an release of carbon dioxide and an Uridine 5' monophosphate. The Uridine 5' monophosphate process to get phosphorylated by an ATP driven UMP kinase resulting in the release of an ADP and an Uridine 5--diphosphate. Uridine 5-diphosphate can be metabolized in multiple ways in order to produce a Deoxyuridine triphosphate. 1.-Uridine 5-diphosphate interacts with a reduced thioredoxin through a ribonucleoside diphosphate reductase 1 resulting in the release of a water molecule and an oxidized thioredoxin and an dUDP. The dUDP is then phosphorylated by an ATP through a nucleoside diphosphate kinase resulting in the release of an ADP and a DeoxyUridine triphosphate. 2.-Uridine 5-diphosphate interacts with a reduced NrdH glutaredoxin-like protein through a Ribonucleoside-diphosphate reductase 1 resulting in a release of a water molecule, an oxidized NrdH glutaredoxin-like protein and a dUDP. The dUDP is then phosphorylated by an ATP through a nucleoside diphosphate kinase resulting in the release of an ADP and a DeoxyUridine triphosphate. 3.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate. The latter compound interacts with a reduced flavodoxin through ribonucleoside-triphosphate reductase resulting in the release of an oxidized flavodoxin, a water molecule and a Deoxyuridine triphosphate 4.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate The uridine triphosphate interacts with a L-glutamine and a water molecule through an ATP driven CTP synthase resulting in an ADP, a phosphate, a hydrogen ion, an L-glutamic acid and a cytidine triphosphate. The cytidine triphosphate interacts with a reduced flavodoxin through a ribonucleoside-triphosphate reductase resulting in the release of a water molecule, an oxidized flavodoxin and a dCTP. The dCTP interacts with a water molecule and a hydrogen ion through a dCTP deaminase resulting in a release of an ammonium molecule and a Deoxyuridine triphosphate. 5.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate The uridine triphosphate interacts with a L-glutamine and a water molecule through an ATP driven CTP synthase resulting in an ADP, a phosphate, a hydrogen ion, an L-glutamic acid and a cytidine triphosphate. The cytidine triphosphate then interacts spontaneously with a water molecule resulting in the release of a phosphate, a hydrogen ion and a CDP. The CDP then interacts with a reduced NrdH glutaredoxin-like protein through a ribonucleoside-diphosphate reductase 2 resulting in the release of a water molecule, an oxidized NrdH glutaredoxin-like protein and a dCDP. The dCDP is then phosphorylated through an ATP driven nucleoside diphosphate kinase resulting in an ADP and a dCTP. The dCTP interacts with a water molecule and a hydrogen ion through a dCTP deaminase resulting in a release of an ammonium molecule and a Deoxyuridine triphosphate. 6.-Uridine 5-diphosphate is phosphorylated by an ATP-driven nucleoside diphosphate kinase resulting in an ADP and an Uridinetriphosphate The uridine triphosphate interacts with a L-glutamine and a water molecule through an ATP driven CTP synthase resulting in an ADP, a phosphate, a hydrogen ion, an L-glutamic acid and a cytidine triphosphate. The cytidine triphosphate then interacts spontaneously with a water molecule resulting in the release of a phosphate, a hydrogen ion and a CDP. The CDP interacts with a reduced thioredoxin through a ribonucleoside diphosphate reductase 1 resulting in a release of a water molecule, an oxidized thioredoxin and a dCDP. The dCDP is then phosphorylated through an ATP driven nucleoside diphosphate kinase resulting in an ADP and a dCTP. The dCTP interacts with a water molecule and a hydrogen ion through a dCTP deaminase resulting in a release of an ammonium molecule and a Deoxyuridine triphosphate. The deoxyuridine triphosphate then interacts with a water molecule through a nucleoside triphosphate pyrophosphohydrolase resulting in a release of a hydrogen ion, a phosphate and a dUMP. The dUMP then interacts with a methenyltetrahydrofolate through a thymidylate synthase resulting in a dihydrofolic acid and a 5-thymidylic acid. Then 5-thymidylic acid is then phosphorylated through a nucleoside diphosphate kinase resulting in the release of an ADP and thymidine 5'-triphosphate.

The colonic acid building blocks biosynthesis starts with a Beta-D-Glucose undergoing a transport reaction mediated by a glucose PTS permease. The permease phosphorylates the Beta-D-Glucose, producing a Beta-D-Glucose 6-phosphate. This compound can either change to an Alpha-D-Glucose 6-phosphate spontaneously or into a fructose 6-phosphate through a glucose-6-phosphate isomerase. The latter compound can also be present in E.coli through the interaction of D-fructose and a mannose PTS permease which phosphorylate the D-fructose. Fructose 6-phosphate interacts in a reversible reaction with mannose-6-phosphate isomerase in order to produce a Alpha-D-mannose 6-phosphate. This compound can also be present in E.coli through the interaction of Alpha-D-mannose and a mannose PTS permease which phosphorylates the alpha-D-mannose. Alpha-D-mannose 6-phosphate interacts in a reversible reaction with a phosphomannomutase to produce a alpha-D-mannose 1-phosphate. This compound in turn with a hydrogen ion and gtp undergoes a reaction with a mannose-1-phosphate guanylyltransferase, releasing a pyrophosphate and producing a guanosine diphosphate mannose. Guanosine diphosphate mannose interacts with gdp-mannose 4,6-dehydratase releasing a water, and gdp-4-dehydro-6-deoxy-D-mannose. This compound in turn with hydrogen ion and NADPH interact with GDP-L-fucose synthase releasing NADP and producing a GDP-L-fucose. The Alpha-D-Glucose 6-phosphate interacts in a reversible reaction with phosphoglucomutase-1 to produce a alpha-D-glucose 1-phosphate. This in turn with UTP and hydrogen ion interact with UTP--glucose-1-phosphate uridyleltransferase releasing a pyrophosphate and UDP-glucose. UDP-glucose can either interact with galactose-1-phosphate uridylyltransferase to produce a UDP-galactose or in turn with NAD and water interact with UDP-glucose 6-dehydrogenase releasing a NADH and a hydrogen ion and producing a UDP-glucuronate. GDP-L-fucose, UDP-glucose, UDP-galactose and UDP-glucuronate are sugars that need to be activated in the form of nucleotide sugar prior to their assembly into colanic acid, also known as M antigen. Colanic acid is an extracellular polysaccharide which has been linked to a cluster of 19 genes(wca).

Phospholipids are membrane components in E. coli. The major phospholipids of E. coli are phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin. All phospholipids contain sn-glycerol-3-phosphate esterified with fatty acids at the sn-1 and sn-2 positions. The reaction starts from a glycerone phosphate (dihydroxyacetone phosphate) produced in glycolysis. The glycerone phosphate is transformed into an sn-glycerol 3-phosphate (glycerol 3 phosphate) by NADPH-driven glycerol-3-phosphate dehydrogenase. sn-Glycerol 3-phosphate is transformed to a 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid). This can be achieved by an sn-glycerol-3-phosphate acyltransferase that interacts either with a long-chain acyl-CoA or with an acyl-[acp]. The 1-acyl-sn-glycerol 3-phosphate is transformed into a 1,2-diacyl-sn-glycerol 3-phosphate (phosphatidic acid) through a 1-acylglycerol-3-phosphate O-acyltransferase. This compound is then converted into a CPD-diacylglycerol through a CTP phosphatidate cytididyltransferase. CPD-diacylglycerol can be transformed either into an L-1-phosphatidylserine or an L-1-phosphatidylglycerol-phosphate through a phosphatidylserine synthase or a phosphatidylglycerophosphate synthase, respectively. The L-1-phosphatidylserine transforms into L-1-phosphatidylethanolamine through a phosphatidylserine decarboxylase. On the other hand, L-1-phosphatidylglycerol-phosphate gets transformed into an L-1-phosphatidyl-glycerol through a phosphatidylglycerophosphatase. These 2 products combine to produce a cardiolipin and an ethanolamine. The L-1 phosphatidyl-glycerol can also interact with cardiolipin synthase resulting in a glycerol and a cardiolipin.

Phospholipids are membrane components in E. coli. The major phospholipids of E. coli are phosphatidylethanolamine, phosphatidylglycerol, and cardiolipin. All phospholipids contain sn-glycerol-3-phosphate esterified with fatty acids at the sn-1 and sn-2 positions. The reaction starts from a glycerone phosphate (dihydroxyacetone phosphate) produced in glycolysis. The glycerone phosphate is transformed into an sn-glycerol 3-phosphate (glycerol 3 phosphate) by NADPH-driven glycerol-3-phosphate dehydrogenase. sn-Glycerol 3-phosphate is transformed to a 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid). This can be achieved by an sn-glycerol-3-phosphate acyltransferase that interacts either with a long-chain acyl-CoA or with an acyl-[acp]. The 1-acyl-sn-glycerol 3-phosphate is transformed into a 1,2-diacyl-sn-glycerol 3-phosphate (phosphatidic acid) through a 1-acylglycerol-3-phosphate O-acyltransferase. This compound is then converted into a CPD-diacylglycerol through a CTP phosphatidate cytididyltransferase. CPD-diacylglycerol can be transformed either into an L-1-phosphatidylserine or an L-1-phosphatidylglycerol-phosphate through a phosphatidylserine synthase or a phosphatidylglycerophosphate synthase, respectively. The L-1-phosphatidylserine transforms into L-1-phosphatidylethanolamine through a phosphatidylserine decarboxylase. On the other hand, L-1-phosphatidylglycerol-phosphate gets transformed into an L-1-phosphatidyl-glycerol through a phosphatidylglycerophosphatase. These 2 products combine to produce a cardiolipin and an ethanolamine. The L-1 phosphatidyl-glycerol can also interact with cardiolipin synthase resulting in a glycerol and a cardiolipin.

Histidine biosynthesis starts with a product of PRPP biosynthesis pathway, phosphoribosyl pyrophosphate which interacts with a hydrogen ion through an ATP phosphoribosyltransferase resulting in an pyrophosphate and a phosphoribosyl-ATP. The phosphoribosyl-ATP interacts with water through a phosphoribosyl-AMP cyclohydrolase / phosphoribosyl-ATP pyrophosphatase resulting in the release of pyrophosphate, hydrogen ion and a phosphoribosyl-AMP. The same enzyme proceeds to interact with phosphoribosyl-AMP and water resulting in a 1-(5'-Phosphoribosyl)-5-amino-4-imidazolecarboxamide. The product is then isomerized by a N-(5'-phospho-L-ribosyl-formimino)-5-amino-1-(5'-phosphoribosyl)-4-imidazolecarboxamide isomerase resulting in a PhosphoribosylformiminoAICAR-phosphate, which reacts with L-glutamine through an imidazole glycerol phosphate synthase resulting in a L-glutamic acid, hydrogen ion, 5-aminoimidazole-4-carboxamide and a D-erythro-imidazole-glycerol-phosphate. D-erythro-imidazole-glycerol-phosphate reacts with a imidazoleglycerol-phosphate dehydratase / histidinol-phosphatase, dehydrating the compound and resulting in a imidazole acetol-phosphate. Next, imidazole acetol-phosphate reacts with L-glutamic acid through a histidinol-phosphate aminotransferase, releasing oxoglutaric acid and L-histidinol-phosphate. The latter compound interacts with water and a imidazoleglycerol-phosphate dehydratase / histidinol-phosphatase resulting in L-histidinol and phosphate. L-histidinol interacts with a NAD-driven histidinol dehydrogenase resulting in a Histidinal. Histidinal in turn reacts with water in a NAD driven histidinal dehydrogenase resulting in L-Histidine. L-Histidine then represses ATP phosphoribosyltransferase, regulation its own biosynthesis.