Enzymes ribotide forming

Biosynthesis is performed in one step by the enzyme L-histidine decarboxylase (HDC, E.C. 4.1.1.22). Histamine metabolism occurs mainly by two pathways. Oxidation is carried out by diamine oxidase (DAO, E.C. 1.4.3.6), leading to imidazole acetic acid (IAA), whereas methyla-tion is effected by histamine N-methyltransferase (HMT, E.C. 2.1.1.8), producing fe/e-methylhistamine (t-MH). IAA can exist as a riboside or ribotide conjugate. t-MH is further metabolized by monoamine oxidase (MAO)-B, producing fe/e-methylimidazole acetic acid (t-MIAA). Note that histamine is a substrate for DAO but not for MAO. Aldehyde intermediates, formed by the oxidation of both histamine and t-MH, are thought to be quickly oxidized to acids under normal circumstances. In the vertebrate CNS, histamine is almost exclusively methylated... 

The biosynthetic pathway is outlined in Figure 1. The thiazole 4 is formed by an oxidative condensation of glycine (1), deoxy-D-xylulose-5-phosphate (DXP, 2), and a sulfide carrier protein with a thiocarboxylate at its carboxy terminus (ThiS-COSH, 3). The pyrimidine phosphate 8 is formed by a deep-seated rearrangement of aminoimidazole ribotide (AIR, 7). It is then pyrophosphorylated and used to alkylate the thiazole to give 10. A final phosphorylation completes the biosynthesis. The entire pathway from glycine, DXP, cysteine, AIR, and ATP has now been reconstituted using purified enzymes. 

The conversion of FGAM to aminoimidazole ribonucleotide (AIR) is catalyzed by the aminoimidazole ribotide synthase, PurM. In this reaction the five-membered ring of the purine base is formed the formyl oxygen is activated by the y-phosphate of the ATP for the nucleophilic attack by N-1 of FGAR, resulting in ring closure [240]. In bacteria, PurM is encoded separately, and in mammals it is part of a trifunctional enzyme, which includes PurD and PurN [241]. 

The coenzymes are formed from dihydrofolic acid by the enzyme dihydrofolate hydrogenase which gives tetrahydrofolic acid (Osborn, Freeman and Huennekens, 1958), and this is then modified by various one-carbon substituents. The coenzyme for the insertion of C-2 into purines, i.e. for the formylation of the ribotide 9 14) to give (9.1 s)y is -formyl-5563738-tetrahydrofolic acid. For the earlier stage of the insertion of C-8, i.e. for the formylation of glycinamide ribotide to form (eventually) (9./ ), the coenzyme is -methenyl-tetrahydrofolic acid (9-/6). The... 

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