GTP cyclohydrolase II catalyzes the first committed reaction in the biosynthesis of the vitamin riboflavin. The recombinant enzyme from Escherichia coli is shown to produce 2,5-diamino-6-beta-ribosylamino-4(3H)-pyrimidinone 5'-phosphate and GMP at an approximate molar ratio of 10:1. The main product is subject to spontaneous isomerization affording the alpha-anomer. (18)O from solvent water is incorporated by the enzyme into the phosphate group of the 5-aminopyrimidine derivative as well as GMP. These data are consistent with the transient formation of a covalent phosphoguanosyl derivative of the enzyme. Subsequent ring opening of the covalently bound nucleotide followed by hydrolysis of the phosphodiester bond could then afford the pyrimidine type product. The hydrolysis of the phosphodiester bond without prior ring opening could afford GMP. The enzyme reaction is cooperative with a Hill coefficient of 1.3. Inhibition by pyrophosphate is competitive. Inhibition by orthophosphate is partially uncompetitive at low concentration and competitive at concentrations above 6 mm.
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