6,7-dimethyltetrahydropterin is a gtp cyclohydrolase i inhibitor.gtp cyclohydrolase i catalyzes the formation of d-erythro-7,8-dihydroneopterin (dihydroneopterin) triphosphate and formate from gtp. dihydroneopterin triphosphate has been identified as a critical intermediate in the biosynthesis of folic acid, pteridines in insects and amphibians, and tetrahydrobiopterin. tetrahydrobiopterin is the obligatory cofactor for tyrosine and tryptophan hydroxylase, which are rate-limiting enzymes for biogenic amine synthesis. tetrahydrobiopterin is the cofactor for phenylalanine hydroxylase as well, which converts lphenylalanine to l-tyrosine.
previous study identified 6,7-dimethyltetrahydropterin as a noncompetitive inhibitor of gtp cyclohydrolase. however, no substrate inhibition of the enzyme was detected 1mm gtp, which is about 8-fold the km value of the enzyme [1]. another study found that phenylalanine hydroxylase could be inhibited by 6,7-dimethyltetrahydropterin, its cofactor. the rate of inactivation, which was irreversible, increased with the concentration of 6,7-dimethyltetrahydropterin. moreover, 6,7-dimethyltetrahydropterin was found to be unstable when the solution was exposed to air but was stabilized by dithiothreitol the aerobic oxidation of which was significantly accelerated by 6,7-dimethyltetrahydropterin [2].
76-112 μm for gtp cyclohydrolase i
[1] shen, r. ,alam, a. and zhang, y. inhibition of gtp cyclohydrolase i by pterins. biochimica et biophysica acta 965, 9-15 (1988).
[2] jakubovic a, woolf li, chan-henry e. the inactivation of phenylalanine hydroxylase by 2-amino-4-hydroxy-6,7-dimethyltetrahydropteridine and the aerobic oxidation of the latter. the effects of catalase, dithiothreitol and reduced nicotinamide-adenine dinucleotide. biochem j. 1971 nov;125(2):563-8.
