New pteridine substrates for dihydropteridine reductase and horseradish peroxidase

Abstract

The oxidation of 4,5-diaminopyrimidin-6(1H)-one, 5,6,7,8-tetrahydropteridin-4(3H)-one, its 6-methyl and cis-6,7-dimethyl derivatives, and 6-methyl- and cis-6,7-dimethyl-5,6,7,8-tetrahydropteridins, by horseradish peroxidase/H2O2 is enzymic and follows Michaelis-Menten kinetics, and its K(m) and k(cat.) values were determined. This oxidation of 5,6,7,8-tetrahydropteridins produces quinonoid dihydropterins of established structure, and they are known to be specific substrates for dihydropteridine reductase. By analogy the peroxidase/H2O2 oxidation of the 5,6,7,8-tetrahydropteridin-4(3H)-ones should produce similar quinonoid dihydro species. The quinonoid species derived from 5,6,7,8-tetrahydropteridin-4(3H)-one and its 6-methyl and cis-6,7-dimethyl derivatives are shown to be viable substrates for human brain dihydropteridine reductase, and apparent K(m) and V(max.) values are reported. Show more