标题：AN EXTREME DIMINUTION IN THE STRONG AFFINITY OF 2-AMINO-4-HYDROXY-6-FORMYLPTERIDINE FOR XANTHINE OXIDASE BY REDUCTION OF A 7, 8-DOUBLE BOND OR A FORMYL GROUP AT POSITION 6 OF ITS PYRAZINE RING
期刊名称：Journal of Nutritional Science and Vitaminology
印刷版ISSN：0301-4800
电子版ISSN：1881-7742
出版年度：1974
卷号：20
期号：4
页码：317-331
DOI：10.3177/jnsv.20.317
出版社：Center for Academic Publications Japan
摘要：The initial velocity of xanthine oxidase reaction catalyzed by milk xanthine oxidase is determined over the range of substrate concentrations from 1 to 0.005mM by following the consumption of molecular oxygen by a polarographic method using a Clark oxygen electrode. The Michaelis constant determined is 1.3×10-5M. The activity is blocked by the substrate levels higher than 40μM. The constant for the substrate inhibition is calculated to be 1.3×10-3M. The strong inhibition of the enzyme by 2-amino-4-hydroxy-6-formylpteridine develops with time: the constant for dissociation of the enzyme-inhibitor complex, K i, is determined to be 8.0×10-8M when the enzyme is not treated with the inhibitor prior to the start of the reaction by addition of the substrate, but 7.0×10-9M when pretreatment for 10min is made. This potency, however, is markedly decreased by the reduction of a 7, 8-double bond or a formyl group at position 6 of the pyrazine ring of the antagonist. 2-Amino-4-hydroxy-6-formyl-7, 8-dihydropteridine and 2-amino-4-hydroxy-6-hydroxymethylpteridine inhibit the enzyme activity with the respective Ki values of 2.5×10-5M and 10-5M by competing with the substrate at the active center on the enzyme. These findings suggest that the strong affinity of the formylpteridine for the enzyme correlates profoundly with an oxidized structure of the pyrazine ring substituted with a formyl group at the position 6.
