Inhibition of xanthine oxidase and related enzymes by 6-pteridyl aldehyde.

We have recently reported’ the inhibition of xanthopterin oxidase and xanthine oxidase by synthetic pteroylglutamic acid (PGA). However, since an exceptionally pure sample2 of PGA, which was later examined, possessed less than one-sixth of the inhibitory power previously observed, it appears possible that the effect is due to traces of a contaminant. The observation by Lowry and Bessey3 that 2-amino-4-hydroxy-6-pteridyl aldehyde, a primary photofission product of PGA, strongly inhibits pteridine oxidase suggests that this aldehyde may be the active inhibitor in the above enzyme systems. We have now found that the 6-pteridyl aldehyde, prepared by hydrolysis of PGA in sulfurous acid,4 is on a molar basis 200 to 400 times more active as an inhibitor of xanthine oxidase (i.e. 0.005 to 0.02 y per ml.) than the folic acid preparations previously studied.’ A number of other oxidases related to xanthine oxidase are also strongly inhibited by 6-pteridyl aldehyde. It was mentioned that Lowry found that the enzymic oxidation of 2-amino-4-hydroxypteridine to isoxanthopterin is inhibited by minute amounts of the pteridyl aldehyde. Xanthopterin oxidase from milk and liver is likewise inhibited by small amounts of pteridyl aldehyde. This substance exerts also a strong effect on quinine oxidase from rabbit liver.6 A concentration of 0.4 y of pteridyl aldehyde per ml. reduces the quinine oxidase activity to about 30 per cent of that of the uninhibited sample. This observation may have pharmacological interest inasmuch as human liver is reported to contain quinine oxidase. Uricase and triose phosphate oxidase were not inhibited by the addition of pteridyl aldehyde. The potency of 6-pteridyl aldehyde as an inhibitor is lost by addition of 2,4-dinitrophenylhydrazine which reacts with the free aldehyde group.