Work

On the Mechanism of Inactivation of Xanthine Oxidase by Allopurinol and Other Pyrazolo[3,4-d]pyrimidines

Year: 1970

Type: article

Abstract: Allopurinol and other 6-unsubstituted pyrazolo[3,4-d]-pyrimidines have been shown to reduce all of the oxidation-reduction reactive groups of milk xanthine oxidase. The great inhibitory action of these compounds has been shown to be due to a sort of suicide reaction, in which the product formed by enzymatic hydroxylation in position 6 is joined in complex with a partially reduced from of the enzyme. Several lines of evidence are presented indicating that complex formation is with the enzyme-bound molybdenum in the Mo(IV) state. Studies on the stoichiometry of binding of the product of allopurinol reaction, allo-xanthine(4,6-dihydroxypyrazolo[3,4-d]pyrimidine), revealed that the amount of allo-xanthine bound was proportional to the percentage of functional active sites in the enzyme preparation; i.e. it serves as an active site label. From these results it is concluded that the best preparations of xanthine oxidase so far obtained contain only 75 to 80% functional active sites, even though they possess their full complement of flavin, molybdenum, and iron-sulfur components. Evidence is presented that the presence of nonfunctional active sites is responsible for several of the slow reactions previously observed with the enzyme.

Source: Journal of Biological Chemistry

DOI: 10.1016/s0021-9258(18)63065-0

Authors: Vincent Massey, Hirochika Komai, Graham Palmer, Gertrude B. Elion

Institutions: University of Michigan, Wellcome Trust

Language: English

Topic: Biochemical and Molecular Research

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,430