Three forms of xanthine: acceptor oxidoreductase in rat heart.
The enzyme xanthine: acceptor oxidoreductase found in rat heart equilibrates between three forms differing in electron acceptor specificity. Form D transfers electrons exclusively to NAD+ and accounts for 85% of total oxidoreductase activity. Form O transfers electrons to molecular oxygen and accounts for 8%. The D/O form prefers NAD+, but without NAD+ transfers electrons to oxygen. Interconversion from D to O and O to D forms is catalyzed by sulfhydryl group-modifying reagents: Cd2+, Cu2+, disulfiram, and heating with dithiothreitol. This suggests that sulfhydryl groups participate in the first stage of enzyme conversion. The NADH/NAD+ concentration ratio may regulate the dehydrogenase activity of xanthine:acceptor oxidoreductase (NAD+-dependent activity of D and D/O forms). Accumulating NADH inhibits hypoxanthine hydroxylation. The amount of form O increases during cardiac ischemia, facilitating superoxide radical-ion generation. Also, NADH/NAD+ does not regulate form O, promoting adenylate nucleotide pool depletion, especially in the heart which has low de novo purine nucleotide synthesis.
Kaminski
Z W
ZW
Pohorecki
R
R
Ballast
C L
CL
Domino
E F
EF
D000818:Animals; D006900:Hydroxylation; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D066298:In Vitro Techniques; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D009243:NAD / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014968:Xanthine Dehydrogenase / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000378:metabolism*
D007042:Hypoxanthines; D009243:NAD; D019271:Hypoxanthine; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D007658:Ketone Oxidoreductases