Inhibition studies of bovine xanthine oxidase by luteolin, silibinin, quercetin, and curcumin.
Xanthine oxidoreductase (XOR) is a molybdenum-containing enzyme that under physiological conditions catalyzes the final two steps in purine catabolism, ultimately generating uric acid for excretion. Here we have investigated four naturally occurring compounds that have been reported to be inhibitors of XOR in order to examine the nature of their inhibition utilizing in vitro steady-state kinetic studies. We find that luteolin and quercetin are competitive inhibitors and that silibinin is a mixed-type inhibitor of the enzyme in vitro, and, unlike allopurinol, the inhibition is not time-dependent. These three natural products also decrease the production of superoxide by the enzyme. In contrast, and contrary to previous reports in the literature based on in vivo and other nonmechanistic studies, we find that curcumin did not inhibit the activity of purified XO nor its superoxide production in vitro.
Pauff
James M
JM
Department of Biochemistry, University of California, Riverside, California 92521, USA.
Hille
Russ
R
D000818:Animals; D002417:Cattle; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D047311:Luteolin / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D008982:Molybdenum / Q000737:chemistry / Q000378:metabolism; D011687:Purines / Q000378:metabolism; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology*; D000077385:Silybin; D012838:Silymarin / Q000737:chemistry / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D019820:Xanthine / Q000737:chemistry / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D011687:Purines; D012838:Silymarin; D013481:Superoxides; D019820:Xanthine; D000077385:Silybin; D008982:Molybdenum; D011794:Quercetin; D014969:Xanthine Oxidase; D003474:Curcumin; D047311:Luteolin