Biliverdin reductase: characterization in the rat kidney and the inhibition of activity by mercuric chloride.
The effects of metal ions on the activities of biliverdin reductase in the rat kidney and liver were examined; the pH optimum and the cofactor requirement for the enzyme activity in the kidney were also studied. The reduction of biliverdin IX alpha by biliverdin reductase in the rat kidney cytosol fraction could be supported by NADPH and NADH. The activity was optimal around pH 8.7 when NADPH was the cofactor. The activity with NADH was undetectable at this pH. NADH-dependent biliverdin reductase was optimal at pH 7.0, where the NADPH-dependent activity was negligible. Biliverdin reductase activity was not inducible in the kidney or liver in response to treatment of rats with metal ions--Co2+, Ni2+, Pb2+, Sn2+, Zn2+, Cd2+, and Cu2+ or sodium selenite. Rather, both NADPH- and NADH-dependent activities in the kidney were decreased markedly in a time- and dose-related manner following the administration of HgCl2 (10-30 mumoles/kg, 24 hr). The pretreatment of rats (30 min) with sodium selenite (5 mumoles/kg) effectively blocked the Hg2+ (20 mumoles/kg, 24 hr) inhibition of the kidney cytosol biliverdin reductase activity. Similarly, in vitro Hg2+ was an effective inhibitor of the kidney biliverdin reductase. In addition, highly purified biliverdin reductase also was extremely sensitive to Hg2+ and the thiol reagent, 5,5'-dithiobis-(2-nitrobenzoic acid). The inhibition of purified reductase by 5,5'-dithiobis-(2-nitrobenzoic acid), but not by Hg2+, could be reversed by dithiothreitol.
D000818:Animals; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology*; D008627:Mercuric Chloride; D008628:Mercury / Q000494:pharmacology*; D008670:Metals / Q000494:pharmacology; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D044925:Oxidoreductases Acting on CH-CH Group Donors; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000494:pharmacology
D008670:Metals; D009243:NAD; D009249:NADP; D008627:Mercuric Chloride; D010088:Oxidoreductases; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019789:biliverdin reductase; D008628:Mercury; D012643:Selenium