Abnormal NADPH-cytochrome P-450 reductase in the liver microsomes of riboflavin-deficient rats

Abstract

When rats were kept on a riboflavin-deficient diet, NADPH-cytochrome c and NADPH-ferricyanide reductase activities of the liver microsomes (deficient microsomes) decreased to 27% and 40% of the corresponding controls. To elucidate the unbalanced decrease of these activities in deficient microsomes, enzymological and immunochemical properties of the NADPH-cytochrome P-450 reductase in the liver microsomes of riboflavin-deficient rats were compared with those of control rats. Judging from quantitative immunoprecipitation, the amount of the reductase protein in the deficient microsomes was 67% of control, whereas the FAD and FMN contents in the immunoprecipitates were 110% and 59% of control, respectively. When the reductase was purified from the deficient microsomes, it contained 18.0 and 10.9 nmoles of FAD and FMN, respectively, per mg of protein, while the control enzyme contained 14.5 and 14.3 nmoles of the flavins, respectively. These and other lines of evidence suggest the existence of an abnormal NADPH-cytochrome P-450 reductase, having unbalanced contents of FAD and FMN, in deficient microsomes.