Turnover of membrane proteins: kinetics of induction and degradation of seven forms of rat liver microsomal cytochrome P-450, NADPH-cytochrome P-450 reductase, and epoxide hydrolase.
The in vivo turnover of several rat liver microsomal proteins was studied using techniques designed to maximize antibody recognition specificity and minimize reutilization of radioactive labels. The kinetics of degradation of seven cytochrome P-450 isozymes, NADPH-cytochrome P-450 reductase, and epoxide hydrolase were determined in untreated rats and rats treated with phenobarbital or beta-naphthoflavone. In the cases where induction of these enzymes occurred with the above chemicals, rates of synthesis of the proteins were also estimated. In general, the degradation rates of the different proteins were rather similar to each other, and the effects of phenobarbital and beta-naphthoflavone on these rates were not very great. However, in the case of cytochromes P-450, a general trend was observed in which the heme moiety was degraded more rapidly than the apoprotein. Changes in the rates of synthesis of the individual proteins appear to contribute more to the altered steady-state levels which are expressed than do the rates of degradation, and profiles of steady-state enzyme concentrations predicted by the kinetic constants approximate those observed in vivo.
D000818:Animals; D001571:Benzoflavones / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004851:Epoxide Hydrolases / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D019324:beta-Naphthoflavone
D001571:Benzoflavones; D008565:Membrane Proteins; D019324:beta-Naphthoflavone; D003577:Cytochrome P-450 Enzyme System; D009251:NADPH-Ferrihemoprotein Reductase; D004851:Epoxide Hydrolases; D010634:Phenobarbital