Metabolism of plasma mevalonate in rats and humans.
A circadian rhythm in plasma mevalonate was identified in human subjects. This variation, over a 5-fold range, is paralleled by a rhythm in urinary excretion. No such diurnal change in plasma mevalonate was observed in schedule-fed, light-cycled rats, despite the presence of a pronounced rhythm in liver HMG-Coa reductase and sterol synthesis. A linear correlation was found between liver HMG-CoA reductase activity and the rate of hepatic sterol synthesis. Sterol synthesis accounted for 59% of the HMG-CoA reductase activity. A 4-fold increase in plasma mevalonate following bilateral nephrectomy did not feed back on liver HMG-CoA reductase. Turnover rates for circulating R- and S-mevalonate were determined by the kinetics of tritiated tracers. S-Mevalonate exhibited first-order kinetics with a T 1/2 of 19 to 23 min, while R-mevalonate kinetics could be resolved into two phases with half-lives of 9 and 42 min. The renal uptake of circulating mevalonate was measured by the initial rate of increase in plasma mevalonate immediately following bilateral nephrectomy; this was confirmed by determination of the renal arterio-venous difference. This value ranges between 500 and 600 pmol/min for a 250-g rat.
D000328:Adult; D000818:Animals; D005215:Fasting; D005260:Female; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008798:Mevalonic Acid / Q000097:blood* / Q000652:urine; D008862:Microsomes, Liver / Q000201:enzymology; D009392:Nephrectomy; D010507:Periodicity; D051381:Rats; D011919:Rats, Inbred Strains
D006903:Hydroxymethylglutaryl CoA Reductases; D008798:Mevalonic Acid