Journal of Lipid Research, Vol 22, 990-997, Copyright © 1981 by Lipid Research, Inc.
The effect of decreased plasma cholesterol concentration on circulatinga mevalonate metabolism in rats
KR Feingold, MH Wiley, G MacRae and MD Siperstein
Circulating mevalonate is metabolized by two mechanisms: the sterol
pathways leading to cholesterol and the shunt pathway resulting in CO2
production. The kidney is the chief site of circulating mevalonate
metabolism by both pathways. The present study investigated the effect of
plasma cholesterol concentration on circulating mevalonate metabolism.
3-Aminopyrazolo(3,4-d)pyrimidine and Triton WR 1339 were utilized to induce
"functional hypocholesterolemia". An enhancement of both renal total
nonsaponifiable lipid synthesis (36-43%) and cholesterol synthesis (42%)
from circulatinga mevalonate was observed when "functional
hypocholesterolemia" was induced by either compound. Hepatic total
nonsaponifiable lipid synthesis from circulating mevalonate was not
enhanced in the Triton-treated animals, but 4-
aminopyrazolo(3,4-d)pyrimidine treatment increased accumulation of total
labeled nonsaponifiable lipids and cholesterol. No increase in labeled
total nonsaponifiable lipids or cholesterol in the carcass was observed
after treatment with wither compound. "Functional hypocholesterolemia"
reduced the shunt pathway of circulating mevalonate metabolism by
approximately 30%. This reduction occurred in both the renal and extrarenal
shunt pathways. These data indicate that plasma cholesterol concentration
regulates the in vivo metabolism of circulating mevalonate in that
hypocholesterolemia reduces the shunt pathway and stimulates
sterologenesis, and effect chiefly localized to athe kidneys.
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