Feingold K R, Wiley M H, MacRae G, Siperstein M D
J Lipid Res. 1981 Aug;22(6):990-7.
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.
导致胆固醇生成的甾醇途径和产生二氧化碳的分流途径。肾脏是这两种途径对循环中甲羟戊酸进行代谢的主要部位。本研究调查了血浆胆固醇浓度对循环中甲羟戊酸代谢的影响。利用3-氨基吡唑并(3,4-d)嘧啶和吐温WR 1339诱导“功能性低胆固醇血症”。当用这两种化合物诱导“功能性低胆固醇血症”时，观察到循环中甲羟戊酸的肾脏总不皂化脂质合成（增加36%-43%）和胆固醇合成（增加42%）均增强。在经吐温处理的动物中，循环中甲羟戊酸的肝脏总不皂化脂质合成未增强，但4-氨基吡唑并(3,4-d)嘧啶处理增加了总标记不皂化脂质和胆固醇的积累。用这两种化合物处理后，在胴体中未观察到标记的总不皂化脂质或胆固醇增加。“功能性低胆固醇血症”使循环中甲羟戊酸代谢的分流途径减少约30%。这种减少发生在肾脏和肾外分流途径中。这些数据表明，血浆胆固醇浓度调节循环中甲羟戊酸的体内代谢，即低胆固醇血症减少分流途径并刺激甾醇生成，且这种作用主要局限于肾脏。
