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人体中酯化胆固醇在脂蛋白之间以及向肝脏和胆汁转移的体内评估。

An in vivo evaluation in man of the transfer of esterified cholesterol between lipoproteins and into the liver and bile.

作者信息

Schwartz C C, Vlahcevic Z R, Halloran L G, Swell L

出版信息

Biochim Biophys Acta. 1981 Jan 26;663(1):143-62. doi: 10.1016/0005-2760(81)90201-0.

DOI:10.1016/0005-2760(81)90201-0
PMID:7011409
Abstract

The metabolism of the esterified cholesterol fractions of HDL and LDL has been studied in vivo in man with regard to their ability to serve as precursors (after intrahepatic hydrolysis) for bile acid synthesis and biliary cholesterol secretion. Information was also obtained on the exchange of cholesterol esters between the lipoprotein classes. Fasting subjects were intravenously administered autologous HDL (or LDL) labeled with esterified [3H]cholesterol and free [3H]- and [14C]cholesterol. Following the administration of the labeled lipoproteins, bile and blood were collected at frequent intervals. In each experiment the observed 3H/14C ratios in bile acids, biliary cholesterol, lipoprotein free cholesterol and red blood cell cholesterol were similar and markedly divergent from the lipoprotein esterified cholesterol 3H/14C ratios. Following the administration of labeled HDL, the 3H/14C ratios observed in the esterified cholesterol fractions of VLDL and LDL closely resembled the ratios in HDL indicating that VLDL and LDL received esterified cholesterol by direct transfer from HDL. Following the administration of labeled LDL, the 3H/14C ratios in HDL esterified cholesterol were midway between the ratio in LDL esterified cholesterol and plasma free cholesterol, indicating that HDL esterified cholesterol is derived from more than one source. These sources could be LDL esterified cholesterol and esters formed de novo from plasma free cholesterol. A precursor-product relationship was found between the specific activities of lipoprotein free cholesterol and the bile steroids. Assuming direct entry of lipoprotein free and esterified cholesterol (after hydrolysis) into the bile acid and biliary cholesterol precursor pools, it was calculated that less than 20% of these biliary steroids could be derived from HDL esterified cholesterol. The results support the view that lipoprotein free cholesterol is the major source of bile acids in man. Also, the results suggest that in vivo esterified cholesterol fractions of VLDL and LDL originate from HDL, that some LDL ester is transferred back to HDL, and that the cholesterol liberated form hydrolyzed esters undergoes recirculation into the free cholesterol pool rather than excretion as biliary cholesterol or bile acids.

摘要

关于高密度脂蛋白(HDL)和低密度脂蛋白(LDL)中酯化胆固醇部分作为胆汁酸合成和胆汁胆固醇分泌的前体(肝内水解后)的能力,已在人体进行了体内研究。还获得了关于脂蛋白类别之间胆固醇酯交换的信息。对空腹受试者静脉注射用酯化[3H]胆固醇以及游离[3H]和[14C]胆固醇标记的自体HDL(或LDL)。注射标记的脂蛋白后,频繁采集胆汁和血液。在每个实验中,胆汁酸、胆汁胆固醇、脂蛋白游离胆固醇和红细胞胆固醇中观察到的3H/14C比值相似,且与脂蛋白酯化胆固醇的3H/14C比值明显不同。注射标记的HDL后,极低密度脂蛋白(VLDL)和LDL的酯化胆固醇部分中观察到的3H/14C比值与HDL中的比值非常相似,表明VLDL和LDL通过从HDL的直接转移获得酯化胆固醇。注射标记的LDL后,HDL酯化胆固醇中的3H/14C比值介于LDL酯化胆固醇和血浆游离胆固醇的比值之间,表明HDL酯化胆固醇来自多个来源。这些来源可能是LDL酯化胆固醇和由血浆游离胆固醇重新合成的酯。发现脂蛋白游离胆固醇的比活性与胆汁类固醇之间存在前体-产物关系。假设脂蛋白游离和酯化胆固醇(水解后)直接进入胆汁酸和胆汁胆固醇前体池,经计算,这些胆汁类固醇中不到20%可来自HDL酯化胆固醇。结果支持脂蛋白游离胆固醇是人体胆汁酸主要来源的观点。此外,结果表明,在体内VLDL和LDL的酯化胆固醇部分起源于HDL,一些LDL酯被转移回HDL,并且从水解酯中释放的胆固醇再循环进入游离胆固醇池,而不是作为胆汁胆固醇或胆汁酸排泄。

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