Kinetic parameters for high density lipoprotein apoprotein AI and cholesteryl ester transport in the hamster.

Kinetic parameters for high density lipoprotein apoprotein AI and cholesteryl ester transport in the hamster.
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仓鼠中高密度脂蛋白脱辅基蛋白 AI 和胆固醇酯转运的动力学参数。

DOI:
10.1172/jci119334
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发表时间:
1997
期刊:
The Journal of clinical investigation.
影响因子:
--
通讯作者:
Spady,DK
Spady,DK
中科院分区:
--
文献类型:
--
作者:
Woollett,LA;Spady,DK

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这些研究是为了确定仓鼠体内高密度脂蛋白(HDL)载脂蛋白AI和胆固醇酯转运的动力学特征。在肾脏、肾上腺和肝脏中证实了饱和HDL载脂蛋白AI转运。饱和HDL胆固醇酯转运在肾上腺和肝脏中最高。在肝脏和肾上腺中,蛋白质和胆固醇酯部分的受体依赖性摄取的最大转运速率(J(m))相似;然而,apo AI达到半数最大转运所需的HDL浓度(K(m))高20- 30倍。因此,在正常血浆HDL浓度下,HDL胆固醇酯的清除率在肾上腺中超过HDL载脂蛋白AI约10倍,在肝脏中超过约5倍。在正常HDL浓度下,大部分HDL胆固醇酯(76%)被肝脏清除,而大部分HDL载脂蛋白AI(77%)被肝外组织清除。肝脏摄取HDL胆固醇酯的速率等于所有肝外组织摄取胆固醇的速率,表明肝脏摄取HDL胆固醇酯准确反映了“胆固醇逆向转运”的速率。“受体依赖性HDL胆固醇酯在正常血浆HDL浓度下被肝脏摄取最大(饱和)。因此,血浆HDL浓度的变化并不伴随着HDL胆固醇酯向肝脏递送的平行变化,除非转运蛋白的数量或亲和力也受到调节。
These studies were undertaken to determine the kinetic characteristics of high density lipoprotein (HDL) apo AI and cholesteryl ester transport in the hamster in vivo. Saturable HDL apo AI transport was demonstrated in the kidneys, adrenal glands, and liver. Saturable HDL cholesteryl ester transport was highest in the adrenal glands and liver. In the liver and adrenal glands, maximal transport rates (J(m)) for receptor dependent uptake were similar for the protein and cholesteryl ester moieties; however, the concentration of HDL necessary to achieve half-maximal transport (K(m)) was 20- to 30-fold higher for apo AI. Consequently, at normal plasma HDL concentrations, the clearance of HDL cholesteryl ester exceeded that of HDL apo AI by approximately 10-fold in the adrenal glands and by approximately fivefold in the liver. At normal HDL concentrations, the majority of HDL cholesteryl ester (76%) was cleared by the liver whereas the majority of HDL apo AI (77%) was cleared by extrahepatic tissues. The rate of HDL cholesteryl ester uptake by the liver equaled the rate of cholesterol acquisition by all extrahepatic tissues suggesting that HDL cholesteryl ester uptake by the liver accurately reflects the rate of "reverse cholesterol transport." Receptor dependent HDL cholesteryl ester uptake by the liver was maximal (saturated) at normal plasma HDL concentrations. Consequently, changes in plasma HDL concentrations are not accompanied by parallel changes in the delivery of HDL cholesteryl ester to the liver unless the number or affinity of transporters is also regulated.