Kandutsch A A, Chen H W
J Cell Physiol. 1975 Apr;85(2 Pt 2 Suppl 1):415-24. doi: 10.1002/jcp.1040850408.
Sterol synthesis in liver in vivo is regulated at the site of the reaction catalyzed by 3-hydroxy-3-methylglutaryl-CoA reductase through a feedback system thought to involve either cholesterol or one or more of the products of its metabolism. Cholesterol feeding results in repression of the synthesis of the enzyme, but inactivation of the enzyme seems to precede repressroblasts is not inhibited by purified exogenous cholesterol. However, derivatives of cholesterol produced by the introduction of a ketone or hydroxyl function in the 7, 20, 22 or 25 positions effectively inhibit sterol synthesis by specifically depressing the level of HMG CoA reductase activity. As a result of this specific effect prolonged incubation of an inhibitory sterol with growing L cells results in depletion of cellular sterol. Growth of the culture then ceases and the cells die unless an appropriate sterol or a sterol precursor is supplied in the medium. The inhibitory sterols, 25-hydroxycholesterol and 7-ketocholesterol appear to be taken up by L cells through processes that involve their specific interactions with saturable cellular receptors. The uptake of cholesterol by L cells appears to be by a different process--possibly through physical diffusion.
体内肝脏中的甾醇合成在由3-羟基-3-甲基戊二酰辅酶A还原酶催化的反应位点受到调节，通过一种反馈系统，该系统被认为涉及胆固醇或其代谢的一种或多种产物。喂食胆固醇会导致该酶合成的抑制，但酶的失活似乎先于抑制作用。成纤维细胞不受纯化的外源胆固醇抑制。然而，通过在7、20、22或25位引入酮或羟基功能而产生的胆固醇衍生物通过特异性降低HMG CoA还原酶活性水平而有效抑制甾醇合成。由于这种特异性作用，将抑制性甾醇与生长中的L细胞长时间孵育会导致细胞甾醇耗竭。除非在培养基中提供适当的甾醇或甾醇前体，否则培养物的生长随后会停止且细胞死亡。抑制性甾醇25-羟基胆固醇和7-酮胆固醇似乎通过涉及它们与可饱和细胞受体的特异性相互作用的过程被L细胞摄取。L细胞摄取胆固醇似乎是通过不同的过程——可能是通过物理扩散。
