Control of sterol metabolism in rat adrenal mitochondria.
Control of sterol metabolism in rat adrenal mitochondria.
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大鼠肾上腺线粒体甾醇代谢的控制。
DOI：
10.1042/bj1741045
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发表时间：
1978
期刊：
影响因子：
--
通讯作者：
G. S. Boyd
中科院分区：
文献类型：
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作者：
J. Mason;J. Arthur;G. S. Boyd
促肾上腺皮质激素（ACTH）刺激肾上腺线粒体从内源性前体合成类固醇，并对蛋白质合成抑制剂放线菌酮敏感。在本研究中，研究了放线菌酮处理对大鼠肾上腺线粒体代谢正常类固醇生成底物（即胆固醇）的一些类似物的影响。观察到类似物如链甾醇、26-去甲胆甾-5-烯-3 β-醇和5-胆烯-3 β-醇（即具有非极性烷基侧链，如胆固醇）的代谢对放线菌酮处理敏感。相比之下，侧链上具有极性基团的那些类似物，即，20 α-、24-、25-和26-羟基胆固醇对放线菌酮预处理不敏感。研究了添加的甾醇与线粒体甾醇碳链酶的细胞色素P-450组分的结合。还对加入外源甾醇以达到最大的双烯醇酮生产速率的平衡时间进行了类似的研究。这两项研究表明，胆固醇，一种非极性甾醇，缓慢渗透通过线粒体环境到达细胞色素P-450反应中心，而24-和26-羟基胆固醇迅速达到酶环境。甾醇代谢中的环己酰亚胺敏感过程似乎与线粒体内的非极性甾醇（如胆固醇）转移到靠近酶的区域有关。的重要性，和可能的作用机制，环己酰亚胺敏感因子在控制肾上腺类固醇的生成进行了讨论。
Steroidogenesis by adrenal mitochondria from endogenous precursors is stimulated by corticotropin (ACTH) and is sensitive to the protein-synthesis inhibitor cycloheximide. In the present investigation the effect of cycloheximide treatment on the metabolism of a number of analogues of the normal steroidogenic substrate, i.e. cholesterol, by rat adrenal mitochondria was studied. It was observed that the metabolism of analogues such as desmosterol, 26-norcholest-5-en-3beta-ol and 5-cholen-3beta-ol (that is with non-polar alkyl side chains like cholesterol), was sensitive to cycloheximide treatment. By contrast, the metabolism of those analogues with polar groupings on the side chain, i.e., 20alpha-, 24-, 25- and 26-hydroxycholesterols was insensitive to pretreatment with cycloheximide. The binding of added sterol to the cytochrome P-450 component of the mitochondrial sterol desmolase was studied. Similar studies on the equilibration time on addition of exogenous sterols to achieve maximum rates of pregnenolone production were also made. Both studies show that cholesterol, a non-polar sterol, penetrated slowly through the mitochondrial milieu to reach the cytochrome P-450 reaction centre whereas 24- and 26-hydroxycholesterols rapidly attained the enzymic environment. The cycloheximide-sensitive process in sterol metabolism appeared related to the transfer of non-polar sterols such as cholesterol within the mitochondria to a region in close proximity to the enzyme. The importance, and possible mechanism of action, of the cycloheximide-sensitive factor in the control of adrenal steroidogenesis is discussed.