Demonstration of 26-hydroxylation of C27-steroids in human skin fibroblasts, and a deficiency of this activity in cerebrotendinous xanthomatosis.
Demonstration of 26-hydroxylation of C27-steroids in human skin fibroblasts, and a deficiency of this activity in cerebrotendinous xanthomatosis.
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证明人皮肤成纤维细胞中 C27-类固醇的 26-羟基化，以及脑腱黄瘤病中缺乏这种活性。
DOI：
10.1172/jci112633
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Grundy,S
中科院分区：
文献类型：
--
作者：
Skrede,S;Bjorkhem,I;Kvittingen,EA;Buchmann,MS;Lie,SO;East,C;Grundy,S
26-在来自健康个体的培养的皮肤成纤维细胞中证实了5 β-胆甾烷-3 α，7 α，12 α-三醇和其他C27-类固醇的羟基化。在皮肤成纤维细胞中的活性约为先前在人肝匀浆中发现的活性的5-10%，并且被CO抑制。表观Km对于5 β-胆甾烷-3 α，7 α，12 α-三醇（1.3 μ mol/L）最低，对于5-己烯-3 β，7 α-二醇（12 μ mol/L）最高。7 α-羟基-4-异戊烯-3-酮的26-羟基化速率最高。这些特征与肝线粒体C27-类固醇26-羟化酶的特征相似。在三名肌腱黄瘤病（CTX）患者的皮肤成纤维细胞中，C27-类固醇的26-羟基化仅以健康对照的0.2-2.5%的速率进行。在这些细胞中未证实内源性5 β-胆甾烷-3 α，7 α，12 α-三醇的蓄积，并且放射性26-羟基化产物的形成降低不能通过稀释标记的外源性底物来解释。目前的结果增加了强有力的证据的概念，在CTX的主要代谢缺陷是C27-类固醇26-羟化酶的缺陷。
26-Hydroxylation of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol and other C27-steroids was demonstrated in cultured skin fibroblasts from healthy individuals. Activities in skin fibroblasts were approximately 5-10% of those previously found in human liver homogenates, and were inhibited by CO. The apparent Km was lowest for 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol (1.3 mumol/liter) and highest for 5-cholestene-3 beta, 7 alpha-diol (12 mumol/liter). The rate of 26-hydroxylation was highest with 7 alpha-hydroxy-4-cholesten-3-one. These characteristics are similar to those of hepatic mitochondrial C27-steroid 26-hydroxylase. In skin fibroblasts from three patients with cerebrotendinous xanthomatosis (CTX), 26-hydroxylation of C27-steroids proceeded at a rate of only 0.2-2.5% of healthy controls. No accumulation of endogenous 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol could be demonstrated in these cells, and the lowered formation of radioactive, 26-hydroxylated products could not be explained by dilution of the labeled exogenous substrate. The present results add strong evidence to the concept that the primary metabolic defect in CTX is a deficiency of C27-steroid 26-hydroxylase.