Gustafsson J, Carlsson B, Larsson A
Department of Paediatrics, University of Uppsala, Sweden.
Eur J Clin Invest. 1990 Aug;20(4):470-4. doi: 10.1111/j.1365-2362.1990.tb01886.x.
3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase catalyses the rate-limiting step in cholesterol synthesis. Glutathione (GSH) has been postulated to be an important activator of HMG-CoA reductase in vivo. HMG-CoA reductase activity was assayed in cultured fibroblasts from healthy children. Solubilized enzyme preparations were prepared by ultracentrifugation after freezing and thawing of fibroblasts. Such treatment increased the relative enzyme activity markedly. Enzymological assay conditions were established. Addition of GSH stimulated the reaction, whereas there was inhibition after addition of glutathione disulphide (GSSG). The inhibitory effect of GSSG could be reversed by the addition of excess GSH. Fibroblast preparations, deficient in GSH, were obtained from children with glutathione synthetase deficiency or from normal subjects after the growth of fibroblasts in the presence of buthionine sulphoximine. Solubilized enzyme preparations from GSH-deficient fibroblasts had HMG-CoA reductase activities lower than or comparable with those of control preparations. The results indicate only some reduction in the capacity for cholesterol synthesis in subjects with glutathione deficiency. The existence of additional activation mechanisms in vivo, alternative to GSH, for thiol-dependent modulation of HMG-CoA reductase activity seems likely.
3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶催化胆固醇合成中的限速步骤。谷胱甘肽（GSH）被认为是体内HMG-CoA还原酶的重要激活剂。对健康儿童培养的成纤维细胞中的HMG-CoA还原酶活性进行了测定。成纤维细胞经冻融后通过超速离心制备可溶性酶制剂。这种处理显著提高了相对酶活性。建立了酶学测定条件。添加GSH刺激反应，而添加谷胱甘肽二硫化物（GSSG）后则产生抑制作用。添加过量的GSH可逆转GSSG的抑制作用。谷胱甘肽合成酶缺乏症患儿或在丁硫氨酸亚砜胺存在下培养成纤维细胞后的正常受试者的成纤维细胞制剂中GSH缺乏。GSH缺乏的成纤维细胞的可溶性酶制剂的HMG-CoA还原酶活性低于或与对照制剂相当。结果表明，谷胱甘肽缺乏的受试者胆固醇合成能力仅略有降低。体内似乎存在除GSH之外的其他激活机制，用于硫醇依赖性调节HMG-CoA还原酶活性。
