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Cholesterol synthesis in patients with glutathione deficiency
Author(s) -
GUSTAFSSON J.,
CARLSSON B.,
LARSSON A.
Publication year - 1990
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1990.tb01886.x
Subject(s) - glutathione , reductase , glutathione reductase , chemistry , hmg coa reductase , in vivo , coenzyme a , hydroxymethylglutaryl coa reductase , enzyme , buthionine sulfoximine , biochemistry , glutaredoxin , thiol , glutathione disulfide , enzyme assay , activator (genetics) , endocrinology , medicine , biology , glutathione peroxidase , microbiology and biotechnology , gene
. 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 ultracentrifu‐gation 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.,