Key result
Glutathione-deficient fibroblasts exhibited HMG-CoA reductase activities lower than or comparable to control preparations, indicating only a partial reduction in cholesterol synthesis capacity.
Why the study?
Does glutathione deficiency reduce HMG-CoA reductase activity and cholesterol synthesis capacity in cultured fibroblasts?
Does glutathione deficiency reduce HMG-CoA reductase activity and cholesterol synthesis capacity in cultured fibroblasts?
Glutathione deficiency causes only a modest reduction in HMG-CoA reductase activity, suggesting alternative in vivo activation mechanisms for cholesterol synthesis exist.
Hypothesis-generating for glutathione's limited role in cholesterol synthesis; leaves open alternative in vivo mechanisms before any clinical relevance.
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.
No takes yet. Share an insight, caveat, or question.
Gustafsson et al. (1990) studied Glutathione deficiency. Glutathione deficiency vs. Normal/healthy fibroblasts was evaluated on HMG-CoA reductase activity. Glutathione-deficient fibroblasts exhibited HMG-CoA reductase activities lower than or comparable to control preparations, indicating only a partial reduction in cholesterol synthesis capacity.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: