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J Nutr. 2002 Jun;132(6):1129-34.

S-alk(en)yl cysteines of garlic inhibit cholesterol synthesis by deactivating HMG-CoA reductase in cultured rat hepatocytes.

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1
Nutrition Department, The Pennsylvania State University, University Park, PA 16802, USA.

Abstract

The effects of water-soluble organosulfur compounds of garlic on hepatic cholesterol biosynthesis in cultured rat hepatocytes were studied. S-Alk(en)yl cysteines, i.e., S-allyl cysteine (SAC), S-ethyl cysteine (SEC) and S-propyl cysteine (SPC) inhibited cholesterol synthesis from [(14)C]acetate but not from [(14)C]mevalonate. The activity of 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase in the cells treated with SAC, SEC and SPC was 30-40% lower than that of the untreated cells. S-Alk(en)yl cysteines did not alter abundance of mRNA coded for HMG-CoA reductase or protein concentration of the enzyme. The ratio of expressed to total activity (E/T) of HMG-CoA reductase was then determined as an index of phosphorylation status of the enzyme. The E/T ratio was reduced 18-29% by SAC, SEC and SPC, resulting primarily from decreased expressed activity. The results suggest that S-alk(en)yl cysteines inhibit cholesterol synthesis by deactivating HMG-CoA reductase via enhanced phosphorylation, but not changing levels of mRNA or the amount of the enzyme. Additionally, of the three S-alk(en)yl cysteines tested, only SAC appears to further decrease the activity of HMG-CoA reductase by increasing sulfhydryl oxidation of the enzyme.

PMID:
12042421
DOI:
10.1093/jn/132.6.1129
[Indexed for MEDLINE]

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