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

J Nutr. 2002 Jun;132(6):1129-34. doi: 10.1093/jn/132.6.1129.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticholesteremic Agents / pharmacology
  • Carbon Isotopes
  • Cells, Cultured
  • Cholesterol / biosynthesis*
  • Cysteine / analogs & derivatives*
  • Cysteine / pharmacology*
  • Garlic* / chemistry
  • Hepatocytes / drug effects
  • Hepatocytes / enzymology*
  • Hydroxymethylglutaryl CoA Reductases / genetics
  • Hydroxymethylglutaryl CoA Reductases / metabolism*
  • Immunoblotting
  • Male
  • Phosphorylation
  • RNA, Messenger / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction


  • Anticholesteremic Agents
  • Carbon Isotopes
  • RNA, Messenger
  • Cholesterol
  • Hydroxymethylglutaryl CoA Reductases
  • Cysteine