Advertisement

Biological and Biochemical Aspects of ML-236B (Compactin) and Monacolin K, Specific Competitive Inhibitors of 3-hydroxy-3-methylglutaryl Coenzyme A Reductase

  • Akira Endo
Conference paper

Abstract

In anticipation that plasma cholesterol levels may be lowered by inhibiting sterol synthesis in the liver, the major organ that supplies plasma cholesterol, studies aimed at identifying the specific inhibitors of cholesterol synthesis of microbial origin were started in my laboratory in 1971. Since then two novel compounds, ML-236B (compactin) and monacolin K, have been discovered and isolated as low-toxic, potent inhibitors of sterol synthesis from 14C acetate in a cell-free enzyme system of rat liver. This paper briefly reviews biological and biochemical data on these two compounds.

Keywords

Cholesterol Synthesis Familial Hypercholesterolemia Plasma Cholesterol Level Sterol Synthesis Penicillium Citrinum 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Brown MS, Faust JR, Goldstein JL, Kaneko I, End A (1978) Induction of 3-hy-droxy-3-methylglutaryl coenzyme A reductase activity in human fibroblasts incubated with compactin (ML-236B), a competitive inhibitor of the reductase. J Biol Chem 253: 1121–1128PubMedGoogle Scholar
  2. Doi O, End A (1978) Specific inhibition of desmosterol synthesis by ML-236B in mouse LM cells grown in suspension in a lipid-free medium. Japanese J Med Sci Biol 31: 225–233Google Scholar
  3. End A (1979a) Monacolin K, a new hypocholesterolemic agent produced by a Monascus species. J Antibiotics 32: 852–854Google Scholar
  4. End A (1979b) Monacolin K, a new hypocholesterolemic agent that specifically inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase. FEBS Letters, in pressGoogle Scholar
  5. Endo A, Kuroda M, Tsujit Y (1976a) ML-236A, ML-236B, and ML-236C, new inhibitors of cholesterogenesis produced by Penicillium citrinum. J Antibiotics 29: 1346–1348Google Scholar
  6. Endo A, Kuroda M, Tanzaw K (1976b) Competitive inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase by ML-236A and ML-236B, fungal metabolites having hypocholesterolemic activity. FEBS Letters 72: 323–326PubMedCrossRefGoogle Scholar
  7. Endo A, Tsujita Y, Kuroda M, Tanzaw K (1977) Inhibition of in vitro and in vivo cholesterol synthesis by ML-236A and ML-236B, competitive inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Eur J Biochem 77: 31–36PubMedCrossRefGoogle Scholar
  8. Endo A, Tsujita Y, Kuroda M, Tanzaw K (1979) Effects of ML-236B on cholesterol metabolism in mice and rats: lack of hypocholesterolemic activity in normal animals. Biochim Biophys Acta, in pressGoogle Scholar
  9. Kaneko I, Hazama-Shimada Y, End A (1978) Effects of ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on the lipid metabolism in cultured cells. Eur J Biochem 87: 313–321PubMedCrossRefGoogle Scholar
  10. Kuroda M, Tanzawa K, Tsujita Y, End A (1977) Mechanism for elevation of hepatic cholesterol synthesis and serum cholesterol levels in Triton WR-1339-induced hyperlipidemia. Biochim Biophys Acta 489: 119–125PubMedGoogle Scholar
  11. Kuroda M, Tsujita Y, Tanzawa K, End A (1979) Hypolipidemic effects in monkeys of ML-236B, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Lipids 14: 585–589PubMedCrossRefGoogle Scholar
  12. Tanzawa K, End A (1979) Kinetic analysis of the reaction catalyzed by 3-hydroxy-3-methylglutaryl coenzyme A reductase using two specific inhibitors. Eur J Biochem 98: 195–201PubMedCrossRefGoogle Scholar
  13. Tsujita Y, Kuroda M, Tanzawa K, Kitano N, End A (1979) Hypolipidemic effects in dogs of ML-236B, a competitive inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase. Atherosclerosis 32: 307–313PubMedCrossRefGoogle Scholar
  14. Yamamoto A, Sudo H, End A (1979) Therapeutic effects of ML-236B in primary hypercholesterolemia. Atherosclerosis, in pressGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1980

Authors and Affiliations

  • Akira Endo

There are no affiliations available

Personalised recommendations