COMPETITIVE INHIBITION OF 3-HYDROXY-3-METHYLGLUTARYL COENZYME A REDUCTASE BY ML-236A AND ML-236B FUNGAL METABOLITES, HAVING HYPOCHOLESTEROLEMIC ACTIVITY

4区 · 医学

Article

作者: Endo, Akira ; Kuroda, Masao ; Tanzawa, Kazuhiko

Fungal metabolites, ML-236A and ML-236B, were isolated from cultures of Penicillium citrinum as potent inhibitors of cholesterol synthesis in vitro.It was shown that ML-236A and ML-236B inhibit specifically 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase, the rate limiting enzyme in cholesterol synthetic pathway, without affecting the rest of the enzymes involved in this pathway, and that the inhibition is competitive with respect to the substrate HMG-CoA.The α-methylbutyrate residue of ML-236B appears to play a significant role in the inhibition of HMG-CoA reductase, since both lactone and acid forms of ML-236A, lacking such a residue in their structure, are far less inhibitory than ML-236B analogs.The acid forms of both ML-236A and ML-236B contain a portion having a chem. structure very similar to that of 3-hydroxy-3-methylglutarate.This is compatible with the fact that these compounds are competitive inhibitors of HMG-CoA reductase and further that the acid forms are more potent than the corresponding lactone forms.The results obtained in this study provide good evidence that a specific inhibitor of HMG-CoA reductase is effective in reducing cholesterol synthesis in vivo, and thereby in lowering cholesterol levels in blood.

1988-01-01·The Journal of Antibiotics4区 · 医学

Growth inhibition of yeast by compactin (ML-236B) analogues.

4区 · 医学

Article

作者: Shigeo Murakawa ; Ryutaro Ikeura ; Akira Endo

Of 303 yeast strains tested, 4 strains (Rhodotorula glutinis, Sporobolomyces salmonicolor and Aessosporon salmonicolor [Sporidiobolus johnsonii], and Citeromyces matritensis were sensitive to compactin (I) at 0.1-2.0 μg/mL.The MICs of I as well as the related compounds ML-236A, monacolin K, monacolin L, and monacolin X were determined for R. glutinis H3-9-1 and S. salmonicolor WR 188.Of these compounds I and monacolin K were the most potent, with MICs of 0.1 μg/mL for R. glutinis.S. salmonicolor Was 10-fold more resistant to these compounds than was R. glutinis.Supplementation of 10 mM mevalonate overcame the growth inhibition of the S. salmonicolor by I.In the presence of mevalonate and I, the growth of A. salmonicolor became normal after 10 h.

1986-01-01·The Journal of Antibiotics4区 · 医学

Microbial conversion of compactin (ML-236B) to ML-236A.

4区 · 医学

Article

作者: Endo, Akira ; Yamashita, Haruyuki ; Komagata, Daisuke

Approximately 1,600 fungal strains were tested for ability to convert compactin (ML-236B) to ML-236A and Emericella unguis IFO 8087 was found to be the most active. E. unguis converted ML-236B to ML-236A with a yield of over 90%.

100 项与 ML-236A 相关的药物交易

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