My watch list
my.bionity.com  
Login  

Cerulenin



Cerulenin is an antifungal antibiotic that inhibits sterol and fatty acid biosynthesis. In fatty acid synthesis, it has been reported to bind in equimolar ratio to b-keto-acyl-ACP synthase, one of the seven moieties of fatty acid synthase, blocking the interaction of malonyl-CoA. It also has the related activity of stimulating fatty acid oxidation through the activation of CPT1, another enzyme normally inhibited by malonyl-CoA. Inhibition involves covalent thioacylation that permanently inactivates the enzymes.[1] These two behaviors may increase the availability of energy in the form of ATP, perhaps sensed by AMPK, in the hypothalamus.[2] In sterol synthesis, cerulenin inhibits HMG-CoA synthetase activity.[3] Cerulenin causes a dose-dependent decrease in HER2/neu protein levels in breast cancer cells, from 14% at 1.25 to 78% at 10 milligrams per liter, and targeting of fatty acid synthase by related drugs has been suggested as a possible treatment. [4] Antiproliferative and pro-apoptotic effects have been shown in colon cells as well.[5] At an intraperitoneal dose of 30 milligrams per kilogram, it has been shown to inhibit feeding and induce dramatic weight loss in mice by a mechanism similar to, but independent or downstream of, leptin signaling.[6] It is found naturally in the industrial strain 'Cephalosporium caerulens' (Sarocladium oryzae, the sheath rot pathogen of rice).

References

  1. ^ Straub SG, Yajima H, Komatsu M, Aizawa T, Sharp GW. The effects of cerulenin, an inhibitor of protein acylation, on the two phases of glucose-stimulated insulin secretion. Diabetes. 2002 Feb;51 Suppl 1:S91-5.
  2. ^ reviewed in PMID 17021367
  3. ^ PMID 4157441
  4. ^ PMID 15235125
  5. ^ Huang P, Zhu S, Lu S, Dai Z, Jin Y.] An experimental study on cerulenin induced apoptosis of human colonic cancer cells. PMID 11866903 Zhonghua Bing Li Xue Za Zhi. 2000 Apr;29(2):115-8.
  6. ^ PMID 12028418
 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Cerulenin". A list of authors is available in Wikipedia.
Your browser is not current. Microsoft Internet Explorer 6.0 does not support some functions on Chemie.DE