Inhibitory effects of flavonoids on animal fatty acid synthase.
The inhibitory effects of 15 flavonoids on animal fatty acid synthase (FAS, EC 2.3.1.85) were investigated, and 9 of them were found to inhibit FAS with IC(50) (the inhibitor concentration inhibiting 50% of the activity of FAS) values ranging from 2 to 112 microM. A structure-activity relationship study showed that the flavonoids containing two hydroxyl groups in the B ring and 5,7-hydroxyl groups in the A ring in combination with a C-2, 3 double bond were the most inhibitory. Morin (IC(50) = 2.33 +/- 0.09 microM) was further investigated kinetically to detail the inhibitory mechanism. The results showed that morin inhibited the overall reaction of FAS competitively with Ac-CoA, noncompetitively with Mal-CoA and in a mixed manner with NADPH. The study indicated that morin bound reversibly to the beta-ketoacyl synthase domain of FAS to inhibit the elongation of the saturated acyl groups in fatty acids synthesis.
Department of Biology, Graduate School of Chinese Academy of Sciences, P.O. Box 3908, Beijing 100039, PR China.
Bing Hui
BH
Li
Wei Xi
WX
Tian
D000818:Animals; D004372:Ducks; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D005419:Flavonoids; D064429:Fatty Acid Synthases