Novel inhibitors of fatty-acid synthase from green tea (Camellia sinensis Xihu Longjing) with high activity and a new reacting site.
Recent studies have shown that FAS (fatty acid synthase) is a potential therapeutic target of obesity. In the present paper we report that extract of green tea (Camellia sinensis Xihu Longjing) inhibits FAS effectively with an IC50 value of 12.2 microg dry weight/ml. The ability of GTE (green tea extract) to inhibit FAS is more potent than that of two known inhibitors in green tea leaves, EGCG (epigallocatechin gallate) and ECG (epicatechin gallate). We find that (-)-CG (catechin gallate) is a very potent inhibitor of FAS, with an IC50 of 1.5 microg/ml, and may contribute to the high inhibitory effect of GTE on FAS. The inhibitory mechanism of (-)-CG is not mainly involved in its binding to the beta-oxoacyl reductase domain to which both (-)-EGCG and (-)-ECG mainly bind. By analyses of the inhibitory kinetics and the structure of the gallated catechins, we found that the acyl transferase domain may be the main site reacting with (-)-CG, the structure consisting of a B ring, a C ring and a gallate ring, which is possibly essential for its inhibitory efficacy. The polyphenols rather than the alkaloids are the main fractions contributing to the inhibitory effect of GTE on FAS. During separation we also found that the total ability of this portion to inhibit FAS increases by 15-fold, and this may be due to some novel potent inhibitor of FAS other than (-)-CG being formed.
Zhang
Rui
R
Department of Biology, Graduate School of Chinese Academy of Sciences, P.O. Box 3908, Beijing 100049, People's Republic of China.
Xiao
Wenping
W
Wang
Xuan
X
Wu
Xiaodong
X
Tian
Weixi
W
D028241:Camellia sinensis / Q000737:chemistry*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors*; D005419:Flavonoids / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D009765:Obesity; D010636:Phenols / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D059808:Polyphenols; D013662:Tea
D004791:Enzyme Inhibitors; D005419:Flavonoids; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; D013662:Tea; C417939:catechin gallate; D002392:Catechin; C062669:epicatechin gallate; C045651:epigallocatechin gallate; D064429:Fatty Acid Synthases