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Novel inhibitors of fatty‐acid synthase from green tea ( Camellia sinensis Xihu Longjing) with high activity and a new reacting site
Author(s) -
Zhang Rui,
Xiao Wenping,
Wang Xuan,
Wu Xiaodong,
Tian Weixi
Publication year - 2006
Publication title -
biotechnology and applied biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 70
eISSN - 1470-8744
pISSN - 0885-4513
DOI - 10.1042/ba20050064
Subject(s) - fatty acid synthase , epigallocatechin gallate , catechin , camellia sinensis , epicatechin gallate , ic50 , biochemistry , green tea extract , chemistry , polyphenol , enzyme inhibitor , enzyme , stereochemistry , biology , green tea , food science , in vitro , antioxidant , botany
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 IC 50 value of 12.2 μg 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 IC 50 of 1.5 μg/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 β‐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.