The galloyl moiety of green tea catechins is the critical structural feature to inhibit fatty-acid synthase

Xuan Wang, Ke Sheng Song, Qing Xiang Guo, Wei Xi Tian

Research output: Contribution to journalArticle

102 Scopus citations

Abstract

It has been reported that inhibition of fatty-acid synthase (FAS) is selectively cytotoxic to human cancer cells. Considerable interest has developed in identifying novel inhibitors of this enzyme complex. Our previous work showed that green tea (-)-epigallocatechin gallate can inhibit FAS in vitro. To elucidate the structure-activity relationship of the inhibitory effects of tea polyphenols, we investigated the inhibition kinetics of the major catechins and analogues. Ungallated catechins from green tea do not show obvious inhibition compared with gallated catechins. Another gallated catechin, (-)-epicatechin gallate, was also found as a potent inhibitor of FAS and its inhibition characteristics are similar to (-)-epigallocatechin gallate. Furthermore, the analogues of galloyl moiety without the catechin skeleton such as propyl gallate also showed obvious slow-binding inhibition, whereas the green tea ungallated catechin not. Atomic orbital energy analyses suggest that the positive charge is more distinctly distributed on the carbon atom of ester bond of galloyl moiety of gallate catechins, and that gallated forms are more susceptible for a nucleophilic attack than other catechins. Here we identify the galloyl moiety of green tea catechins as critical in the inactivation of the ketoacyl reductase activity of FAS for the first time.

Original languageEnglish (US)
Pages (from-to)2039-2047
Number of pages9
JournalBiochemical Pharmacology
Volume66
Issue number10
DOIs
StatePublished - Nov 15 2003
Externally publishedYes

Keywords

  • Fatty-acid synthase
  • Gallated catechins
  • Galloyl moiety
  • Inhibition
  • Steady-state kinetics

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Fingerprint Dive into the research topics of 'The galloyl moiety of green tea catechins is the critical structural feature to inhibit fatty-acid synthase'. Together they form a unique fingerprint.

  • Cite this