Green tea epigallocatechin gallate: A natural inhibitor of fatty-acid synthase

Xuan Wang, Weixi Tian

Research output: Contribution to journalArticle

150 Scopus citations

Abstract

We discover that epigallocatechin gallate (EGCG) from green tea is an inhibitor of fatty-acid synthase (FAS) from chicken liver. Its inhibition of FAS is composed of reversible fast-binding inhibition, through which 52 μM EGCG can inhibit 50% of the activity of FAS, and irreversible slow-binding inactivation following saturation kinetics with the dissociation constant of 0.352 mM and limiting rate constant of 0.0168 min-1. The marked inhibition of ketoacyl reduction shows that the inhibition is related to β-ketoacyl reductase of FAS. The observable protection of NADPH and competitive inhibition of NADPH for ketoacyl reduction indicate that EGCG may compete with NADPH for the same binding site. The synthetic inhibitor C75 does not show obvious fast-binding inhibition, but does exhibit irreversible slow-binding biphasic inactivation, which is demonstrated to be a second-order reaction. That the inactivation by C75 is protected by malonyl-CoA indicates C75 is similar to cerulenin in being a covalent inactivator of the β-ketoacyl synthase.

Original languageEnglish (US)
Pages (from-to)1200-1206
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume288
Issue number5
DOIs
StatePublished - Nov 16 2001
Externally publishedYes

Keywords

  • C75
  • Epigallocatechin gallate (EGCG)
  • Fatty-acid synthase (FAS)
  • Inhibition kinetics
  • Inhibitor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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