(-)-Epigallocatechin-3-gallate inhibits human angiotensin-converting enzyme activity through an autoxidation-dependent mechanism.

We investigated the molecular mechanisms involved in the angiotensin-converting enzyme (ACE) inhibition by (-)-epigallocatechin-3-gallate (EGCg), a major tea catechin. EGCg inhibited both the ACE activity in the lysate of human colorectal cancer cells and human recombinant ACE (rh-ACE) in a dose-dependent manner. Co-incubation with zinc sulfate showed no influence on the rh-ACE inhibition by EGCg, whereas it completely counteracted the inhibitory effect of ethylenediaminetetraacetic acid, a chelating-type ACE inhibitor. Although hydrogen peroxide was produced by the autoxidation of EGCg, hydrogen peroxide itself had little effect on the ACE activity. Conversely, the co-incubation of EGCg with borate or ascorbic acid significantly diminished the EGCg inhibition. A redox-cycling staining experiment revealed that rh-ACE was covalently modified by EGCg. A Lineweaver-Burk plot analysis indicated that EGCg inhibited the ACE activity in a non-competitive manner. These results suggested that EGCg might allosterically inhibit the ACE activity through oxidative conversion into an electrophilic quinone.