(−)‐Epigallocatechin‐3‐gallate inhibits human angiotensin‐converting enzyme activity through an autoxidation‐dependent mechanism. Issue 9 (23rd May 2017)

• Record Type: Journal Article
• Authors: Liu, Zhe; Nakashima, Sayaka; Nakamura, Toshiyuki; Munemasa, Shintaro; Murata, Yoshiyuki; Nakamura, Yoshimasa
• Is Part Of: Journal of biochemical and molecular toxicology. Volume 31:Issue 9(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-05-23
• Subjects: (−)‐epigallocatechin‐3‐gallate -- angiotensin‐converting enzyme -- covalent modification -- non‐competitive inhibition; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Toxicology -- Periodicals; 574
• DOI: 10.1002/jbt.21932
• Languages: English
• ISSNs: 1095-6670

Abstract

Abstract: 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.