Enzymatic processing of ghrelin precursor

Abstract

Ghrelin, an orexigenic peptide hormone from stomach, generally contains an acyl modi fi cation at the third serine residue. The serine is modi fi ed with a medium-chain fatty acid, typically n -octanoic acid. Importantly, this modi fi cation is essential for the biological activity of ghrelin. Conservation of the sequence and the required acyl modi fi cation at the third residue suggest that ghrelin undergoes a precise series of processing steps. The enzyme that catalyzes the transfer of the acyl moiety to ghrelin was identi fi ed as ghrelin O -acyltransferase (GOAT). GOAT is a membrane-bound acyltransferase, speci fi c for the acyl-modi fi cation of ghrelin. Interestingly, most ghrelin in the stomach is modi fi ed by n -octanoic acid; however, GOAT prefers to use n -hexanoic acid as the acyl donor rather than n -octanoic acid. The enzymes responsible for ghrelin processing, such as protease cleavage, acyl modi fi cation, and deacylation, have been identi fi ed and characterized in vivo and in vitro. The ghrelin-processing enzymes may be good targets for drug development to treat metabolic diseases and eating disorders.