Enzymatic Processing of Ghrelin Precursor

Abstract

Ghrelin, an orexigenic peptide hormone from stomach, generally contains an acyl modification at the third serine residue. The serine is modified with a medium-chain fatty acid, typically n-octanoic acid. Importantly, this modification is essential for the biological activity of ghrelin. Conservation of the sequence and the required acyl modification 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 identified as ghrelin O-acyltransferase (GOAT). GOAT is a membrane-bound acyltransferase, specific for the acyl-modification of ghrelin. Interestingly, most ghrelin in the stomach is modified 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 modification, and deacylation, have been identified 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.KeywordsAcyl DonorGhrelin AcylationProcessing ProteaseGhrelin ActivityGhrelin PeptideThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.