Ghrelin is a 28-amino acid peptide hormone that has been shown to stimulate food intake in both rats and humans. It is synthesized in zymogenic form as prepro-ghrelin and processed initially to pro-ghrelin and then to the active form ghrelin (Fig. 1). Octanoylation at ghrelin serine-3 is required for activity. This study identifies and characterizes the enzyme responsible for attaching octanoate to ghrelin. Ghrelin O-acyltransferase (GOAT) belongs to a family of membrane-bound O-acyltransferases found in mice that attach fatty acids to membrane-associated hydroxyl receptors (Fig. 2). Coexpression of GOAT with prepro-ghrelin in three endocrine cell lines resulted in the production of acylated ghrelin. Mutation of ghrelin Ser 3 to Ala prevented acylation by GOAT. The probable catalytic amino acid residues within GOAT are Asp 307 and His 338, because substitution of either of these residues with Ala abolished the ability of GOAT to (Figure Presented) acylate ghrelin. Labeling studies suggested that GOAT octanoylates proghrelin prior to its cleavage to ghrelin. GOAT was also found to have the same tissue expression pattern as ghrelin, further supporting a probable regulatory role in ghrelin's activity.
|Original language||English (US)|
|Number of pages||2|
|Publication status||Published - Mar 2008|
ASJC Scopus subject areas
- Molecular Biology