Author(s): Yang J, Brown MS, Liang G, Grishin NV, Goldstein JL
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Abstract Ghrelin is a 28 amino acid, appetite-stimulating peptide hormone secreted by the food-deprived stomach. Serine-3 of ghrelin is acylated with an eight-carbon fatty acid, octanoate, which is required for its endocrine actions. Here, we identify GOAT (Ghrelin O-Acyltransferase), a polytopic membrane-bound enzyme that attaches octanoate to serine-3 of ghrelin. Analysis of the mouse genome revealed that GOAT belongs to a family of 16 hydrophobic membrane-bound acyltransferases that includes Porcupine, which attaches long-chain fatty acids to Wnt proteins. GOAT is the only member of this family that octanoylates ghrelin when coexpressed in cultured endocrine cell lines with prepro-ghrelin. GOAT activity requires catalytic asparagine and histidine residues that are conserved in this family. Consistent with its function, GOAT mRNA is largely restricted to stomach and intestine, the major ghrelin-secreting tissues. Identification of GOAT will facilitate the search for inhibitors that reduce appetite and diminish obesity in humans.
This article was published in Cell
and referenced in Journal of Diabetes & Metabolism