Identification of the Acyltransferase That Octanoylates Ghrelin, an Appetite-Stimulating Peptide Hormone

Cell. 2008 Feb 8;132(3):387-96. doi: 10.1016/j.cell.2008.01.017.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / genetics*
  • Acyltransferases / metabolism*
  • Amino Acid Sequence
  • Animals
  • Caprylates / metabolism*
  • Cloning, Molecular
  • Gene Expression Profiling
  • Genome
  • Ghrelin / metabolism*
  • Humans
  • Membrane Proteins
  • Mice
  • Molecular Sequence Data
  • Organ Specificity
  • Protein Precursors / genetics
  • Protein Precursors / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Sequence Alignment

Substances

  • Caprylates
  • Ghrelin
  • Membrane Proteins
  • Protein Precursors
  • RNA, Messenger
  • Acyltransferases
  • Mboat4 protein, mouse
  • octanoic acid