title: Understanding the functional significance of ghrelin processing and degradation.
abstract: Post-translational modification, cleavage and processing of circulating hormones are common themes in the control of hormone activities. Full-length ghrelin is a 28 amino acid protein that exists in several modified and processed forms, including addition of an acyl moiety at the third serine of the N-terminus. When modified with octanoic acid, the first five N-terminal residues of ghrelin can modulate a signaling pathway via the ghrelin receptor GHSR1a. Although modification via a lipid moiety is essential for binding and activation of GHSR1a by ghrelin, many reports suggest that a desacyl form of ghrelin exists and has synergistic, opposing and distinct properties as compared to the acyl form. Therefore, it is important to clarify the physiological relevance of ghrelin derivatives. Based on lines of evidence from various studies, we propose that a larger proportion of secreted ghrelin is present in the deacylated form and furthermore, that circulating acyl and desacyl forms of ghrelin may be hydrolyzed to form short peptide fragments. Here, we summarize the results of studies aimed at understanding ghrelin processing and its implications for physiological function, as well as our recent findings regarding enzymes in the blood capable of generating processed forms of ghrelin.
authors.affiliation: Departments of Biochemistry, Dokkyo Medical University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan.
authors.forename: Motoyasu
authors.initials: M
authors.lastname: Satou
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ando
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sugimoto
mesh_terms: D000215:Acylation; D000217:Acyltransferases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002210:Caprylates / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D054439:Ghrelin / Q000097:blood* / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008245:Lysophospholipase / Q000378:metabolism; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000097:blood* / Q000737:chemistry / Q000235:genetics; D020033:Protein Isoforms / Q000097:blood* / Q000737:chemistry / Q000235:genetics; D059748:Proteolysis; D054440:Receptors, Ghrelin / Q000378:metabolism*; D012694:Serine / Q000737:chemistry / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013869:Thiolester Hydrolases / Q000378:metabolism
chemical_list: D002210:Caprylates; D054439:Ghrelin; D010446:Peptide Fragments; D020033:Protein Isoforms; D054440:Receptors, Ghrelin; D012694:Serine; D000217:Acyltransferases; C542776:MBOAT4 protein, human; D008245:Lysophospholipase; C402226:LYPLA1 protein, human; D013869:Thiolester Hydrolases; C031492:octanoic acid