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Physiological relevances of ghrelin synthesis, transport and degradation.

par Delporte, Christine
Référence Physiological relevances of ghrelin synthesis, transport and degradation., Yamada Y. and Takahasgi K., New York, USA, Vol. Ghrelin: production, action mechanisms and physiological effects., Ghrelin: production, action mechanisms and physiological effects.
Publication Publié, 2012

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Résumé :

Ghrelin, previously coined GHS (growth hormone secretagogue), is a 28 amino acid peptide possessing an unusual octanoyl moiety on the serine in position 3. Ghrelin is predominantly produced and secreted into the blood stream by the endocrine X/A like cells of the stomach mucosa in rodents (P/D1 cells in humans). The processing of the 117 amino acids prepro-ghrelin precursor yields ghrelin and another peptide called obestatin. The unusual acylation is catalyzed by ghrelin O-acyl transferase (GOAT), a member of the membrane-bound O-acyl transferase family, adding an octanoyl moiety before the translocation of ghrelin to the Golgi apparatus. Various modified ghrelin peptides have been identified and can be classified into two groups based on their length (28 or 27 amino acids) and/or into four groups based on the presence and nature of the acyl group on the serine in position 3 (non-acylated, octanoylated, decanoylated, decenoylated). Human plasma ghrelin-immunoreactivity consists of more than 90% of des-acyl ghrelin. The shorter half-life of ghrelin compared to des-acyl ghrelin and plasma ghrelin deacylation could account for this observation. Several enzymes have been shown to participate in ghrelin degradation in the stomach and systemically. In the circulation, des-acyl ghrelin is mostly present as a free peptide, while the vast majority of acyl ghrelin is bound to larger molecules such as lipoproteins. Phosphorylation of ghrelin on serine 18 has been reported to affect the amphipathic helix formed by about two third of the C-terminal part of the peptide. However, to date, it is yet unknown if such phosphorylation could occur in cells under specific conditions. The biological activity of ghrelin, via its binding to its growth hormone secretagogue receptor of type A (GHS-R1a), relies on the presence of the voluminous hydrophobic groups on serine 3. The biological activity of the other ghrelin peptides has been pharmacologically evaluated on the GHS-R1a. Biological activities of non-acylated ghrelin have been reported and suggested to occur through an as yet unidentified receptor. Ghrelin synthesis, post-translational modifications, transport, receptor(s) recognition and enzymatic degradation represent important mechanisms that are likely to collectively and co-ordinately modulate the biological activity of ghrelin. © 2012 by Nova Science Publishers, Inc. All rights reserved.