Biochemistry of ghrelin precursor peptides.
Since its discovery in 1999, the stomach-derived hormone ghrelin has been studied intensively. Proghrelin is 94 amino acids long in mammals and this undergoes proteolytic processing to produce ghrelin [residues 1-28 of proghrelin(1-94)] and the C-terminal peptide C-ghrelin, which likely contains the entire 66 amino acids of the prohormone C-terminus. The accumulating data identifies ghrelin as having important roles in growth hormone (GH) release, appetite, metabolism, energy balance, cardiovascular function, reproduction, and bone growth. The most striking feature of ghrelin is that it can be acylated at its third amino acid residue (usually Ser), usually in the form of n-octanoyl group (C8:0). Approximately 10-20% of circulating ghrelin is acylated and this feature confers its GH releasing ability, mediated by the GH secretagogue receptor (GHSR). In contrast, the remaining 80-90% of circulating ghrelin is desacylated. Desacyl ghrelin was initially thought to be inactive, but recent in vivo and in vitro evidences have identified biological actions for this peptide, independent of GHSR. Whether C-ghrelin has bioactivity remains to be determined, but it is known that plasma concentrations of this peptide respond to endocrine and metabolic manipulations in the same fashion as ghrelin itself. A third putative proghrelin peptide, termed "obestatin" has been mooted, but confirmatory biochemical and functional evidences supporting the existence of this peptide have not been forthcoming, suggesting it to be a biochemical miscalculation. This chapter will address biochemical aspects of proghrelin peptides and point to potential avenues for future work.
Pemberton
Chris J
CJ
Christchurch Cardioendocrine Research Group, Department of Medicine, Christchurch School of Medicine and Health Sciences, University of Otago, Christchurch, New Zealand.
Richards
A Mark
AM
D000595:Amino Acid Sequence; D000818:Animals; D054439:Ghrelin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational
D054439:Ghrelin; D011498:Protein Precursors