PathwayStep4069 PathwayStep4072 PathwayStep4073 PathwayStep4070 PathwayStep4071 PathwayStep4074 PathwayStep4075 Cleavage of the Signal Peptide of Preproghrelin Octanoylation of Proghrelin by Ghrelin O-acyltransferase Secretion of Acyl Ghrelin and C-Ghrelin Cleavage of Acyl Proghrelin by Prohormone Convertase 1/3 Deacylation of Acyl Ghrelin Decanoylation of Proghrelin by Ghrelin O-acyltransferase Synthesis of Preproghrelin Synthesis, Secretion, and Deacylation of Ghrelin Authored: May, B, 2009-06-10 Edited: May, B, 2009-06-10 Ghrelin is a peptide hormone of 28 amino acid residues which is acylated at the serine-3 of the mature peptide. Ghrelin is synthesized in several tissues: X/A-like cells of the gastric mucosa (the major source of ghrelin), hypothalamus, pituitary, adrenal gland, thyroid, breast, ovary, placenta, fallopian tube, testis, prostate, liver, gall bladder, pancreas, fat tissue, human lymphocytes, spleen, kidney, lung, skeletal muscle, myocardium, vein and skin. Ghrelin binds the GHS-R1a receptor present in hypothalamus pituitary, and other tissues. Binding causes appetite stimulation and release of growth hormone. Levels of circulating ghrelin rise during fasting, peak before a meal, and fall according to the calories ingested.<br>Preproghrelin is cleaved to yield proghrelin which is then acylated by ghrelin O-acyltransferase to yield octanoyl ghrelin and decanoyl ghrelin. Only octanoyl ghrelin is able to bind and activate the GHS-R1a receptor. Unacylated ghrelin (des-acyl ghrelin) is also present in plasma but its function is controversial.<br>Acyl proghrelin is cleaved by prohormone convertase 1/3 to yield the mature acyl ghrelin and C-ghrelin. Secretion of ghrelin is inhibited by insulin, growth hormone (somatotropin), leptin, glucose, glucagon, and fatty acids. Secretion is stimulated by insulin-like growth factor-1 and muscarinic agonists.<br>In the bloodstream acyl ghrelin is deacylated by butyrylcholinesterase and platelet-activating factor acetylhydrolase. Other enzymes may also deacylate acyl ghrelin. Pubmed18396350 Pubmed19280057 Reactome Database ID Release 43422085 Reactome, http://www.reactome.org ReactomeREACT_19189 Reviewed: Zhang, Weizhen, 2009-08-29