Synthesis, secretion, and deacylation of Ghrelin

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.

促胃液素是一种由28个氨基酸残基组成的肽类激素，其在成熟肽的丝氨酸-3位发生酰化。促胃液素在多个组织中合成：胃黏膜的X/A样细胞（促胃液素的主要来源）、下丘脑、垂体、肾上腺、甲状腺、乳腺、卵巢、胎盘、输卵管、睾丸、前列腺、肝脏、胆囊、胰腺、脂肪组织、人类淋巴细胞、脾脏、肾脏、肺、骨骼肌、心肌、静脉和皮肤。促胃液素与存在于下丘脑、垂体及其他组织的GHS-R1a受体结合，其结合可引起食欲刺激和生长激素的释放。循环中促胃液素的水平在禁食期间上升，在餐前达到峰值，并根据摄入的热量下降。<br>前促胃液素被切割生成促胃液素，随后由促胃液素O-酰基转移酶酰化，生成辛酰促胃液素和癸酰促胃液素。只有辛酰促胃液素能够结合并激活GHS-R1a受体。未酰化的促胃液素（去酰促胃液素）也存在于血浆中，但其功能尚存争议。<br>酰基促胃液素由前激素转换酶1/3切割，生成成熟的酰基促胃液素和C-促胃液素。胰岛素、生长激素（生长激素素）、脂联素、葡萄糖、胰高血糖素和脂肪酸会抑制促胃液素的分泌。胰岛素样生长因子-1和毒蕈碱激动剂则会刺激促胃液素的分泌。<br>在血液循环中，酰基促胃液素由丁酰胆碱酯酶和血小板活化因子乙酰水解酶脱酰化。其他酶也可能脱酰酰基促胃液素。