Satou Motoyasu, Sugimoto Hiroyuki
Department of Biochemistry, Dokkyo Medical University School of Medicine, Mibu, Tochigi, Japan.
Methods Enzymol. 2012;514:165-79. doi: 10.1016/B978-0-12-381272-8.00011-8.
Like other posttranslational modifications, fatty acid modification of amino acid residues in peptide chains is a critical determinant of their functional properties. A unique feature of ghrelin is the attachment of an acyl moiety at the third serine residue. Ghrelin is a hormone present in the circulation with roles in the release of growth hormone, control of behaviors related to appetite, and diverse cellular functions. Although lipid modification of ghrelin is essential for its binding to the ghrelin receptor, several lines of evidence suggest that deacylated ghrelin has physiological activity or activities similar to and distinct from the activities of the acylated form. Therefore, the understanding of deacylating process of ghrelin in vivo is key to accepting the physiological importance of ghrelin. In this review, we summarize results and methodology relevant to our recent efforts to determine the molecular mechanisms involved in ghrelin processing, including (1) immunological and mass spectrometry-based detection of ghrelin, (2) quantification of ghrelin deacylase activity, and (3) characterization of ghrelin deacylation enzymes isolated from biological fluids and using heterologous expression systems.
与其他翻译后修饰一样，肽链中氨基酸残基的脂肪酸修饰是其功能特性的关键决定因素。胃饥饿素的一个独特特征是在第三个丝氨酸残基处连接一个酰基部分。胃饥饿素是一种存在于循环系统中的激素，在生长激素释放、控制与食欲相关的行为以及多种细胞功能中发挥作用。尽管胃饥饿素的脂质修饰对于其与胃饥饿素受体的结合至关重要，但有几条证据表明，去酰基化的胃饥饿素具有与酰化形式相似且不同的生理活性。因此，了解体内胃饥饿素的去酰基化过程是认识胃饥饿素生理重要性的关键。在这篇综述中，我们总结了与我们最近确定胃饥饿素加工过程中涉及的分子机制的努力相关的结果和方法，包括（1）基于免疫和质谱的胃饥饿素检测，（2）胃饥饿素去酰基酶活性的定量，以及（3）从生物流体中分离并使用异源表达系统对胃饥饿素去酰基化酶的表征。
