Identification and characterisation of the currently unknown gene for human carnosine synthetase (EC 6.3.2.11) upon purification of the homologous enzyme from Gallus gallus

从原鸡中纯化同源酶后，对目前未知的人肌肽合成酶 (EC 6.3.2.11) 基因进行鉴定和表征

• 批准号: 48595870
• 负责人: Professor Dr. Matthias Mack
• 金额: --
• 依托单位: Dietmar-Hopp-Stoffwechselzentrum
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2012-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/48595870?language=en
• 关键词: Identification; characterisation; currently; unknown; gene

The currently unknown gene for human carnosine synthetase (EC 6.3.2.11) will be identified in order to facilitate studies on carnosine metabolism in the development of diabetic nephropathy. Furthermore, the physiological role of the dipeptide carnosine (β-alanyl-L-histidine), which is present in high concentrations (up to 20 mM) in human skeletal muscle, is still unclear. The biochemical characterization of the carnosine producing enzyme should contribute to the general understanding of carnosine function. We recently found that a variant of the carnosin-degrading enzyme serum carnosinase is associated with protection from diabetic nephrophathy. The biological basis of this effect is unclear. Carnosine synthetase has been purified earlier from Gallus gallus but sequence information was not produced. The enzyme was reported to be difficult to handle. With new chromatographic methods isolation of the protein should be straightforward. Following purification, sequence information will be generated and the homologous mammalian genes will be identified in silico. The expression level will be followed in various tissues. The relevance of possible functional variants of carnosine synthetase in the pathogenesis of diabetic nephropathy will be examined through association studies in patients and controls.

目前未知的人肌肽合成酶基因（EC 6.3.2.11）将被鉴定，以促进糖尿病肾病发展过程中肌肽代谢的研究。此外，人类骨骼肌中高浓度（高达 20 mM）的二肽肌肽（β-丙氨酰-L-组氨酸）的生理作用仍不清楚。肌肽产生酶的生化特征应有助于对肌肽功能的一般理解。我们最近发现肌肽降解酶血清肌肽酶的一种变体与预防糖尿病肾病有关。这种效应的生物学基础尚不清楚。肌肽合成酶较早已从鸡内纯化出来，但未产生序列信息。据报道这种酶很难处理。使用新的色谱方法，蛋白质的分离应该很简单。纯化后，将生成序列信息，并在计算机中鉴定同源哺乳动物基因。将跟踪各种组织中的表达水平。将通过患者和对照的关联研究来检查肌肽合成酶可能的功能变异在糖尿病肾病发病机制中的相关性。