赛尔图因4是一种可调节酸盐脱酶复合体活性的胺酶
Rommel A Mathias1, Todd M Greco2, Adam Oberstein2
1Department of Molecular Biology, Princeton University, Princeton, NJ, 08544, USA; Department of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, 3086, Australia.
Cell
|December 20, 2014
概括
SIRT4是一种脂胺酶,而不是脱乙酶,通过去除脂胺辅因子来调节酸盐脱酶复合体 (PDH). 这一发现显示SIRT4的存在.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 代谢调节 代谢调节 代谢调节
背景情况:
- 赛尔图因 (SIRT) 是NAD+依赖的酶,参与各种细胞过程,包括衰老和新陈代谢.
- 线粒体sirtuins SIRT4和SIRT5表现出有限的脱乙酶活性,而SIRT4的催化功能在很大程度上仍未被描述.
- 酸盐脱酶复合体 (PDH) 是一个关键的代谢酶复合体,调节酸盐转化为乙-CoA.
研究的目的:
- 阐明线粒体Sirtuin 4 (SIRT4) 的催化活性和功能.
- 调查SIRT4在调节酸盐脱酶复合体 (PDH) 中的作用.
- 将SIRT4描述为代谢障碍的潜在治疗标.
主要方法:
- 酶分析测定SIRT4在各种基质上的催化活性,包括酸和酸.
- 对PDH复杂组件的生物化学分析,特别是二脂氨酸乙烯转移酶 (DLAT).
- 在小鼠肝脏中进行细胞和体内研究,以评估SIRT4对PDH活性和脂解的生理影响.
主要成果:
- SIRT4作为胺酶起作用,有效地从氨酸残留物中化胺辅因子.
- SIRT4的胺酶活性明显高于其脱乙酶活性.
- SIRT4直接准PDH复合物的组成部分DLAT,导致PDH活性降低.
- 在细胞模型和小鼠肝脏中观察到SIRT4介导的PDH活性抑制.
- 谷氨胺诱导的代谢流激活SIRT4的胺酶功能,抑制PDH.
结论:
- SIRT4是一种线粒体胺酶,通过从DLAT分离胺辅因子来调节PDH活性.
- 这种胺酶活性代表了SIRT4的主要催化功能,与其已知的脱乙酶功能不同.
- SIRT4作为细胞代谢的关键调节者,特别是在对像谷氨酸刺激这样的代谢线索的反应中发挥作用.
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