Nakagawa Takashi, Guarente Leonard
Paul F. Glenn Laboratory for the Science of Aging and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Aging (Albany NY). 2009 Jun 29;1(6):578-81. doi: 10.18632/aging.100062.
Mammalian sirtuins have diverse roles in aging, metabolism and disease. Recently we reported a new function for SIRT5 in urea cycle regulation. Our study uncovered that SIRT5 localized to mitochondria matrix and deacetylates carbamoyl phosphate synthetase 1 (CPS1), an enzyme which is the first and rate-limiting step of urea cycle. Deacetylation of CPS1 by SIRT5 resulted in activation of CPS1 enzymatic activity. Indeed, SIRT5-deficient mice failed to up-regulate CPS1 activity and showed hyper ammonemia during fasting. Similar effects are also observed on high protein diet or calorie restriction. These data indicate SIRT5 also has an emerging role in the metabolic adaptation to fasting, high protein diet and calorie restriction.
哺乳动物的沉默调节蛋白在衰老、新陈代谢和疾病中具有多种作用。最近我们报道了SIRT5在尿素循环调节中的新功能。我们的研究发现SIRT5定位于线粒体基质，并使氨甲酰磷酸合成酶1（CPS1）去乙酰化，CPS1是尿素循环的第一步也是限速步骤的一种酶。SIRT5对CPS1的去乙酰化导致CPS1酶活性的激活。事实上，缺乏SIRT5的小鼠在禁食期间未能上调CPS1活性，并表现出高氨血症。在高蛋白饮食或热量限制情况下也观察到类似的效果。这些数据表明SIRT5在对禁食、高蛋白饮食和热量限制的代谢适应中也发挥着新的作用。
