The regulation of nicotinamide adenine dinucleotide biosynthesis by Nampt/PBEF/visfatin in mammals
The regulation of nicotinamide adenine dinucleotide biosynthesis by Nampt/PBEF/visfatin in mammals
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DOI：
10.1097/mog.0b013e32801b3c8f
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发表时间：
2007-03-01
影响因子：
2.5
通讯作者：
Imai, Shin-ichiro
中科院分区：
文献类型：
--
作者：
Revollo, Javier R.;Grimm, Andrew A.;Imai, Shin-ichiro
烟酰胺腺嘌呤二核苷酸（NAD）是细胞氧化还原反应中的一种典型辅酶。近年来，NAD生物化学在哺乳动物中也涉及到更广泛的生物学功能，但对NAD生物合成的调控研究甚少。近年来NAD生物化学领域的研究进展使人们对NAD的生物合成途径及其在代谢中的生理作用产生了新的兴趣。本文综述了NAD生物合成途径的最新进展，重点介绍了NAD生物合成的关键酶之一，即烟酰胺磷酸核糖基转移酶。哺乳动物主要使用烟酰胺而不是烟酸作为NAD生物合成的前体。烟酰胺磷酸核糖基转移酶（Nampt）是哺乳动物NAD生物合成途径中将烟酰胺转化为烟酰胺单核苷酸的限速酶。同样的蛋白质也被确定为细胞因子（前b细胞集落增强因子或PBEF）或胰岛素模拟激素（visfatin）。我们认为Nampt/PBEF/visfatin的多重作用可能完全由其作为细胞内和细胞外NAD生物合成酶的作用来解释。我们还提出了Namp/PBEF/visfatin介导的全身NAD生物合成的新模型及其可能的生理意义。我们的模型为开发针对代谢并发症（如肥胖和糖尿病）的预防/治疗干预措施提供了重要的见解。
Purpose of review Nicotinamide adenine dinucleotide (NAD) is a classic coenzyme in cellular redox reactions. Recently, NAD biochemistry has also been implicated in a broader range of biological functions in mammals, but the regulation of NAD biosynthesis has been poorly investigated. Recent progress in the field of NAD biochemistry has fueled new interest in the NAD biosynthetic pathways from its precursors and their physiological roles in metabolism. This review summarizes the latest knowledge on the NAD biosynthetic pathways and focuses on one of the key NAD biosynthetic enzymes, namely, nicotinamide phosphoribosyltransferase.Recent findings Mammals predominantly use nicotinamide rather than nicotinic acid as a precursor for NAD biosynthesis. Nicotinamide phosphoribosyltransferase (Nampt) is the rate-limiting enzyme that converts nicotinamide to nicotinamide mononucleotide in the NAD biosynthetic pathway from nicotinamide in mammals. The same protein has also been identified as a cytokine (pre-B-cell colony-enhancing factor or PBEF) or an insulin-mimetic hormone (visfatin).Summary We propose that the presumed multiple effects of Nampt/PBEF/visfatin may be entirely explained by its role as an intra and extracellular NAD biosynthetic enzyme. We also propose a new model of Namp/PBEF/visfatin-mediated systemic NAD biosynthesis and its possible physiological significance. Our model provides an important insight into developing preventive/therapeutic interventions for metabolic complications, such as obesity and diabetes.