合成NAD的新途径.docVIP

合成NAD的新途径烟酰胺腺嘌呤二核苷酸（nicotinamide adenine dinucleotide，NAD）是有机体必不可少的多功能小分子，主要作为氧化还原酶（oxidoreductase）的重要辅酶和核糖二磷酸腺甙（ADPribosyl）的来源。正是利用了这种重要性，以tiazofurin 和benzamide riboside为代表的抗癌药物通过转变成毒性的NAD类似物而发挥效用。最近还发现，在实验系统中许多能够延长生命的蛋白都是NAD依赖性的。NAD的合成前体一直认为只有烟酸（nicotinic acid）和烟碱（nicotinamide）。然而最近，一条新的代谢途径被发现；并且，这个途径还可能有重要的作用。 在最近一期的《细胞》杂志上发表了Dartmouth Medical School的Pawel Bieganowski 和Charles Brenner的研究结果，揭示了在酵母系统中，烟碱核糖甙（nicotinamide riboside）可以作为NAD的新前体，而且，人和酵母的烟碱核糖甙激酶（nicotinamide riboside kinases）都可以在这条代谢途径中发挥重要作用。 一直依赖都认为，NAD合成酶（NAD+ Synthetase）是NAD合成所必需的，然而实验表明，烟碱核糖甙可以形成NAD合成酶非依赖性的酵母生长。随后，研究者又找到了对这一途径起重要最用的烟碱核糖甙激酶；而且发现， 和烟碱核糖甙类似的tiazofurin 和benzamide riboside似乎也是通过这个途径转变成毒性的NAD类似物。 在奶清中烟碱核糖甙的发现，也提示烟碱核糖甙可能也有助于人体中NAD水平的上升。另一方面，通过对烟碱核糖甙激酶的检测，也许可以揭示tiazofurin 和benzamide riboside类的药物，对癌症病人的效果为什么大相径庭。Novel Vitamin Discovery Offers Clues For Cancer Chemotherapy And Lipid Disorders ScienceDaily (May 14, 2004) — HANOVER, NH - Dartmouth Medical School cancer researchers, in a fusion of biochemistry and genetics, have discovered a new vitamin in a molecular pathway central to such vital processes as gene regulation, metabolism and aging. And, they found that milk contains this nutrient The work, published in the May 14 issue of Cell, defines another metabolic route to a compound called NAD and suggests that therapeutic approaches for cancer or heart disease may depend on the enzymes discovered. NAD (nicotinamide adenine dinucleotide) is one of the most well-known small molecules in the cell, said Dr. Charles Brenner, associate professor of genetics and of biochemistry, author of the study with Dr. Pawel Bieganowski, a postdoctoral fellow. It is essential for life in all organisms, from bacteria to humans, and very versatile, working both as a partner that helps enzymes and as an ingredient that other enzymes consume. NAD is a co-enzyme for hundreds of cellular enzymes. Niacin, or vitamin B3, a mixture of the NAD precursors nicotinic acid and nicotinamide, which were discovere