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 discovered in 1938, prevents pellagra and can help control cholesterol. A class of anti-cancer drugs including tiazofurin and benzamide riboside is converted to toxic NAD analogs. And, more recently, proteins dependent on NAD have been shown to prolong life in experimental systems.
Brenner's laboratory at the Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center was studying an enzyme involved in NAD synthesis that was similar to an enzyme implicated in cancer development. Their explorations revealed a novel twist. In yeast without the enzyme, every known NAD biosynthetic pathway was shut down, so in theory, the cells should die; no vitamins or supplements were known to keep the cells alive. However, the researchers discovered that another NAD precursor, nicotinamide riboside, thought to be a vitamin form of NAD only in certain bacteria, served as a vitamin in yea
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Contact: Andrew Nordhoff
W.Andrew.Nordhoff@Dartmouth.edu
603-650-1492
Dartmouth Medical School
13-May-2004