Biological Oxidation-Reduction Reactions:- Dietary Deficiency of Niacin, the Vitamin Form of NAD and NADP, Causes Pellagra
The pyridine-like rings of NAD and NADP are de rived from the vitamin niacin (nicotinic acid; Fig. 13–17), which is synthesized from tryptophan. Humans generally cannot synthesize niacin in sufficient quantities, and this is especially so for those with diets low in tryptophan (maize, for example, has a low tryptophan content). Niacin deficiency, which affects all the NAD(P)-dependent dehydrogenases, causes the serious human disease pellagra (Italian for “rough skin”) and a related disease in dogs, blacktongue. These diseases are characterized by the “three Ds”: dermatitis, diarrhea, and dementia, followed in many cases by death. A century ago, pellagra was a common human disease; in the south ern United States, where maize was a dietary staple, about 100,000 people were afflicted and about 10,000 died between 1912 and 1916. In 1920 Joseph Goldberger showed pellagra to be caused by a dietary insufficiency, and in 1937 Frank Strong, D. Wayne Wolley, and Conrad Elvehjem identified niacin as the curative agent for blacktongue. Supplementation of the human diet with this inexpensive compound led to the eradication of pellagra in the populations of the developed world—with one significant exception. Pellagra is still found among alcoholics, whose intestinal absorption of niacin is much reduced, and whose caloric needs are often met with dis tilled spirits that are virtually devoid of vitamins, in cluding niacin. In a few places, including the Deccan Plateau in India, pellagra still occurs, especially among the poor.
FIGURE 13–17 Structures of niacin (nicotinic acid) and its derivative nicotinamide. The biosynthetic precursor of these compounds is tryptophan. In the laboratory, nicotinic acid was first produced by oxidation of the natural product nicotine—thus the name. Both nicotinic acid and nicotinamide cure pellagra, but nicotine (from cigarettes or elsewhere) has no curative activity.
