Functions Of Niacin
Niacin, like thiamin and riboflavin, also functions as a coenzyme in energy metabolism. In its amide form, niacin is part of the coenzymes NAD (nicotinamide adenine dinucleotide) and NADP (nicotinamide adenine dinucleotide phosphate), which serve as hydrogen carriers in numerous reactions catalyzed by substrate-specific dehydrogenases. NAD+ is required in all the major metabolic pathways that result in oxidative breakdovm of hexoses, amino acids, and fatty acids, including glycolysis, oxidative decarboxylation of pyruvate, citric acid cycle, deamination of amino acids, and ,B-oxidation of fatty acids. It also participates in the oxidation of a variety of other biologic substances, such as ethanol and retinol (vitamin A). NADP+ can substitute for NAD-in some ofthese reactions, and it is the active form in two reactions ofthe hexose monophosphate shunt. The resulting reduced coenzymes either channel hydrogen to the mitochondrial electron transport chain (from NADH + H+ to FMN) to produce ATP, or they are used as specific reducing agents in a variety of reactions, such as the conversion of pyruvate to lactate. Reduced NADP (NADPH + H+) is required for the synthesis of fatty acids, cholesterol, and steroid hormones. Hence niacin is essential in every cell and tissue of the body.
In niacin deficiency, some tissues are affected more than others, especially the skin, the gastrointestinal tract, and the nervous system. Early signs of niacin deficiency are nonspecific and include lassitude, anorexia, weakness, mild digestive disturbances, and such emotional changes as anxiety, irritability, and depression.
Large doses of nicotinic acid (100 to 200 the recommended allowance) administered orally have resulted in the lowering of serum cholesterol and betalipoprotein levels. The mechanism of this action is not understood, and the amide form is ineffective. Undesirable effects oflarge doses of nicotinic acid on the metabolism of the heart muscle have been observed. In human subjects, intravenously administered nicotinic acid caused the depletion of cardiac muscle glycogen and endogenous lipid because the use offree fatty acids from the blood as an energy source was inhibited. In addition, Winter and Boyer have reported a case history in which large doses of nicotinamide (3 g to 9 g) taken in the treatment of schizophrenia caused liver toxicity. Consequently this vitamin is not an innocuous therapeutic agent.
