Principles of Biochemistry, Volume 1 - A. Lehninger 1985

Biomolecules
Vitamins and trace elements: their role in enzyme function
Nicotinamide is the active group of the coenzymes NAD and NADP

A dietary deficiency of nicotinic acid (Fig. 10-6) causes a human disease known as pellagra (derived from the Italian phrase meaning "rough Skin"). Pellagra is prevalent in many Regions of the world where diets consist primarily of corn and contain little meat, milk, or eggs. For both the Prevention and Treatment of pellagra, either nicotinic acid or its amide, nicotinamide, can be used. To prevent any misconception that tobacco could serve as a dietary source of this vitamin, nicotinic acid was given an alternative common name: niacin.

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Fig. 10-6. A. Two forms of the vitamin that prevents pellagra. B. Structures of the active Coenzyme forms of this vitamin—nicotinamide adenine dinucleotide (NAD⁺) and nicotinamide adenine dinucleotide phosphate (NADP⁺). Both of these compounds contain two nucleotide residues, each consisting of a base (nicotinamide or adenine), a five-carbon sugar (D-ribose), and a phosphate group. The oxidized forms of the NUCLEOTIDES are shown. The reduced form of NAD is shown in Fig. 10-7.

Nicotinamide is a component of two structurally related Coenzymes: nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). The structures of these coenzymes are shown in Fig. 10-6. NADP differs from NAD by the presence of an additional phosphate group in the molecule. These coenzymes can exist in both oxidized (NAD⁺ and NADP⁺) and reduced (NADH and NADPH) forms. The nicotinamide moiety of these coenzymes acts as an intermediate carrier of a hydride ion, which is enzymatically cleaved from a substrate molecule by the action of specific dehydrogenases (Fig. 10-7). An example is the reaction catalyzed by malate dehydrogenase, which dehydrogenates malate, converting it into oxaloacetate; this reaction represents one of the stages in The oxidation of CARBOHYDRATES and Fatty acids. Malate dehydrogenase also catalyzes the reversible transfer of a hydride ion from malate to NAD⁺, yielding NADH; the second hydrogen atom is released from the hydroxyl group of the malate molecule as a free H⁺ ion:

A large number of such dehydrogenases are known, each exhibiting Specificity for a particular substrate. Some of these Enzymes utilize NAD⁺ as a coenzyme, others use NADP⁺, and still others can function with either coenzyme. In most NAD- (or NADP-) dependent dehydrogenases, the coenzyme binds to the protein moiety of the enzyme only during the catalytic cycle; however, certain enzymes are known in which the coenzyme is bound very tightly and permanently resides in the Active Site.

Fig. 10-7. General equation illustrating The Role of NAD⁺ as a coenzyme in enzymatic dehydrogenation reactions. Substrate molecules and reaction products are highlighted in red. Only the nicotinamide portion of the NAD⁺ molecule is shown explicitly, with the remainder of the molecule represented by R.