Metabolic functions of niacin
The best-defined role of niacin is in the metabolism of metabolic fuels, as the functional nicotinamide part of the coenzymes NAD and NADP, which play a major role in oxidation and reduction reactions. The oxi-dized coenzymes have a positive charge on the nico-tinamide ring nitrogen and undergo a two-electron reduction. The oxidized forms are conventionally shown as NAD(P)+ and the reduced forms either as NAD(P)H2 or, more correctly, as NAD(P)H + H+, since although it is a two-electron reduction, only one proton is incorporated into the ring, the other remain-ing associated with the coenzyme.
In general, NAD+ acts as an electron acceptor in energy-yielding metabolism, being oxidized by the mitochondrial electron transport chain, while the major coenzyme for reductive synthetic reactions is NADPH. An exception to this general rule is the pentose phosphate pathway of glucose metabolism, which results in the reduction of NADP+ to NADPH, and is the source of half the reductant for fatty acid synthesis.
In addition to its coenzyme role, NAD is the source of ADP-ribose for the ADP-ribosylation of a variety of proteins and poly(ADP-ribosylation) and hence activation of nucleoproteins involved in the DNA repair mechanism.
In the nucleus, poly(ADP-ribose)polymerase is activated by binding to breakage points in DNA. The enzyme is involved in activation of the DNA repair mechanism in response to strand breakage caused by radical attack or UV radiation. In cells that have suf-fered considerable DNA damage, the activation of poly (ADP-ribose) polymerase may deplete intracel-lular NAD to such an extent that ATP formation is impaired, leading to cell death.
ADP-ribose cyclase catalyzes the formation of cyclic ADP-ribose from NAD, and of nicotinic acid adenine dinucleotide phosphate from NADP (by cat-alyzing the exchange of nicotinamide for nicotinic acid). Both of these compounds act to raise cytosolic calcium concentrations by releasing calcium from intracellular stores, acting as second messengers in response to nitric oxide, acetylcholine, and other neurotransmitters.