Nicotinate and Nicotinamide Metabolism


Nicotinate (niacin) and nicotinamide are precursors of the coenzymes nicotinamide-adenine dinucleotide (NAD+) and nicotinamide-adenine dinucleotide phosphate (NADP+). When NAD+ and NADP+ are interchanged in a reaction with their reduced forms, NADH and NADPH respectively, they are important cofactors in several hundred redox reactions. NAD+ is synthesized through two metabolic pathways. It is produced either in a de novo pathway from amino acids, or in salvage pathways by recycling preformed components such as nicotinamide back to NAD+. Most organisms synthesize NAD+ de novo from simple components. The specific set of reactions differs among organisms, but a common feature is the generation of quinolinic acid (QA) from tryptophan (Trp) in animals, or aspartic acid in some bacteria (intestinal microflora) and plants. The quinolinic acid is converted to nicotinic acid mononucleotide (NaMN) by transfer of a phosphoribose group. An adenylate group is then transferred to form nicotinic acid adenine dinucleotide (NaAD). Finally, the nicotinic acid group in NaAD is amidated to a nicotinamide (Nam) group, forming nicotinamide adenine dinucleotide. In a further step, some NAD+ is converted into NADP+ by NAD+ kinase, which phosphorylates NAD+. Besides assembling NAD+ de novo from simple amino acid precursors, cells also salvage preformed compounds containing nicotinamide. Although other precursors are known, the three natural compounds containing the nicotinamide ring and used in these salvage metabolic pathways are nicotinic acid (Na), nicotinamide (Nam) and nicotinamide riboside (NR). The precursors are fed into the NAD+ biosynthetic pathwaythrough adenylation and phosphoribosylation reactions. These compounds can be taken up from the diet, where the mixture of nicotinic acid and nicotinamide are called vitamin B3 or niacin. However, these compounds are also produced within cells, when the nicotinamide group is released from NAD+ in ADP-ribose transfer reactions.

Pathway legend Zoom in

Pathway Image

Pathway legend Zoom in

References

  1. Lehninger, A.L. (2005) Lehninger principles of biochemistry (4 th ed.). New York: W.H Freeman.
  2. Salway, J.G. (2004) Metabolism at a glance (3 rd ed.). Alden, Mass. : Blackwell Pub.