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Pathway Description
Nicotinate and Nicotinamide Metabolism
Homo sapiens
Metabolic Pathway
Nicotinate (niacin) and nicotinamide - more commonly known as vitamin B3 - are precursors of the coenzymes nicotinamide-adenine dinucleotide (NAD+) and nicotinamide-adenine dinucleotide phosphate (NADP+). NAD+ synthesis occurs either de novo from amino acids, or a salvage pathway from nicotinamide. Most organisms use the de novo pathway whereas the savage pathway is only typically found in mammals. The specifics of the de novo pathway varies between organisms, but most begin by forming quinolinic acid (QA) from tryptophan (Trp) in animals, or aspartic acid in some bacteria (intestinal microflora) and plants.
Nicotinate-nucleotide pyrophosphorylase converts QA into nicotinic acid mononucleotide (NaMN) by transfering a phosphoribose group. Nicotinamide mononucleotide adenylyltransferase then transfers an adenylate group to form nicotinic acid adenine dinucleotide (NaAD). Lastly, the nicotinic acid group is amidated to form a nicotinamide group, resulting in a molecule of nicotinamide adenine dinucleotide (NAD). Additionally, NAD can be phosphorylated to form NADP. The salvage pathway involves recycling nicotinamide and nicotinamide-containing molecules such as nicotinamide riboside. The precursors are fed into the NAD+ biosynthetic pathwaythrough adenylation and phosphoribosylation reactions. These compounds can be found in the diet, where the mixture of nicotinic acid and nicotinamide are called vitamin B3 or niacin. These compounds are also produced within the body when the nicotinamide group is released from NAD+ in ADP-ribose transfer reactions.
References
Nicotinate and Nicotinamide Metabolism References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Pronk AF, Stouthamer AH, Van Verseveld HW, Boogerd FC: Nicotinate catabolism is dispensable and nicotinate anabolism is crucial in Azorhizobium caulinodans growing in batch culture and chemostat culture on N2 as The N source. J Bacteriol. 1995 Jan;177(1):75-81. doi: 10.1128/jb.177.1.75-81.1995.
Pubmed: 7798152
Bogan KL, Brenner C: Nicotinic acid, nicotinamide, and nicotinamide riboside: a molecular evaluation of NAD+ precursor vitamins in human nutrition. Annu Rev Nutr. 2008;28:115-30. doi: 10.1146/annurev.nutr.28.061807.155443.
Pubmed: 18429699
Ma Y, Bao Y, Wang S, Li T, Chang X, Yang G, Meng X: Anti-Inflammation Effects and Potential Mechanism of Saikosaponins by Regulating Nicotinate and Nicotinamide Metabolism and Arachidonic Acid Metabolism. Inflammation. 2016 Aug;39(4):1453-61. doi: 10.1007/s10753-016-0377-4.
Pubmed: 27251379
Trechot P, Jouzeau JY, Brouillard C, Scala-Bertola J, Petitpain N, Cuny JF, Gauchotte G, Schmutz JL, Barbaud A: Role of nicotinic acid and nicotinamide in nicorandil-induced ulcerations: from hypothesis to demonstration. Int Wound J. 2015 Oct;12(5):527-30. doi: 10.1111/iwj.12147. Epub 2013 Sep 13.
Pubmed: 24028540
Rennick A, Kalakeche R, Seel L, Shepler B: Nicotinic acid and nicotinamide: a review of their use for hyperphosphatemia in dialysis patients. Pharmacotherapy. 2013 Jun;33(6):683-90. doi: 10.1002/phar.1258. Epub 2013 Mar 21.
Pubmed: 23526664
Shibata K, Fukuwatari T, Suzuki C: Pharmacological doses of nicotinic acid and nicotinamide are independently metabolized in rats. J Nutr Sci Vitaminol (Tokyo). 2014;60(2):86-93.
Pubmed: 24975217
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