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Pathway Description
Nicotinate and Nicotinamide Metabolism
Xenopus laevis
Metabolic Pathway
Nicotinate, also called nicotinic acid or niacin, is a form of vitamin B3 that is primarily obtained through whole and processed, as well as fortified foods. Another form of vitamin B3 is nicotinamide or niacinamide, which is also obtained in trace amounts from dietary sources. Nicotinamide is critically important in the structure of NAD(H) and NADP(H), which are both used as coenzymes in oxidation-reduction reactions such as the citric acid cycle and the electron transport chain.
L-aspartic acid from the aspartate metabolism pathway can be converted into iminoaspartic acid by a putative L-aspartate dehydrogenase, removing a hydrogen ion from it. After this, a quinolinate synthase, whose protein is currently unknown in Xenopus laevis, converts it to quinolinic acid, which can also be obtained from the tryptophan metabolism pathway. Quinolinic acid can interact with carboxylating nicotinate-nculeotide pyrophosphorylase, which converts it to nicotinate beta-D-ribonucleotide. This can then be converted to nicotinate D-ribonucleoside by a cytosolic 5'-nucleotidase, adding a water molecule and removing a phosphate. This nicotinate D-ribonucleoside can then be converted back to nicotinate beta-D-ribonucleotide by a nicotinamide riboside kinase, or converted to and from nicotinic acid by purine nucleoside phosphorylase. Nicotinate beta-D-ribonucleotide can alternatively be converted straight to and from nicotinic acid by nicotinate phosphoribosyltransferase. Nicotinate beta-D-ribonucleotide can also be converted to and from nicotinic acid adenine dinucleotide by nicotinamide-nucleotide adenylyltransferase. This can then be converted back by a nucleotide diphosphatase. The nicotinic acid adenine dinucleotide is then converted to NAD by glutamine-dependent NAD synthetase. NAD can be converted to NADP by NAD kinase 2 in the mitochondria, which can be converted to and from NAD by a NAD+ transhydrogenase, also in the mitochondria. NAD can also be converted to nicotinamide ribotide by a nucleotide diphosphatase, which can then be converted to and from NAD by nicotinamide-nucleotide adenylyltransferase. Nicotinamide ribotide can form nicotinamide riboside via catalysis by a cytosolic purine 5'-nucleotidase, which can be returned to nicotinamide ribotide by a ribon. It can also be converted to nicotinamide by a purine nucleoside phosphorylase, which removes ribose 1-phosphate from it. Nicotinamide ribotide can also be directly converted to and from nicotinamide by nicotinamide phosphoribosyltransferase which removes phosphoribosyl pyrophosphate from it. Additionally, NADP and nicotinic acid can form nicotinamide and nicotinic acid adenine dinucleotide phosphate, catalyzed by 2'-phospho-cyclic-ADP-ribose transferase. Nicotinamide can finally have a methyl group added to it by nicotinamide N-methyltransferase, forming 1-methylnicotinamide, which can then interact with aldehyde oxidase 5, forming either N1-methyl-4-pyridone-3-carboxamide or N1-methyl-2-pyridone-5-carboxamide, which are the final products of this pathway.
References
Nicotinate and Nicotinamide Metabolism References
BEHRMAN EJ, STANIER RY: The bacterial oxidation of nicotinic acid. J Biol Chem. 1957 Oct;228(2):923-45.
Pubmed: 13475371
Alhapel A, Darley DJ, Wagener N, Eckel E, Elsner N, Pierik AJ: Molecular and functional analysis of nicotinate catabolism in Eubacterium barkeri. Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12341-6. doi: 10.1073/pnas.0601635103. Epub 2006 Aug 7.
Pubmed: 16894175
Baitsch D, Sandu C, Brandsch R, Igloi GL: Gene cluster on pAO1 of Arthrobacter nicotinovorans involved in degradation of the plant alkaloid nicotine: cloning, purification, and characterization of 2,6-dihydroxypyridine 3-hydroxylase. J Bacteriol. 2001 Sep;183(18):5262-7. doi: 10.1128/jb.183.18.5262-5267.2001.
Pubmed: 11514508
Gherna RL, Richardson SH, Rittenberg SC: The bacterial oxidation of nicotine. VI. The metabolism of 2,6-dihydroxypseudooxynicotine. J Biol Chem. 1965 Sep;240(9):3669-74.
Pubmed: 5835946
Galeazzi L, Bocci P, Amici A, Brunetti L, Ruggieri S, Romine M, Reed S, Osterman AL, Rodionov DA, Sorci L, Raffaelli N: Identification of nicotinamide mononucleotide deamidase of the bacterial pyridine nucleotide cycle reveals a novel broadly conserved amidohydrolase family. J Biol Chem. 2011 Nov 18;286(46):40365-75. doi: 10.1074/jbc.M111.275818. Epub 2011 Sep 27.
Pubmed: 21953451
Sachelaru P, Schiltz E, Igloi GL, Brandsch R: An alpha/beta-fold C--C bond hydrolase is involved in a central step of nicotine catabolism by Arthrobacter nicotinovorans. J Bacteriol. 2005 Dec;187(24):8516-9. doi: 10.1128/JB.187.24.8516-8519.2005.
Pubmed: 16321959
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