Nicotinamide picolinate carboxylase

Ikeda, M., Tsuji, H., Nakamura, S., Ichiyama, A., Nishizuka, Y., and Hayaishi, O. (1965) Studies on the biosynthesis of nicotinamide adenine dinucleotide. II. A role of picolinic carboxylase in the biosynthesis of nicotinamide adenine dinucleotide from tryptophan in mammals. J. Biol. Chem. 240 1395-401. 

Nicotinic Add Metabolism. The sequence of reactions leading to the formation of pyridine compounds is of particular interest as a source of nicotinic acid. Nutritional, isotopic, and genetic experiments have all shown that tryptophan and its metabolic derivatives including 3-hydroxy-anthranilic acid are precursors of nicotinic acid in animals and in Neuro-spora. The terminal steps in this sequence are not known. Under certain physiological conditions an increase in picolinic carboxylase appears to reduce nicotinic acid synthesis. This implies a common pathway as far as the oxidation of 3-hydroxyanthranilic acid. Whether quinolinic acid is a precursor of nicotinic acid is still uncertain. The enzyme that forms the amide of nicotinic acid also has not been isolated. Subsequent reactions of nicotinamide include the formation of the riboside with nucleoside phosphorylase and methylation by nicotinamide methyl-kinase. In animals W-methylnicotinamide is oxidized to the corresponding 6-pyridone by a liver flavoprotein. Nicotinic acid also forms glycine and ornithine conjugates. Both aerobic and anaerobic bacteria have been found to oxidize nicotinic acid in the 6-position. ... 

The dietary requirement for nicotinamide is also related to the requirement for tryptophan. Dietary tryptophan can be converted with varying efficiencies into nicotinamide, thus dietary tryptophan spares the requirement for nicotinamide. In the domestic fowl and grain-eating birds, there is rarely an excess of tryptophan. Pyridoxal phosphate (vitamin B ) is required for the interconversion of tryptophan to nicotinamide, and so the requirements for nicotinamide are moderated by the amounts of pyridoxal and of tryptophan residues present in the diet. The ability to convert tryptophan to nicotinamide also appears to depend on the level of picolinic acid carboxylase in the liver. This enzyme converts one of the intermediates, 2-amino-3-acroleylfumaric acid into a branch path and so competes with the main pathway. The levels of this enzyme are comparatively low in the domestic fowl but are much higher in the duck, which fits with the duck having a nicotinamide requirement about double that of the domestic fowl (Scott et al., 1982). 

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