Quinolinate phosphoribosyltransferase

Figure 8.2. Synthesis of NAD from nicotinamide, nicotinic acid, and qninolinic acid. Quinolinate phosphoribosyltransferase, EC 2.4.2.19 nicotinic acid phosphoribosyl-transferase, EC 2.4.2.11 nicotinamide phosphoribosyltransferase, EC 2.4.2.12 nicotinamide deamidase, EC 3.5.1.19 NAD glycohydrolase, EC 3.2.2.S NAD pyrophosphatase, EC 3.6.1.22 ADP-ribosyltransferases, EC 2.4.2.31 and EC 2.4.2.36 and poly(ADP-ribose) polymerase, EC 2.4.2.30. PRPP, phosphoribosyl pyrophosphate.

EC 1.13.11.6) Formation of pyridine mononucleotides QAPRT Quinolinate phosphoribosyltransferase nadC + -H... 

Quinolinate decarboxylation and conversion to nicotinic acid mononucleotide is catalysed by quinolinate phosphoribosyltransferase, a rate-limiting enzyme in the conversion of tryptophan to NAD the reaction requires Mg and is negatively regulated by nicotinamide. Next the transfer of adenylate from ATP by an intermediate of nicotinamide/nicotinate-mononucleotide-adenyl-transferases isoenzymes (NMNAT, see below) yields nicotinic acid adenine... 

Scheme 12.103. Nicotinate nucleotide formed by the phosphoribosyltransferase quinolinate phosphoribosyltransferase (EC 2.4.2.19).

EC 2.7.7.1). The nicotinamide nucleotide itself can be produced with a phosphoribosyltransferase such as the quinolinate phosphoribosyltransferase (EC 2.4.2.19) (Scheme 12.103) to nicotinate ribonucleoide, which is subsequently converted to the amide. Other transferases, for example, EC 2.4.2.1, purinenucleoside phosphorylase, have also been implicated in the same process. It is generally assumed that phosphorylation of the carboxylate precedes amination and that a suitable source of nitrogen is found. Details remain unavailable at this writing. 

Quinolinic acid was identified as a metabolite of tryptophan in the rat by Henderson and Hirsch in 1949 (65). Quinolinic acid has been known to be a key intermediate of the tryptophan-NAD and aspartate + dihydroxyacetone phosphate-NAD pathways since the clear demonstration in vitro by Nishizuka and Hayaishi in 1963 (50). It has been proven that quinolinic acid is transformed into nicotinic acid mononucleotide in the presence of 5-phosphoribosyl-l-pyrophosphate by quinolinate phosphoribosyltransferase (50). In 1978 Lapin (52) first reported that quinolinic acid induced seizures when injected directly into the brains of mice. Later, quinolinic acid was shown to increase neuronal activity when ionophoreti-cally applied to neurons in rats cerebral cortex, striatum, and hippocampus (53,66,67). Now, quinolinic acid is known as a potent neurotoxin and as a precursor of NAD in the liver. 

Sinclair, S.J., Murphy, K.J., Birch, C.D. et al (2000) Molecular characterization of quinolinate phosphoribosyltransferase (QPRtase) in Nicotiana. Plant Mol Biol, 44, 603-617. 

Figure 2 NAD metabolism. Tip = tryptophan, 3-HK = 3-hydroxykynurenine, 3-HA = 3-hydroxyanthranilic acid, ACMS = a-amino-P-carboxymuconate- -semialdehyde, AMS = a-aminomuconate- -semialdehyde, NaMN = nicotinic acid mononucleotide, NMN = nicotinamide mononucleotide, NaAD = nicotinic acid adenine dinucleotide. For other abbreviations, see Figure 1. (1) tryptophan oxygenase [EC 1.13.11.11], (2) formy-dase [EC 3.5.1.9], (3) kynurenine 3-hydroxylase [EC 1.14.13.9], (4) kynureninase [EC 3.7.1.3], (5) 3-hydroxyanthranilic acid oxygenase [EC 1.13.11.6], (6) nonenzymatic, (7) aminocarboxymuconate-semialdehyde decarboxylase [EC 4.1.1.45], (8) quinolinate phos-phoribosyltransferase [EC 2.4.2.19], (9) NaMN adenylyltransferase [EC 2.7.2.18], (10) NAD synthetase [EC 6.3.5.1], (11) NAD kinase [EC 2.7.1.23], (12) NAD" glycohydro-lase [EC 3.2.2.5], (13) nicotinamide methyltransferase [EC 2.2.1.1], (14) 2-Py-forming MNA oxidase [EC 1.2.3.1], (15) 4-Py-forming MNA oxidase [EC number not given], (16) nicotinamide phosphoribosyltransferase [EC 2.4.2.12], (17) NMN adenylytransferase [EC 2.7.71], (18) nicotinate phosphoribosyltransferase [EC 2.4.2.11], (19) nicotinate methyltransferase [EC 2.7.1.7], and nicotinamidase [EC 3.5.1.19]. Solid line, biosynthesis dotted line, catabolism.

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