Inhibition of quinolinate phosphoribosyl transferase by pyridine analogs of quinolinic acid.
The enzyme quinolinate phosphoribosyl transferase was purified from ATCC strain 23269. An HPLC method was developed for the analysis of the product of the enzyme reaction, nicotinate mononucleotide. Steady state kinetics in the forward reaction demonstrated a sequential mechanism for the enzyme. In order to gain more information on the mechanism of the enzyme reaction, a series of 2 substituted nicotinic acids and 2 substituted 3-nitropyridines were investigated as inhibitors of the reaction. The results indicate that potent inhibition results when the quinolinic acid analogs possessed a negatively charged group at the 2 position of the pyridine ring.
D002851:Chromatography, High Pressure Liquid; D007700:Kinetics; D009537:Nicotinamide Mononucleotide / Q000031:analogs & derivatives / Q000096:biosynthesis; D009539:Nicotinic Acids / Q000494:pharmacology*; D010430:Pentosyltransferases / Q000037:antagonists & inhibitors*; D010754:Phosphoribosyl Pyrophosphate; D011725:Pyridines / Q000494:pharmacology*; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000494:pharmacology*; D000098553:Nicotinate-Nucleotide Diphosphorylase (Carboxylating)
D009539:Nicotinic Acids; D011725:Pyridines; D011805:Quinolinic Acids; D009537:Nicotinamide Mononucleotide; C002953:nicotinate mononucleotide; D010754:Phosphoribosyl Pyrophosphate; D010430:Pentosyltransferases; D000098553:Nicotinate-Nucleotide Diphosphorylase (Carboxylating); D017378:Quinolinic Acid