Quinolinic acid phosphoribosyltransferase in rat brain.
Because of the possible participation of quinolinic acid in brain function and/or dysfunction, the characteristics of its catabolic enzyme, quinolinic acid phosphoribosyltransferase (QPRTase; EC 2.4.2.19), were examined in rat brain tissue. For this purpose, a sensitive radiochemical assay method, based on the conversion of quinolinic acid to nicotinic acid mononucleotide (NAMN), was developed. For brain QPRTase, the Mg2+ dependency, substrate specificity, and optimal assay conditions were virtually identical to those of the liver enzyme. Kinetic analyses of brain QPRTase revealed a Km of 3.17 +/- 0.30 microM for quinolinic acid and Km = 65.13 +/- 13.74 microM for the cosubstrate phosphoribosylpyrophosphate. The respective Vmax values were: 0.91 +/- 0.08 pmol NAMN/h/mg tissue for quinolinic acid and 11.65 +/- 1.55 fmol NAMN/h/mg tissue for phosphoribosylpyrophosphate. All kinetic parameters measured for the brain enzyme were significantly different from those determined for liver QPRTase, indicating structural differences or distinct regulatory processes for the brain and liver enzymes. Phthalic acid was a potent competitive inhibitor of brain QPRTase. Examination of the regional distribution of QPRTase in the rat CNS and retina indicated a greater than 20-fold difference between the area displaying the highest activity (olfactory bulb) and those of only moderate activity (frontal cortex, striatum, retina, hippo-campus). Enzyme activity was present at the earliest age tested, 2 days, and tended to increase in older animals. Brain QPRTase activity was preferentially located in the nerve-ending (synaptosomal) fraction. Enzyme activity was stable over extensive periods of storage at -80 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)
Foster
A C
AC
Zinkand
W C
WC
Schwarcz
R
R
D000375:Aging; D000818:Animals; D001921:Brain / Q000201:enzymology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D009537:Nicotinamide Mononucleotide / Q000031:analogs & derivatives / Q000378:metabolism; D010430:Pentosyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010754:Phosphoribosyl Pyrophosphate / Q000378:metabolism; D010795:Phthalic Acids / Q000494:pharmacology; D017378:Quinolinic Acid; D011805:Quinolinic Acids / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012160:Retina / Q000201:enzymology; D013379:Substrate Specificity; D014018:Tissue Distribution; D000098553:Nicotinate-Nucleotide Diphosphorylase (Carboxylating)
D010795:Phthalic Acids; D011805:Quinolinic Acids; D009537:Nicotinamide Mononucleotide; C002953:nicotinate mononucleotide; C032279:phthalic acid; D010754:Phosphoribosyl Pyrophosphate; D010430:Pentosyltransferases; D000098553:Nicotinate-Nucleotide Diphosphorylase (Carboxylating); D017378:Quinolinic Acid