Stable Isotope-Labeled Tryptophan as a Precursor for Studying the Disposition of Quinolinic Acid in Rabbits
A major pathway for metabolism of the essential amino acid tryptophan via the kynurenine pathway leads to the production of quinolinic acid as a precursor for nicotinamide containing nucleotides (Nishizuka and Hayaishi, 1963). Quinolinic acid, an agonist at the NMDA receptor, is also a neuro-toxin and convulsant (Stone and Connick, 1985). It has been postulated to be involved in several neurodegenerative diseases (Schwarcz et al., 1984). Recently, elevated concentrations of quinolinic acid have been found in the cerebrospinal fluid of patients with acquired immune deficiency syndrome (Heyes et al., 1989). Little is known of the kinetics of the in vivo disposition of quinolinic acid (i.e. rates of formation, distribution and elimination). The use of stable isotope-labeled precursors offers many advantages in the study of the disposition of endogenous compounds (Wolfe, 1984). We have begun investigations into the use of stable isotope-labeled tryptophan as a precursor for the in vivo production of labeled quinolinic acid in rabbits with a view of developing methods applicable for studying the disposition of quinolinic acid in man.
KeywordsQuinolinic Acid Kynurenine Pathway Chemical Ionization Mass Spectrometry Essential Amino Acid Tryptophan Single Rabbit
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