In vitro Inhibitory Effect of Quinolinic Acid on Aldehyde Oxidase Activity of Guinea Pig Liver: A Proposed Mechanism

The aim of the present study was to investigate the interaction of quinolinic acid (QA) with partially purified guinea pig liver aldehyde oxidase in terms of superoxide anion production (02 ) , hydrogen peroxide (H20 2) formation and the overall substrate oxidation. Due to the structural similarity of QA to some aldehyde oxidase substrates, such as 2-pyrimidinone, the effect of QA on aldehyde oxidase activity has been investigated in the present study. The interaction between QA and aldehyde oxidase has been measured by spectophotometerically and tluorimetrically methods using phthalazine (a classical heterocyclic substrate) and indole-3-aldehyde (an excellent aldehyde substrate). The inhibitory effects of QA on indole-3 -aldehyde and phthalazine oxidation, superoxide anion production and hydrogen peroxide formation were found to be competitive inhibition in all three cases (Ki = 77-106 mu M, r ≥ 0.995, p 0.005). QA inhibitory effect on aldehyde oxidase suggests that it may playa role in inhibition of initial rates of superoxide anion formation but may increase overall production of this radical by aldehyde oxidase. QA had a dual effect on superoxide anion production from the two substrates; initial rates were reduced but after 5-8 minutes reaction rates were enhanced. Both effects were concentration dependent.