Mechanism of toxification induced by involvement of a medium chain acyl-CoA synthetase

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The mechanism of toxification induced by involvement of a medium chain acyl-CoA synthetases catalyzing the amino acid conjugation has been investigated. However, little information is available about the medium chain acyl-CoA synthetases. Therefore, each medium chain acyl-CoA synthetase was purified from liver and kidney mitochondria of mouse, rat and bovine, and characterized (the substrate specificity, the pH optimum and the inhibition, etc). The further findings are as follows :1.There was the slight difference in the substrate specificity between three species.2.The relative expression of the medium chain acyl-CoA synthetases differed between liver and kidney.3.All substrates activated by this enzyme contain a flat hydrophobic region coplanar to the carboxylate group and have negative values for the charge on the carbon atom in the β-position of carboxylic acids.4.The activities of this enzyme were inhibited competitively by the nonsteroidal anti-inflammatory drugs and the quinolone antimicrobial drugs having the hydroxy or ketone groups at the β-position of carboxylic acids. Then, the inhibition of this enzyme might be one of some possible mechanisms for the development of Reye's syndrome.5.The combination of enoxacine and felbinac inhibited strongly this enzyme, suggesting that it might be one of some mechanisms for the induction of convulsion by NQs-NSAIDs.6.This enzyme may be predominantly responsible for incorporation of benzoic acids having the large alkyl or alkoxyl groups into triacylglycerides.7.The formation rates and the stability of acyl-CoAs were the factors that determine the metabolic fate (either detoxification or toxification) of xenobiotics containing a carboxylic group.