Aminoacylases catalyze the hydrolysis of N-acyl-L-amino acids to give fatty acids and amino acids as products. It has been proposed that aminoacylases may participate in the catabolism of terminal N-acylpeptides or in the salvage of N-acetylated amino acids. The aminoacylases play a role in xenobiotic detoxication and bioactivation and are important in the interorgan processing of xenobiotic-derived amino acid conjugates. Aminoacylases participate in conjugation-dependent toxicity—for example, mercapturates may serve to deliver nephrotoxic cysteine S-conjugates to the kidney. In this mechanism, mercapturates delivered via the circulation to the kidney may be taken up by the probenecid-sensitive anion transport system located on the basolateral surface of renal proximaltubular cells. Although aminoacylase activity is found in many tissues, this chapter focuses largely on renal aminoacylases, which are the only aminoacylases that have been linked to xenobiotic bioactivation reactions.
