Identification of human acyl-CoA synthetase isoform catalyzing CoA conjugation for propionic acid-class NSAIDs and evaluation of protein binding abilities of conjugate metabolites

Abstract

NSAIDs containing carboxyl groups may be conjugated with CoA as well as glucuronic acid, and their conjugates are likely related with toxicities. In this study, we clarified that, among 26 acyl-CoA synthetase (ACS) isoforms, ACSL1 was the highest expressing isoform in the human livers. Propionic acid-class NSAIDs were selectively conjugated with CoA by ACSL1. Protein binding abilities of CoA-conjugates of these NSAIDs were higher than those of their acylglucuronides (AG). Thus, CoA-conjugates produced by ACSL1 may be related with propionic acid-class NSAIDs-induced toxicity rather than AG.