代謝活性中間体と単幕質付加体生成

概要

論文の詳細を見る
In the body, drugs and biological active substances having a carboxyl group in those molecules have been known to transform various metabolites. Commonly, these compounds such as α-aryl propionic acid derivatives are activated to corresponding intermediates like a coenzyme A thiol ester prior to both isomerizations and conjugations with amino acids. The acyl adenylate has been also noted as an intermediate of coenzyme A ligation. In addition, the carboxyl group is known to be metabolized to acyl glucuronides in hepatocyte. Both the acyl adenylate and the acyl glucuronide are chemically very active, and they may produce the protein-bound adducts by reaction with the nucleophilic groups such as an amino group on the protein molecule. The authors have synthesized acyl glucuronides and acyl adenylates of bile acids, which are endogeous carboxylic acid derivatives, biosynthesized from cholesterol in the hepatocyte, and investigated their reactivity with peptide or protein. Both results clearly indicated that these active intermediates produced protein-bound adducts nonenzymatically. The formation of such adducts has attracted attention as a possible explanation for hypersensitivity, and non-enzymatic post-translational modifications to proteins in the body.
日本質量分析学会の論文
2002-06-01