期刊
CRITICAL REVIEWS IN TOXICOLOGY
卷 49, 期 10, 页码 819-929出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/10408444.2019.1692191
关键词
Glutathione transferase; gamma-glutamyltransferase; dipeptidase; cysteine S-conjugate N-acetyltransferase; NAT8; aminoacylase; transport; biomarker; mercapturomic profile; moonlighting protein
类别
The mercapturic acid pathway is a major route for the biotransformation of xenobiotic and endobiotic electrophilic compounds and their metabolites. Mercapturic acids (N-acetyl-l-cysteine S-conjugates) are formed by the sequential action of the glutathione transferases, gamma-glutamyltransferases, dipeptidases, and cysteine S-conjugate N-acetyltransferase to yield glutathione S-conjugates, l-cysteinylglycine S-conjugates, l-cysteine S-conjugates, and mercapturic acids; these metabolites constitute a mercapturomic profile. Aminoacylases catalyze the hydrolysis of mercapturic acids to form cysteine S-conjugates. Several renal transport systems facilitate the urinary elimination of mercapturic acids; urinary mercapturic acids may serve as biomarkers for exposure to chemicals. Although mercapturic acid formation and elimination is a detoxication reaction, l-cysteine S-conjugates may undergo bioactivation by cysteine S-conjugate beta-lyase. Moreover, some l-cysteine S-conjugates, particularly l-cysteinyl-leukotrienes, exert significant pathophysiological effects. Finally, some enzymes of the mercapturic acid pathway are described as the so-called moonlighting proteins, catalytic proteins that exert multiple biochemical or biophysical functions apart from catalysis.
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