巯基酸途径。
Critical Reviews in Toxicology
(
IF
4.1
)
Pub Date : 2020-01-16
, DOI:
10.1080/10408444.2019.1692191
Patrick E Hanna
1
,
M W Anders
2
Affiliation
Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN, USA.
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY, USA.
巯基酸途径是异生和内生亲电子化合物及其代谢物生物转化的主要途径。Mercapturic酸（Ñ乙酰基升-半胱氨酸小号-conjugates）由谷胱甘肽转移酶，γ-glutamyltransferases，二肽酶的连续作用形成，并且半胱氨酸š缀合物Ñ -acetyltransferase得到谷胱甘肽š -conjugates，升-cysteinylglycine小号-缀合物，l-半胱氨酸S-缀合物和巯基酸；这些代谢物构成“巯基体”特征。氨基酰酶催化巯基酸水解形成半胱氨酸S-缀合物。几种肾脏转运系统可促进尿中巯基尿酸的清除。尿巯基酸可作为暴露于化学物质的生物标志物。尽管巯基酸的形成和消除是脱毒反应，但是1-半胱氨酸S-缀合物可以通过半胱氨酸S-缀合物β-裂解酶进行生物活化。此外，一些l-半胱氨酸S-缀合物，特别是l-半胱氨酰-白三烯，发挥重要的病理生理作用。最后，巯基乙酸途径的某些酶被描述为所谓的“月光蛋白”，是除催化作用外还具有多种生化或生物物理功能的催化蛋白。
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The mercapturic acid pathway.
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, γ-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 β-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.
更新日期：2020-01-16