What is the mercapturic acid pathway?
The mercapturic acid pathway is a major route for the biotransformation of xenobiotic and endobiotic electrophilic compounds and their metabolites. Several renal transport systems facilitate the urinary elimination of mercapturic acids; urinary mercapturic acids may serve as biomarkers for exposure to chemicals.
How are mercapturic acids created?
Mercapturic acid is a condensation product formed from the coupling of cysteine with aromatic compounds. It is formed as a conjugate in the liver and is excreted in the urine. Glutathione adducts lose glutamate and glycine portions, and are acetylated to form mercapturic acids, which are excreted.
How does metabolism of GSH conjugates to mercapturic acid?
2): Glutathione conjugates are transported to the kidney, where they are rapidly metabolized to cysteine conjugates by the abundant yGT and dipeptidase activities in this organ; cysteine conjugates are reabsorbed from the renal tubular lumen, returned to the circulation, and transported back to the liver for …
Is mercapturic acid toxic?
The mercapturic acid of tetrafluoroethylene (TFE-NAC) appeared to be the most potent nephrotoxin, causing toxicity upon an i.p. dose of 50 mumol/kg.
Is glutathione an enzyme?
Glutathione is manufactured in the liver after ingestion of the appropriate amino acids and sulfur-containing foods. This underappreciated water-soluble compound serves as an antioxidant and regenerator of vitamin E and carotenoids, as well as an intracellular enzyme.
What is GSH and GSSG?
Reduced glutathione (GSH) is considered to be one of the most important scavengers of reactive oxygen species (ROS), and its ratio with oxidised glutathione (GSSG) may be used as a marker of oxidative stress.
Which metabolic pathway produces glutathione?
GSSG is converted to its reduced state by glutathione reductase, using NADPH generated primarily by the pentose phosphate pathway (Figure 2). GSH is a tripeptide composed of glutamate, cysteine, and glycine.
Which compound is detoxified by glucuronidation?
Hanioka et al. (2008) proposed that the glucuronidation of bisphenol A (an environmental endocrine disruptor) by UGT2B15 serves as a major detoxification pathway of this molecule. UGTs are notably inhibited by various compounds.
What are mercapturic acids and how are they formed?
Mercapturic acids (N-acetyl-l-cysteine S-conjugates) are formed by the sequential action of the glutathione transferases, γ-glutamyltransf … The mercapturic acid pathway is a major route for the biotransformation of xenobiotic and endobiotic electrophilic compounds and their metabolites.
How does glutathione convert to mercapturic acid?
Conjugation with glutathione, mediated by one of the glutathione S-transferases, is the first step in a sequence leading to a mercapturic acid. Several environmental chemicals are metabolized in this way.
How does the mercapturate pathway work?
The mercapturate pathway begins with the formation of a thioether bond between GSH and a xenobiotic in a reaction catalyzed (or enhanced) by glutathione S -transferases (GSTs).
Is the mercapturate pathway a biochemical defense against electrophilic xenobiotics?
Notwithstanding how one classifies the transformations of xenobiotics through the mercapturate pathway, it is clear that the mercapturate pathway is a biochemical defense against potentially harmful electrophilic xenobiotics.
