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Review
. 2019 Apr 23;8(2):10.
doi: 10.3390/ht8020010.

The mercapturomic profile of health and non-communicable diseases

Clara Gonçalves-Dias  1 , Judit Morello  2 , Valdir Semedo  3 , M João Correia  4 , Nuno R Coelho  5 , Emilia C Monteiro  6 , Alexandra M M Antunes  7 , Sofia A Pereira  8
Affiliations
Review

The mercapturomic profile of health and non-communicable diseases

Clara Gonçalves-Dias et al. High Throughput. .

Abstract

The mercapturate pathway is a unique metabolic circuitry that detoxifies electrophiles upon adducts formation with glutathione. Since its discovery over a century ago, most of the knowledge on the mercapturate pathway has been provided from biomonitoring studies on environmental exposure to toxicants. However, the mercapturate pathway-related metabolites that is formed in humans-the mercapturomic profile-in health and disease is yet to be established. In this paper, we put forward the hypothesis that these metabolites are key pathophysiologic factors behind the onset and development of non-communicable chronic inflammatory diseases. This review goes from the evidence in the formation of endogenous metabolites undergoing the mercapturate pathway to the methodologies for their assessment and their association with cancer and respiratory, neurologic and cardiometabolic diseases.

Keywords: N-acetyl-transferase 8; biomarkers; chronic inflammation; cysteine-S-conjugates; cysteinyl-leukotrienes; disulfides; dopamine; estrogen; mercapturate pathway; metabolomics.

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Conflict of interest statement

The authors declare no conflict of interests

Figures

Figure 1
Figure 1
The mercapturomic profile of health and non-communicable chronic diseases. Any cell can generate GSH-S-conjugates that are excreted into the circulation and metabolized at the external apical membrane of kidney proximal tubular cells (major route) and hepatocytes (minor route). The Cys-S-conjugates that are formed might be subsequently detoxified by the N-acetyl-transferase NAT8, allowing the formation of mercapturates that are eliminated in urine. The Cys-S-conjugates can also be reabsorbed into the bloodstream and distributed into several organs. Blood and urine can be used for biomonitoring of mercapturate pathway-related metabolites. CysS-X: cysteine-S-conjugates; GSH-X: glutathione-S-conjugates; N-AcCysS-X: mercapturates; NAT8: N-acetyl-transferase 8.
Figure 2
Figure 2
Mercapturomic profile of disease. This profile was defined by reviewing the mercapturate-pathway related metabolites that have already been associated with non-communicable diseases (prognostic, progression, therapeutic response) in clinical studies.
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