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.
Metabolic alterations have been recognized to underly the etiology of many diseases. Herein, cellular energy dissipation was evaluated as a novel non-specific global biomarker of metabolic alterations. Energy dissipation, measured as heat by microcalorimetry, was maximal during Saccharomyces cerevisiae adaptation to growth conditions before fast proliferation took place. This response was further augmented by 95 % in media where nutrient assimilation was more difficult, and by 133 % under sub-optimal non-carbon nutrient levels. In this last case, the increase in energy dissipation (1) reflected changes in amino acid and glycolytic metabolism and (2) anticipated changes in the growth curve significantly later observed by traditional microbiological measurements. It was, therefore, an early marker of adaptive responses that compensated for sub-optimal nutrient levels and maintained phenotypic stability. Compensatory responses buffer systems against perturbations and delay the onset of diseases. Microcalorimetry can, therefore, provide a biomarker development platform for early disease-diagnosis.
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