Effect of Sulfur Amino Acid Depletion and Acetaminophen on Plasma Glutatione

Study Summary

Availability of sulfur amino acids (SAA) is critical for glutathione/glutathione disulfide (GSH/GSSG) and cysteine/cystine (CYS/CYSS) redox in vivo and for many other physiologic functions including protein synthesis, nitrogen balance, digestion, osmotic regulation, detoxification, hormonal regulation, biologic methylations, and cell growth regulation. GSH conjugation and sulfate conjugation represent quantitatively important pathways for chemical detoxification, which imposes substantial burden upon SAA supply. The primary hypothesis is that SAA deficient diet and acetaminophen (APAP) administration will perturb Cys metabolism and GSH redox homeostasis in human plasma and urinary output of SAA metabolites. Because both of these variations affect SAA homeostasis, it is believed that the combination of these treatments will produce an interactive effect in which 2-day SAA deficiency will alter APAP metabolism, APAP will affect SAA homeostasis, and the treatments together will alter the global metabolic profile, as measured by 1H-NMR spectroscopy.