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Major causes of depletion include: - Chronic infections and inflammation (increased GSH consumption by immune cells) - Heavy metal exposure (mercury, lead, cadmium bind directly to GSH) - Alcohol (acetaldehyde, the toxic metabolite, requires GSH for detoxification) - Acetaminophen/paracetamol (forms NAPQI, neutralized by glutathione) - Aging (after 45, GSH synthesis declines 10-15% per decade) - Precursor deficiency: cysteine, glycine, glutamic acid, selenium, vitamin B6 NAC: The Key Glutathione Precursor N-acetylcysteine (NAC) is the acetylated form of L-cysteine, which is the rate-limiting factor in glutathione synthesis

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The cofactor of TKT is thiamine diphosphate (TDP), the active form of thiamine