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[9] The cAMPPKA Regulatory System In canonical beta-adrenergic stimulation, activation of a G s -coupled receptor increases adenylyl-cyclase activity and raises intracellular cyclic AMP

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Glucuronidation Increases BUT Is Insufficient While glucuronidation (the other safe pathway) does increase during pregnancy: This increase in glucuronidation CANNOT compensate for the simultaneous: 33% decrease in sulfation (another safe pathway) 80% increase in oxidation to toxic NAPQI **The Result:** When both safe pathways become saturated or overwhelmed, significantly more acetaminophen is forced through the toxic CYP2E1 pathway, creating 43% more NAPQIat precisely the time when glutathione reserves are most depleted

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