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Catalytic promiscuity and heme-dependent redox regulation of H2S synthesis

After stopping a CYP3A4 inducer, as the effects of the inducer decline, codeine plasma concentrations may increase, with subsequently greater metabolism by cytochrome CYP2D6, resulting in greater morphine levels [see CLINICAL PHARMACOLOGY], which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression

Disturbances in the endoplasmic reticulum can be triggered by increased oxidative stress, deposition of saturated fatty acids, hypoxia, or other stimuli, which in turn cause the accumulation of unfolded proteins in the endoplasmic reticulum lumen that is filled with proteins, antioxidants, or essential metals

This kind of protection-damage dynamic transformation can well explain the phenomenon of the bilirubin paradox in PD (Moccia et al., 2015