Resolving the role of lipoxygenases in the initiation and execution of ferroptosis
R Microsomal epoxide hydrolase (mEH, encoded by EPHX1): Located in the endoplasmic reticulum, physically close to CYP450 enzymes Directly intercepts CYP450-generated epoxides as they are produced Primary substrates: arene oxides and aliphatic epoxides from xenobiotic metabolism Critical for detoxifying benzo[a]pyrene epoxides (from cigarette smoke, grilled food), aflatoxin B1 8,9-epoxide (from mycotoxins), styrene oxide (industrial solvent), and drug epoxides (carbamazepine, phenytoin) Expressed at highest levels in liver, lung, kidney, and GI tract Soluble epoxide hydrolase (sEH, encoded by EPHX2): Located in the cytosol and peroxisomes Primary substrates: endogenous epoxides derived from fatty acid metabolism Metabolizes epoxyeicosatrienoic acids (EETs) into dihydroxyeicosatrienoic acids (DHETs) Also hydrolyzes leukotoxin (epoxide of linoleic acid) and other fatty acid epoxides Expressed in liver, kidney, heart, and vascular endothelium mEH Mechanism and Xenobiotic Detoxification mEH uses a two-step catalytic mechanism
These antioxidants help neutralize harmful free radicals, reducing oxidative stress and supporting overall cellular health
Short sleep can raise stress hormones and lower pain tolerance the next day
The key is understanding that temperature dramatically affects copper peptide stability
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