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The AMPK activator metformin inhibits mTOR signaling and promotes oxidative metabolism over glycolysis

Rich et al

Contributing factors include: reduced nutritional intake (proteins, essential amino acids, competition between amino acid transporters, vitamin insufficiency [riboflavin: GSSG reductase, nicotinic acid: NADPH, pyridoxine (B 6 ): SAMe pathway], mitochondrial dysfunction: ATP deficiency, down regulation SAMe synthase, oxidation of SAMe pathway enzymes, enhanced GSH utilization: conjugation reactions (toxins, drugs), and overwhelming oxidative challenge

Besides the FSP1-CoQ pathway, recent evidence has revealed an alternative ferroptosis defense mechanism involving dihydroorotate dehydrogenase (DHODH) and coenzyme Q10

Specifically, small apoAI containing HDL particles are the most efficient at accepting lipid hydroperoxides, which are reduced to their inactive lipid hydroxides via oxidation of the methionine residues in apoA-I (850)