How even people whose tissues are oxygenated properly can be running HIF-dependent degenerative metabolism

It involves yet another misnamed protein – HIF1, hypoxia inducible factor.

In well-oxygenated tissues a protein named HIF should be turned over rapidly,

Maybe, maybe not. If HIF-1 is actually ROSHIF-1, ROS and/or hypoxia inducible factor, then hypoxia is not required to stabilize HIF-1alpha, and if in fact sustained ROS is all that is really needed to prevent the turnover of the alpha subunit of ROSHIF-1, enough ROS to overwhelm our puny antioxidant defenses, and keep the Fe2+ in the prolyl hydroxylase in the Fe3+ state, inhibiting the hydroxylation of either of the two prolines in HIF-1a and thus inhibiting the turnover of HIF-1alpha that is set up by ubiquitination by VHL-ubiquitin ligase.

The antidote: Better antioxidants! Antioxidants that work 24/7 and work a lot better than vitamin C and N-acetylcysteine. But at least frequent dosing of vitamin C, contrary to current opinion.

The whole problem is set up by our not making our own vitamin C – as vitamin C is exhausted within cells suffering from excessive ROS, HIF1 is activated, glucose uptake is stimulated, as is glycolysis, mitochondrial respiration is reduced by both selective mitophagy and inactivation of pyruvate dehydrogenase by stimulation of pyruvate dehydrogenase kinase, and sugar fermentation and substrate level phosphorylation become the new main pathway to supply most of the cell’s energy, with reactive aldehyde formation, export of reactive aldehydes, reaction of reactive aldehydes with key LDL arginines, increasing its atherogenicity.

That is how degenerative metabolism can take over even normoxic cells. The definition of normoxic is tissue-specific. Normoxic varies at least from a paltry 1% in cartilage to more than 10% in arterial blood.


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