Reduction of hydrogen production Aas a metabolic strategy of tumors for survival under low oxygen supply

In general it can be summarized that tumor cells switch to non-oxidative pathways, thereby avoiding NAD(P)H production:

Ribose 5-P synthesis

Ribose 5-P, the precursor for nucleic acid synthesis, is no longer produced by the oxidative pentose phosphate pathway.

Instead of using the NADPH-producing glucose 6-P dehydrogenase and 6-phosphogluconate dehydrogenase, tumor cells produce ribose 5-P via the non-oxidative pentose phosphate pathway from fructose 6-P and glyceraldehyde 3-P under the catalyzation of transketolase and transaldolase.

Metabolic scheme



The degradation of fatty acids to acetyl-CoA is called b-oxidation.

In the opposite to fatty acid synthesis, which takes place in the cytosol, b-oxidation is located in the mitochondria.

Metabolic scheme

Fatty acids are the most important source of hydrogen for cells.

For example, the degradation of one mole of palmitic acid produces 92 moles of hydrogen.

In tumor cells, mitochondrial degradation of fatty acids is reduced, presumably due to a reduction of fatty acid degrading enzymes, low AMP levels and an increase in fatty acid synthetase capacity.

Lipogenesis: regulation by AMP

Lipogenesis: a hydrogen-releasing pathway