Figure 1.

Effect of hypoxia on pyruvate dehydrogenase (PDH) and ATP production. (a) The flux of PDH was determined, when oxygen availability was reduced from 100% (normoxia) to 0% (anoxia) of its normal value. To represent PDH effect on metabolism seen in cancer cells, uptake of amino acid was unconstrained (PDH + AA). In all conditions, the rate of PDH gradually decreased as the availability of oxygen decreased. (b) The rate of ATP production was determined by varying the flux of PDH from its maximum flux, while oxygen levels were kept constant at 100%. A maximum ATP production flux of 138.1 µmol min⁻¹ gDW⁻¹ was reached. For levels of PDH flux lower than 9 µmol min⁻¹ gDW⁻¹, the ATP level declined regularly, with an increasing negative slope. (c) Under hypoxia, oxygen availability was reduced to 10% of its normal value. ATP production increased above 17.2 µmol min⁻¹ gDW⁻¹, but for activity of PDH lower than 1.8 µmol min⁻¹ gDW⁻¹, it decreased to 17 µmol min⁻¹ gDW⁻¹. Interestingly, the decay observed in hypoxia is slower than in normoxia conditions.