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Figure 4


Fig. 4. Model conditions where initial concentrations determine whether there is a switch-like response to O2 levels in the amount of HIF1{alpha} hydroxylated, or a gradual one. (A) When all enzymes are in excess, a steep drop in hydroxylation occurs as [O2] falls below 30 µM. For a range of initial unhydroxylated HIF1{alpha} between 0 and 1 µM, a steep, switch-like response is present. (B) An example with [HIF1{alpha}]0=0.1 µM. In comparison, when iron (C), PHD2 (D) or 2-oxoglutarate (E) is limiting, the hydroxylation shows no apparent switch-like behavior. (F) The effect of ascorbate is mixed. In A-E, [Asc]0=1000 µM, in excess. At low levels of the compound (below its Km for HIF1{alpha}, which is 180 µM), the oxygen response curve shows a more gradual, but non-linear reduction in hydroxylation. [Asc]0=1 µM is shown as an example.





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