Table 1.
Parameters for the degradation of HIF1α in normoxia
| Constant | Value | Temperature (°C) | Reference |
|---|---|---|---|
| [H2O2]0 | 0.20 μM* | 37 | Gonzalez-Flecha and Demple, 1997 |
| [O2]0 | 200 μM | 37 | Tuckerman et al., 2004 |
| [Fe3+]0 | 0 μM | 37 | – |
| [Fe2+]0 | 50 μM | 37 | Tuckerman et al., 2004 |
| [2-OG]0 | 1000 μM | 37 | Tuckerman et al., 2004 |
| [Asc]0 | 1000 μM | 37 | Tuckerman et al., 2004 |
| [HIF1α]0 | 1 μM | 37 | Tuckerman et al., 2004 |
| [PHD2]0 | 1 μM; 4 nm (where stated for in vitro comparisons) | 37 | Tuckerman et al., 2004 |
| kon,Fe2 | 18 μM−1 min−1, estimate | 37 | – |
| koff,Fe2 | 36 min−1, estimate | 37 | – |
| kcat,Fe2 | 0, assumed | 37 | – |
| Km,Fe2 | 2 μM (0.03 μM) | 37 | Hirsila et al., 2005; Koivunen et al., 2004 |
| kon,DG | 1.8×10−1 μM−1 min−1, estimate | 37 | – |
| koff,DG | 10.8 min−1 estimate | 37 | – |
| kcat,DG | 0, assumed | 37 | – |
| Km,DG | 60 μM | 37 | Hirsila et al., 2003 |
| kon,O2 | 4.3×10−2 μM−1 min−1, estimate | 37 | – |
| koff,O2 | 10.8 min−1, estimate | 37 | – |
| kcat,O2 | 0, assumed | 37 | – |
| Km,O2 | 250 μM | 37 | Hirsila et al., 2003 |
| kon,AS | 1.8×10−2 μM−1 min−1, estimate | 37 | – |
| koff,AS | 3.6 min−1, estimate | 37 | – |
| kcat,AS | 0, assumed | 37 | – |
| Km,AS | 180 μM | 37 | Hirsila et al., 2003 |
| kon,Hα | 1.1×10−1 μM−1 min−1, estimate calculated | 37 | – |
| koff,Hα | 0.7 min−1, estimate | 37 | – |
| kcat,Hα | 0.098–0.164 min−1, estimate 0.08–10 min−1 min/max from experiments† | 37; 30 | Kersteen et al., 2004; Tuckerman et al., 2004 |
| Km,Hα | 7 μM | 37 | Hirsila et al., 2003 |
| kFe3 | 1.1×10−2 μM−1 min−1, 1.6×10−2 μM−1 min−1 | 30 | Beltran et al., 1998; Lovstad, 2003; Millero and Sotolongo, 1989‡ |
| kASFe | 6×10−3 μM−1 min−1 | 37 | Buettner and Jurkiewicz, 1996 |
| kon,VL | 42 μM−1 min−1 | 25 | Hon et al., 2002 |
| koff,VL | 1.3 min−1 | 25 | Hon et al., 2002 |
Values are experimentally determined or estimated, or estimated from model calculations as noted.
Assumed, as an approximation. Range of 0.13–0.25 μM given in the cited reference. Within this range, the effects on varying H2O2 initial concentration on the model response are relatively negligible.
Maximum is estimated from Kersteen et al. (Kersteen et al., 2004), where kcatHα=13±1 min−1 for (Pro-Pro-Gly) binding to PHD2; 9.2±1.2 min−1 for dansyl-GFPG-OE to PHD2. The model default value, 1 min−1, is closer to the minimum, estimated from Tuckerman et al. (Tuckerman et al., 2004).
For the Fenton reaction at pH 3–4, kFe3 is 76.52 M−1 s−1 (Beltran et al., 1998); this value is approximately threefold higher at pH 8 (Millero and Sotolongo, 1989). For pH 6.7 (the pH assumed for all other model kinetic parameters), kFe3 was estimated from Beltran et al. (Beltran et al., 1998) as 6.7/8*3*76.52 M−1s−1=1.1×10−2 μM−1 min−1, which corresponds with that reported by Lovstad (Lovstad, 2003).