Table 1.

Model parameter values used in the simulations, most of which are as presented in the Dash and Bassingthwaighte (2010) paper; model parameters that are re-estimated based on fittings of the model to the experimental data in Figs. 1 and 3 are shown with footnotes. Unless otherwise noted, the kinetic parameter values are at T = 37 °C.

Parameter	Definition	Value	Unit
$K_1^{″}$	Ionization constant of H2CO3	5.5×10−4	M
$K_1^{\prime }$	Equilibrium constant for the CO2 hydration reaction: ${\text{CO}}_2+{\mathrm{H}}_2\mathrm{O}\leftrightarrow {\mathrm{H}}_2{\text{CO}}_3(K_1^{\prime }=K_1/K_1^{″})$	1.4×10−3	Unitless
K1	Equilibrium constant for the overall CO2 hydration reaction: ${\text{CO}}_2+{\mathrm{H}}_2\mathrm{O}\leftrightarrow {{\text{HCO}}_3}^{-}+{\mathrm{H}}^{+}(K_1=K_1^{\prime }·K_1^{″})$; pK1 = −log10(K1) = 6.1 − 0.0434(pHpl−7.4) + 0.0014(T−37)(pHpl−7.4)	7.94×10−7 (pHpl = 7.4; T = 37°C)	M
$K_2^{″}$	Ionization constant of HbNHCOOH	1×10−6	M
$K_2^{\prime }$	Equilibrium constant for the CO2-Hb binding reaction: ${\text{CO}}_2+{\text{HbNH}}_2\leftrightarrow \text{HbNHCOOH}(K_2^{\prime }=K_2/K_2^{″})$	21.5# 23.65*	M−1
K2	Equilibrium constant for the overall CO2-Hb binding reaction: ${\text{CO}}_2+{\text{HbNH}}_2\leftrightarrow {\text{HbNHCOO}}^{-}+{\mathrm{H}}^{+}(K_2=K_2^{\prime }·K_2^{″})$	21.5×10−6# 23.65×10−6*	Unitless
$K_3^{″}$	Ionization constant of HbO2NHCOOH	1×10−6	M
$K_3^{\prime }$	Equilibrium constant for the CO2-HbO2 binding reaction: ${\text{CO}}_2+{\text{HbO}}_2{\text{NH}}_2\leftrightarrow {\text{HbO}}_2\text{NHCOOH}(K_3^{\prime }=K_3/K_3^{″})$	11.3# 14.7*	M−1
K3	Equilibrium constant for the overall CO2-HbO2 binding reaction: ${\text{CO}}_2+{\text{HbO}}_2{\text{NH}}_2\leftrightarrow {\text{HbO}}_2{\text{NHCOO}}^{-}+{\mathrm{H}}^{+}(K_3=K_3^{\prime }·K_3^{″})$	11.3×10−6# 14.7×10−6*	Unitless
$K_{4,\mathrm{S}}^{\prime }$	Equilibrium constant for the overall O2-Hb binding reaction: O2 + HbNH2 ↔ HbO2NH2 at standard physiological conditions (otherwise it is a function of PO2, PCO2, pHrbc, [DPG]rbc and T)	2.03×105	M−1
$K_5^{″}$	Ionization constant of HbNH3+	2.4×10−8# 2.64×10−8*	M
$K_6^{″}$	Ionization constant of HbO2NH3+	1.2×10−8# 1.56×10−8*	M
nH	Hill coefficient with variable cooperativity hypothesis for O2 binding to Hb: nH = α − β×10−PO2/γ (Eq. 11)	Variable	Unitless
α	Parameter governing PO2-dependent variable Hill coefficient nH with variable cooperativity hypothesis for O2 binding to Hb	2.82$	Unitless
β	Parameter governing PO2-dependent variable Hill coefficient nH with variable cooperativity hypothesis for O2 binding to Hb	1.20$	Unitless
γ	Parameter governing PO2-dependent variable Hill coefficient nH with variable cooperativity hypothesis for O2 binding to Hb	29.25$	mmHg
P50,S	Level of PO2 at which Hb is 50% saturated by O2 at standard physiological levels of PCO2, pHrbc, [DPG]rbc and T	26.8$	mmHg
PO2,S	Standard partial pressure of O2 in blood	100	mmHg
PCO2,S	Standard partial pressure of CO2 in blood	40	mmHg
pHpl,S	Standard pH in plasma	7.4	Unitless
pHrbc,S	Standard pH in RBCs, related to the standard plasma pH by: pHrbc,S = 0.795pHpl,S +1.357	7.24	Unitless
[DPG]rbc,S	Standard 2,3-DPG concentration in RBCs	4.65×10−3	M
TS	Standard temperature of blood	37	°C
pHrbc	pH in RBCs, related to plasma pH by: pHrbc = 0.795pHpl + 1.357)	Variable	Unitless
Rrbc	Gibbs-Donnan ratio for electrochemical equilibrium of protons or bicarbonate ions across the RBC membrane (Rrbc = [H+]pl/[H+]rbc = [HCO3−]rbc/[HCO3−]pl; Rrbc = 10−(pHpl−pHrbc) = 10−(0.205·pHpl−1.357))	Variable (0.692 at pHpl = 7.4)	Unitless
αO2,S	Solubility of O2 in water at standard temperature (37 °C)	1.46×10−6	M/mmHg
αCO2,S	Solubility of CO2 in water at standard temperature (37 °C)	3.27×10−5	M/mmHg
HctS	Standard hematocrit (volume fraction of RBCs in blood)	0.45	Unitless
[Hb]bl,S	Standard hemoglobin concentration in blood	2.33×10−3	M
[Hb]rbc,S	Standard hemoglobin concentration in RBCs ([Hb]rbc=[Hb]bl/Hct)	5.18×10−3	M
Wpl	Fractional water space of plasma	0.94	Unitless
Wrbc	Fractional water space of RBCs	0.65	Unitless
Wbl	Fractional water space of blood: Wbl = (1−Hct)·Wpl + Hct·Wrbc	0.81	Unitless
[O2]tot	Total O2 concentration of whole blood: [O2]tot = Wbl·αO2·PO2 + 4·Hct·[Hb]rbc·SHbO2	Variable	M
[CO2]tot	Total CO2 concentration of whole blood: [CO2]tot = Wbl·αCO2·PCO2 + ((1−Hct)Wpl+Hct·Wrbc·Rrbc)(K1·αCO2·PCO2/[H+]pl) + 4·Hct·[Hb]rbc·SHbCO2 (parameter K1 defined above)	Variable	M

^#Estimated based on model fittings to the data of Bauer and Schröder (1972) at T = 37 °C (see Fig. 3E)

^*Estimated based on model fittings to the data of Matthew et al. (1977) at T = 30 °C (see Fig. 3F)

^$Estimated based on model fittings to the data of Severinghaus and colleagues (Roughton et al., 1972; Roughton & Severinghaus, 1973; Severinghaus, 1979) in normal human blood at standard physiological conditions