This page will look better in a graphical browser that supports web standards, but is accessible to any browser or internet device.

Served by Samwise.

Cardiac Physiome Society workshop: November 6-9, 2017 , Toronto


Oxygen binding to hemoglobin at 4 cooperative sites. alp > 1 for pos cooperativity, alp < 1 for neg coop.

Model number: 0030

Run JSim model Applet:
JSim Tutorial
Java runtime required. Web browser must support Java Applets.
(JSim model applet may take 10-20 seconds to load.)


   Hemoglobin, a protein with 4 interdependent binding sites, can become 
saturated with oxygen, i.e all of its binding sites can be occupied at high 
concentrations. The fractional saturation is calculated here by a cooperative
scheme by which there is a constant ratio of increases in affinity as each site
is filled in succession. The cooperativity factor "alp" is >1 for positive 
cooperativity, and < 1 for anticooperativity. 
   The results are compared with the result using a Hill equation with a 
Hill coefficient of 2.7. The value is chosen because the Hill equation 
with nH (Hill coefficient with nH = 2.7 fits oxyhemoglobin saturation curves well).
   The math is straightforward, based on the equation for single site binding, modified
in recognition that there are, at varying concentrations, 4 sites available to fill. When
one is filled, only 3 remain, reducing the odds from 4 to 3, and so on. The actual O2
carriage depends on the relative abundances of HbO, HbO2, etc, and the fact that there
is twice as much O2 on HbO2 as on HbO, etc. The sum of the products of the relative 
concentrations times the O2s being carried in each form is divided by 4*HbO4, the 
maximum that can be carried.
   This model serves as a basis of other cooperativity models wherein the filling of 
the first and successive sites causes (by cooperativity = positive feedback through
molecular conformational rearrangement) successively higher affinities. The ratio, "alp"
is not necessarily constant. For example the Adair eqautions are equivalent  to
having "alp as a variable.


The equations for this model may be viewed by running the JSim model applet and clicking on the Source tab at the bottom left of JSim's Run Time graphical user interface. The equations are written in JSim's Mathematical Modeling Language (MML). See the Introduction to MML and the MML Reference Manual. Additional documentation for MML can be found by using the search option at the Physiome home page.

Download File


Keener J and Sneyd J. Mathematical Physiology. New York, NY: 
Springer-Verlag, 1998, 766 pp.

Dash RK and Bassingthwaighte JB. Erratum to: Blood HbO2 and HbCO2 dissociation curves at 
varied O2, CO2, pH, 2,3-DPG and Temperature Levels. Ann Biomed Eng 38(4): 1683-1701, 2010. 

Hill AV. The diffusion of oxygen and lactic acid through tissues. 
Proc R Soc Lond (Biol) 104: 39-96, 1928.

Adair GS. The hemoglobin system.  VI.  The oxygen dissociation curve of 
hemoglobin. J Biol Chem 63: 529-545, 1925.

Hill AV. The possible effects of the aggregation of the molecules of haemoglobin on its
dissociation curves. J Physiol 40: iv-vii, 1910

Hill R. Oxygen dissociation curves of muscle hemoglobin. Proc Roy Soc Lond B
120: 472-480, 1936.

Roughton FJW, Deland EC, Kernohan JC, and Severinghaus JW. Some recent studies of the
oxyhemoglobin dissociation curve of human blood under physiological conditions and the
fitting of the Adair equation to the standard curve. In: Oxygen Affinity of Hemoglobin and
Red Cell Acid Base Status. Proceedings of the Alfred Benzon Symposium IV Held at the
Premises of the Royal Danish Academy of Sciences and Letters, Copenhagen 17-22 May,
1971, edited by Rorth M and Astrup P. Copenhagen: Munksgaard, 1972, p. 73-81.

Winslow RM, Swenberg M-L, Berger RL, Shrager RI, Luzzana M, Samaja M,and
Rossi-Bernardi L. Oxygen equilibrium curve of normal human blood and its evaluation by
Adair's equation. J Biol Chem 252: 2331-2337, 1977.

Related Models

Key Terms

hemoglobin, oxygen, carbon dioxide, saturation, Haldane, Bohr, acidity, pH, blood gases, Hill equation, solubility, cooperativity, Data

Model Feedback

We welcome comments and feedback for this model. Please use the button below to send comments:

Model History

Get Model history in CVS.


Please cite in any publication for which this software is used and send one reprint to the address given below:
The National Simulation Resource, Director J. B. Bassingthwaighte, Department of Bioengineering, University of Washington, Seattle WA 98195-5061.

[This page was last modified 02Nov16, 3:56 pm.]

Model development and archiving support at provided by the following grants: NIH/NIBIB BE08407 Software Integration, JSim and SBW 6/1/09-5/31/13; NIH/NHLBI T15 HL88516-01 Modeling for Heart, Lung and Blood: From Cell to Organ, 4/1/07-3/31/11; NSF BES-0506477 Adaptive Multi-Scale Model Simulation, 8/15/05-7/31/08; NIH/NHLBI R01 HL073598 Core 3: 3D Imaging and Computer Modeling of the Respiratory Tract, 9/1/04-8/31/09; as well as prior support from NIH/NCRR P41 RR01243 Simulation Resource in Circulatory Mass Transport and Exchange, 12/1/1980-11/30/01 and NIH/NIBIB R01 EB001973 JSim: A Simulation Analysis Platform, 3/1/02-2/28/07.