Titration Curve of Human Serum Albumin at 37 C as Predicted by the Figge-Fencl Quantitative Physicochemical Model: Validation against Independent Experimental Data
by James J. Figge, MD, MBA, FACP

Copyright 2003 - 2009 James J. Figge.
Updated 22 December, 2007; 28 December, 2008.
Updated version published 15 January, 2009 on
www.Acid-Base.org and www.Figge-Fencl.org.


To test the validity of a quantitative model, one can determine whether the model accurately predicts independent high-quality experimental data. The Figge-Fencl Quantitative Physicochemical Model of Human Acid-Base Physiology (22 December, 2007) can predict the titration curve of human serum albumin at 37 degrees C. The titration curve calculated from the model gives the predicted number of charges per albumin molecule as a function of pH. The predicted titration curve over the pH range of 5.0 to 9.0 is compared below against independent experimental data of Fogh-Andersen, Bjerrum and Siggaard-Andersen, Clinical Chemistry, 1993; 39: 48-52. [ Full text is available online ]. These data points (from Figure 4 in the Clinical Chemistry article) give the intrinsic charge carried by human albumin at 37 degrees C, and are considered to be high-quality experimental results. As demonstrated in Figure 1 below, there is very close agreement between the predicted albumin titration curve calculated from the Figge-Fencl Quantitative Physicochemical Model (red curve) and the independent experimental data points of Fogh-Andersen and colleagues (blue diamonds). A similar comparison is shown in Figure 2 (green curve) for the older Figge-Mydosh-Fencl model (J Lab Clin Med, 1992; 120: 713-719). It can be seen that the predictions of the Figge-Mydosh-Fencl model deviate substantially from the independent experimental data of Fogh-Andersen and colleagues at pH < 6.9 and pH > 7.9. These results strongly imply that the Figge-Fencl model, which postulates the existence of low-titrating lysine residues, is a more accurate representation of the true acid-base titrating behavior of albumin over the pH range of 5.0 to 9.0.


titration curve

Figure 1. Predicted titration curve of human serum albumin at 37 degrees Celsius and ionic strength of approximately 0.15 over the pH range 5.0 to 9.0, as calculated by the Figge-Fencl Quantitative Physicochemical Model of Human Acid-Base Physiology (red curve). Predicted charge displayed by albumin is given in Eq / mol albumin. The predicted isoelectric point is at pH = 5.48. The independent experimental data points of Fogh-Andersen, Bjerrum and Siggaard-Andersen, Clinical Chemistry, 1993; 39: 48-52, are also shown (blue diamonds). [ Full text is available online ]. These experimental data points give the intrinsic charge carried by human albumin at 37 degrees C in the presence of physiologic concentrations of NaCl, KCl, and CaCl2. Note the close agreement between the titration curve predicted by the Figge-Fencl model and the independent experimental data points of of Fogh-Andersen and colleagues.


titration curve

Figure 2. Predicted titration curve of human serum albumin at 37 degrees Celsius and ionic strength of approximately 0.15 over the pH range 5.0 to 9.0, as calculated by the Figge-Fencl Quantitative Physicochemical Model of Human Acid-Base Physiology (red curve). Predicted charge displayed by albumin is given in Eq / mol albumin. The independent experimental data points of Fogh-Andersen, Bjerrum and Siggaard-Andersen, Clinical Chemistry, 1993; 39: 48-52, are also shown (blue diamonds). [ Full text is available online ]. These experimental data points give the intrinsic charge carried by human albumin at 37 degrees C in the presence of physiologic concentrations of NaCl, KCl, and CaCl2. The predicted titration curve of human serum albumin at 37 degrees C and ionic strength of approximately 0.15 as calculated by the Figge-Mydosh-Fencl model (green curve) is shown for comparison. Note that the predictions of the Figge-Mydosh-Fencl model deviate substantially from the independent experimental data of Fogh-Andersen and colleagues at pH < 6.9 and pH > 7.9.

Link to Figge-Fencl Model

Link to Statistical Validation of Model

Link to Albumin Titration Curve

Link to Online Model Application

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