2 1 8 Solubility o£ Proteins 



of electrolyte on the solubility, while variations in /? describe the effect of 

 temperature and pH on the solubility in a given salt solution. /? is the intercept 

 constant and therefore the logarithm of the hypothetical solubility at zero salt 

 concentration. It is "hypothetical" because many proteins are so soluble in 

 water that their solubility cannot be measured, and also because true globulins 

 are insoluble in water and show increased solubility in the presence of low 

 concentrations of salt. Variations in p may be conveniently used to describe 

 variation of solubility with pH. 



c. Effect of pH on Solubility 



Proteins become positively or negatively charged on either side of the iso- 

 electric point and these forms are more soluble than the electrically neutral 

 molecule. Solubility is increased by the addition of acid or base and the 

 protein behaves as though it had a divalent charge. This is obviously only 

 an apparent phenomenon, but it makes it possible to describe the solubility 

 of a protein at varying hydrogen ion concentration by the equation 



S =^^,^ an.^ ^ Kz'K,' (2) 



++Protein— Sn Ki'K.J ag.^ 



5 is the solubility, 5„ the solubility of the neutral molecule, ajj+ the activity 

 of the hydrogen ions, K/K/ the dissociation constants in acid solution, and 

 K/K^' the dissociation constants in alkaline solution. If these dissociation con- 

 stants are sufficiently far apart in value, solubility in alkaline solution may be 

 described by the equation 



Protein— ^ S_ ^ K^' K,' (3) 



++Protein Sn a 



and solubility in acid solution by the equation 



2 



H-' 



Protein++ S , ag.' (4) 



++Protem— Sn Ki'K^' 



Experimental results at different ionic strengths and different reactions 

 may be successfully analyzed in the region where equation 1 holds (since 

 K/ is independent of pH) by variations in p. This has been done in figure 3, 

 which describes the variation of solubility of both hemoglobin in phosphate 

 buffers^ and egg albumin in ammonium sulfate (S0rensen and H0yrup^), 

 with pH. 



^n is the logarithm of the hypothetical solubility of the neutral molecule 

 of the protein at zero salt concentration. Thus, 



S _ S _ antilog /3 1 



++Protein Sn antilog ;8„ 



The curves drawn through the points are theoretical according to equation 2. 

 The values for 5„ or Pn are not the values for minimum solubility as actually 



