THE CHEMICAL SPECIFICITY OF THE INTERACTION OF DIVERSE HUMAN PLASMA PROTEINS

The chemical methods that have been developed for the separation, concentration and purification of the protein, glycoprotein, mucoprotein, and lipoprotein components of any biologic system, by fractionation in alcohol-water mixtures at controlled pH, salt, and protein concentration, at the subzero temperatures necessary to prevent denaturation, have thus far led to the recognition and concentration of over twenty-five different protein components of human plasma. These include albumins of more than one kind; immune globulins which differ in their physical properties and interactions with antigens: lipoproteins which differ in their physical properties and interactions with steroids; enzymes with protease, peptidase, lipase, phosphatase and esterase activity; thrombin, fibrinogen, and the antihemophilic globulin concerned with blood coagulation; iodoprotein and the recently crystallized metal-combining protein which interacts with both copper and iron and is presumably concerned with transport in the plasma.

This number of plasma proteins is far greater than can be detected electrophoretically or in the ultracentrifuge. Chemical fractionation has yielded at least four β₁-globulins and at least two α₁-and three α₂-globulins. The α₂-globulins include a mucoprotein and glycoproteins of more than one kind; the α₁-globulins, the bilirubin-containing globulin in Fraction V-_I and the lipoprotein in Fraction IV-_I. The β₁-globulins include the carotene-rich euglobulin which combines with three times its weight of lipid as well as a high molecular weight lipid-free β₁-globulin, both of which are concentrated in Fraction III-o. Fraction III also contains β₁-globulins of different molecular properties. The iron-binding component of the plasma, crystal ized from fraction IV-₇, is a lipid-free β₁-globulin and is more closely related to the albumins than to other globulins from the point of view of osmotic activity. Electrophoretically indistinguishable, these different β₁-globulins have no other common property. The lipid-binding plasma component is a β₁-euglobulin, the iron-binding β₁-component a pseudoglobulin. They differ in size, shape, in solubility, in chemical composition and interaction, and in physiological function.

The separation and concentration of the various proteins of human plasma was undertaken during this war in order to render as many as possible available as therapeutic agents and thus to increase our knowledge and control of the composition of the blood in health and in disease. Many more have been separated and are being studied chemically than have thus far been brought to clinical trial. Their study renders possible the further investigation of the chemical specificity of the interactions of the plasma proteins, which are responsible for many of the tests that have in the past, or may in the future, prove of value in the clinic in the study of pathological sera and the understanding of the specific protein component that is either elevated or deficient in this condition.