BLOOD 



of the /5-lipoprotcins, the etiology of the disease and the singular 

 distribution of atheromata at sites of vascular stress remain 

 completely obscure. Our ignorance of this obviously abnormal 

 pathway of lipid transport or metabolism is not surprising, 

 however, in view of the fact that we still do not know the normal 

 mechanisms by which the lipids are loaded and unloaded. 



Nature has adopted the device of interaction between a 

 specific protein and smaller molecular species to an extraor- 

 dinary degree. Qualitatively almost all such interactions 

 resemble those already cited; they differ primarily in quanti- 

 tative aspects such as the number of molecules bound per mole- 

 cule of protein, and the tightness of binding, or association 

 constant. The frequency of occurrence of binding can be seen 

 from a recent survey by Goldstein (16), where only in the case 

 of sodium and potassium did there appear not to be a bound 

 phase. Evidence of binding has been obtained for almost every 

 other substance normally found in plasma. For certain of these, 

 such as urea and glucose, the evidence is somewhat controversial, 

 owing in large part to the difficulty of demonstrating binding 

 when the degree and tightness of binding are small. Other 

 interactions, of which the binding of calcium by several plasma 

 proteins is a good example, fall in an intermediate category. 

 Here the binding is readily demonstrated (log K = 2.22), as 

 shown by McLean and Hastings (25), but in terms of mass, only 

 about half the calcium ions of plasma are in the bound form 

 under normal circumstances. 



One of the most important transport compartments has 

 proved to be the albumin of plasma, which enters into unusually 

 specific combination with a wide range of apparently unrelated 

 groups of small molecules, both physiological and otherwise. 

 The latter include many drugs, dyes, alkyl sulfates, fatty acids, 

 aromatic compounds, chloroform, and long-chain aliphatic alco- 

 hols. Theoretical studies on many of these interactions have 

 been greatly fostered by the availability of crystallized human 

 and bovine serum albumin, and much useful information has 

 been derived concerning the physical chemical aspects of the 



659 



