DOUGLAS M. SURGENOR 



reactions, such as the number of groups reacting and the tight- 

 ness of the binding, and even some suggestions as to the mecha- 

 nisms involved. Many of the physiologically important inter- 

 actions of albumin were brought to light by the pioneer investi- 

 gations of Bennhold and his collaborators at Hamburg (6), who 

 studied the binding of bile and heme pigments and of many 

 drugs and pharmacologic agents. The binding of hematin was 

 suggested by Fairley (12), who showed the presence of abnormal 

 amounts of methemalbumin in Blackwater fever. This reaction 

 has since (31) been shown to involve the very tight combination 

 of two molecules of hematin (Ferriprotoporphyrin IX) with 

 each albumin molecule. Similarly, albumin can bind up to 3 

 moles of bilirubin (23). Unlike hematin, however, bilirubin is 

 also bound by a-globulin, apparently more tightly than by 

 albumin, although both forms occur under physiological 

 conditions. 



Only recently has the significance of the interaction of 

 fatty acids with albumin become apparent. Binding was first 

 suggested by Forrest Kendall (18), who obtained crystalline 

 human albumin preparations (from plasma that has been stored 

 for some time prior to fractionation) which contained 1.8% to 

 2.9% fatty acid. This could be extracted only by vigorous 

 treatment, suggestive of a high affinity. Later Hughes (9), 

 working with albumin crystallized from fresh plasma, found only 

 about 0.4% fatty acid, corresponding to 1 mole per mole of 

 albumin. The difference in the two preparations may have 

 depended on the time which elapsed before the plasma was 

 fractionated, as we now know that fatty acid is one of the 

 products of the "clearing reaction." So termed because of a 

 decrease in turbidity of lipemic plasma, this reaction has been 

 studied in some detail by Anfinsen (3) and others. The optical 

 clearing is the result of an enzymatic reaction in which low den- 

 sity (high molecular weight) lipoproteins are transformed into 

 lower molecular weight products. Analytically this change is 

 accompanied by a decrease in the neutral triglyceride content. 

 The j(3-lipoprotein characterized by Oncley contains little or no 



660 



