BLOOD 



fatty acid triglyceride. Working on this clue, Anfinsen found 

 that the clearing factor possesses lipase activity, the products being 

 free fatty acids, glycerol, mono- and di-glycerides. Albumin, 

 by binding fatty acids, is essential for the reaction to proceed. 

 Without it, or with albumin containing six to ten molecules of 

 sodium oleate, the clearing reaction was inhibited by the accumu- 

 lation of fatty acid. Fatty acid binding and transport must 

 therefore be considered one of the important physiological 

 functions of albumin. The potential size of this compartment 

 is considerable. The albumin in each liter of plasma can bind 

 approximately 1 g. of fatty acid. 



The quantitative relationships between extent of binding 

 and physiological function are perhaps no better illustrated than 

 with the chemotherapeutic agents. Since the site of action of 

 most drugs is not in the blood stream but in a tissue, binding to 

 a plasma protein may seriously interfere with the access of the 

 drug to other areas of the body. Only the unbound species is 

 freely diffusible, and it is the concentration of diffusible drug 

 which corresponds most nearly to the effective concentration. 

 This was clearly shown by Davis (11) in the case of several sulfa 

 drugs. The concentration in cerebrospinal fluid corresponded 

 quite well with the concentration of unbound drug in the blood, 

 despite wide variations in amount bound by blood components. 

 The fraction of drug which is bound acts as a reservoir since it is 

 generally in equilibrium with the diffusible species. It follows 

 that binding does not necessarily interfere with the effectiveness 

 of a drug; the latter is determined by the concentration of the 

 drug at the site of its action. If only a very low concentration 

 is needed for activity, the drug may be effective even though over 

 90% of the amount administered is bound. Conversely, where 

 high concentrations are required to produce pharmacological 

 activity, even relatively low binding may result in impaired 

 usefulness. 



The hormones present a curious anomaly. The term 

 hormone was introduced in 1904 by Bayliss and Starling (5) ; its 

 origin was the concept, derived from physiological observations, 



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