The Biochemistry of Ferritin 199 



Methods of study relating the activity of protein hormones to their 

 chemical structure can be patterned after those used so successfully 

 with enzymes. The early suggestions concerning enzyme-substrate 

 interaction were brought to a focus by the Michaelis-Menten formula- 

 tion of enzyme-substrate compound formation and subsequently to 

 the implication in the reaction of specific groups on the enzyme surface. 



More difficult to study from a dynamic point of view are those cellu- 

 lar proteins which we loosely term "structural" or "storage" proteins. 

 Certainly such proteins have a biological function and can undergo 

 chemical 'alterations in addition to those of biosynthesis and degrada- 

 tion, but the problem of measuring such subtle changes or attempting 

 to relate the structure of these proteins to function is obviously very 

 difficult. The present report is concerned, nevertheless, with attempts 

 to study the relationship of protein structure to biological activity 

 where the protein is a "storage" protein, ferritin. 



Work in our laboratory, involving alterations in the circulation of 

 animals in hemorrhagic shock led to the identification of the iron 

 protein ferritin with a substance liberated in very small quantities into 

 the circulation during this state. The physiological activities which 

 our early work had associated with ferritin seemed unrelated at that 

 time to its well-known iron-storage function. These activities, which 

 might be termed hormonal if they could be shown to operate under 

 physiological rather than pathological conditions, are twofold: 



(a) The intravenous injection into a normal rat of very small quan- 

 tities of ferritin results in a temporary inhibition of the constrictor 

 response to the topical application of adrenaline on the part of the 

 muscular capillary blood vessels in the mesentery. This has been 

 called its "vasodepressor" effect. 



(6) The injection of ferritin into the circulation of the hydrated 

 rabbit or dog stimulates the neurohypophysis to the secretion of its 

 antidiuretic hormone, which in turn acts on the kidney tubules to 

 bring about an increased resorption of water, i.e., an oliguric or "anti- 

 diuretic" effect. 



With these two activities, non-quantitative and time-consuming as 

 their measurements may be, we were better able to investigate the 

 relationship of the functional groups in ferritin to activity than if we 

 had known only about its iron-storage activity. As will be seen, our 

 present findings make it likely that all three physiological activities 

 of ferritin are related to the same chemical groups and to similar 

 alterations in their structure. 



