162 SECTIONAL ADDRESSES. 



that there may be other, hitherto undiscovered components of foodstuffs, 

 which are important as raw material for synthesis in the animal cell, but 

 they can be but few in number and present in small amount. Given this 

 list of raw materials can we in every instance indicate which is the likely 

 starting point for the synthesis of substances whose constitution is known 

 or partly known ? This question must still be answered in the negative 

 for such well-known products as cholesterol and the unconjugated acids of 

 bile. It is possible that the experiments of Channon who demonstrated 

 that addition of spinacene to the diet of rats caused the cholesterol content 

 of the liver to increase to double its usual amount may afford a clue to the 

 origin of this substance, but it is difficult to conceive of spinacene being 

 the raw material for this synthesis in the herbivorous animal. As for the 

 bile acids, we are in complete ignorance of the substance or substances 

 from which they are built up. Although closely allied in structure to 

 cholesterol it is clear from the careful experiments of Enderlen, Thann- 

 hauser and Jenke, who failed to observe any increase in the production of 

 bile acids in dogs after long periods in which cholesterol was added to the 

 diet, that they are not produced from this substance. 



With the purine bases, which are components of nuclear material and 

 therefore present in all cells, this question of indicating the probable raw 

 material for their synthesis must also be answered in the negative, but 

 with less emphasis than in the case of cholesterol and the bile acids. The 

 amino-acid histidine, which contains a five-membered ring similar to that 

 found in the purine bases, is their most likely precursor on structural 

 grounds. But we have as yet no experimental evidence that indicates 

 clearly their origin from this amino-acid in the body. ■ Until this has been 

 proved it is perhaps useless to speculate as to the chemical processes 

 involved in the transformation. The synthesis of cholesterol, that of the 

 bile acids and of purine bases are therefore still problems in the purely 

 chemical sense. When the chemist has indicated their likely solution it 

 will be the task of physiology to find out the mechanism by which the cell 

 brings about the necessary chemical processes. 



An example of a synthetic product which bears a fairly close structural 

 relationship to two of the amino acids which are found in proteins is 

 adrenaline. These two amino acids, phenylalanine and tyrosine have 

 practically the same carbon skeleton as adrenaline. Either of them might 

 give rise to adrenaline by successive oxidation, methylation of the amino 

 group and loss of carbon dioxide. That a part of the necessary oxidation 

 process can be brought about by means of an oxidising enzyme has already 

 been demonstrated. This enzyme, tyrosinase, will oxidise tyrosine to 

 3:4-dihydroxyphenylalaniue. It is therefore conceivable that the first 

 stage of the synthesis from tyrosine occurs in this way in the cell. The 

 enzyme does not attack phenylalanine so that this seems less likely as a 

 precursor than tyrosine although there is evidence that in other respects 

 the metabolism of these two amino acids is closely related. In N-methyl- 

 tyrosine we have an amino acid which is more nearly related to adrenaline 

 than tyrosine, since in both the amino group is methylated. By the 

 introduction of two atoms of oxygen in the appropriate positions and loss 

 of carbon dioxide it should give rise to adrenaline. It is of considerable 

 interest that on oxidation with tyrosinase a small amount of pressor 



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