INTERMEDIARY METABOLISM 



Structure between various substances. In spite of close chemical re- 

 semblances, the biological relationshi|)s of creatine to creatinine, of 

 phenylalanine to tyrosine, and of cholesterol to the Ijile acids and 

 steroid hormones have, until recently, remained hypothetical. The 

 balance type of experimentation with intact animals has, for various 

 reasons, failed to give conclusive answers to these problems. Even if 

 an oversupply in the diet of a suspected precursor leads to an increased 

 production of the correct reaction product, the conversion will remain 

 in doubt until the possibility of an indirect stimulating eflfect is excluded. 

 Balance experiments may be inconclusive because many biological 

 syntheses appear to proceed at rates which are, within limits, inde- 

 pendent of dietary variations. In such cases, the oversupply of a pre- 

 cursor will be without effect on the formation of the reaction product. 

 For instance, the immediate response to addition of excess creatine to 

 the diet is an increased excretion of creatine rather than of creatinine 

 (7). The conversion of creatine to creatinine becomes evident, how- 

 ever, by employing labeled creatine. When small amounts of creatine 

 containing N^'^ are fed to rats, the creatinine excreted contains isotopic 

 nitrogen (6). In this case, it is irrelevant whether or not creatinine is 

 increased in total amount; the presence of isotope is proof of the con- 

 version. 



A biochemical conversion may proceed independently of the 

 exogenous supply of the conversion product or of both conversion 

 product and precursor. When an essential dietary constituent is the 

 precursor, its concentration in the diet may regulate the extent of the 

 conversion, but it may be immaterial whether or not the conversion 

 product is supplied. Conversion of phenylalanine into tyrosine and 

 the methyl transfer from methionine in the synthesis of choline proceed 

 normally even when these products of conversion are amply provided 

 in the diet (15,26). 



If the precursor can be synthesized by the organism at an ade- 

 quate rate, its addition to the diet will likewise fail to increase produc- 

 tion of the conversion product. Interrelationships established with 

 the aid of labeled test substances (18,21,24), e. g., those existing between 

 the dispensable amino acids, proline, ornithine, and glutamic acid, 

 or between palmitic and stearic acids (19,22), could not be clarified 

 by quantitative methods because these reactions proceed independently 

 of the exogenous su{)ply of both precursor and reaction product. 



295 



