Sec. 25.5] MAJOR ORGANIC METABOLITES 517 



of carbon, has far from been exhausted, and particularly important future 

 applications should come with these isotopes used in doubly or multiply 

 labeled compounds. 



25.4. Oxygen. Oxygen has two rarer stable isotopes O 17 and O 18 that offer 

 considerable potentialities for biological application. So far, however, 

 only O 18 has been used in tracer work, and for very limited purposes. The 

 unstable species of longest half-life is O 15 (126 sec) ; this has not been employed 

 for tracer work and does not offer much promise. 



Although there have been several chemical tracer studies with O 18 , the 

 only biological tracer experiments so far reported are a study on photosyn- 

 thesis [09] in which it was shown that the oxygen released in this vital proc- 

 ess is derived from water and not from carbon dioxide, a brief investigation 

 of oxygen isotope exchange in animal respiration [04], and a study on sulfate 

 excretion in the rat [01]. Other biological studies with the oxygen isotopes 

 have been limited to analyses of their relative abundance in the oxygen 

 evolved in photosynthesis [06-8] and in bacterial metabolism [05]. In a 

 recent review on O 18 as a tracer isotope [03] the potentialities of this isotope 

 are discussed. 



There remains for the future, therefore, the vast field of intermediary 

 organic metabolism in which tracer work with oxygen isotopes may be 

 expected to reveal much fundamental information. 



25.5. Nitrogen. Nitrogen, which plays an essential role in the peptide 

 linkage of proteins, as well in the molecular configurations of nucleic acids, 

 many vitamins, and other fundamental components of living systems, has 

 two biologically useful isotopes: a short-lived unstable species N 13 (10.13 min 

 half-life) and a rarer stable species N 15 . 



N 13 may be made in the cyclotron by the reaction C 12 (d, n)N 13 , but it is not 

 a promising agent despite excellent cyclotron yields. It has had very 

 limited biological application as a tracer. The only studies so far reported 

 are ones supposedly demonstrating the fixation of nitrogen by a nonlegumi- 

 nous plant [N54] (however, subsequent work with N 15 [N17] has tended to 

 disprove this), and those of Jones [N35], who has employed N 13 in respiratory 

 gas-exchange studies. 



N 15 on the other hand has been extensively used as a tracer, particularly in 

 the study of the intermediary metabolism of amino acids and proteins. 

 Vennesland's recent review [N86] covers literature through 1947 in some 

 detail. 



An observation of particular interest has been the fact that proteins must 

 be highly labile molecules in which the peptide bonds are undergoing con- 

 tinual rupture and reclosure with freeing and exchange of amino groups. A 

 further important observation has been that, in so far as almost all the 

 essential amino acids are concerned, it is the carbon chain or ring rather 



