ISOTOPE TECHNIQUE 



equivalent amounts of ammonia does not give rise to a high concentia- 

 tion of N^^ in the excreted hippuric acid. This eUminates the pos- 

 sibility that the serine was deaminated and that the ammonia was 

 used to form glycine. The conversion of serine to glycine was confirmed 

 and the mechanism established by labeling the carboxyl group of serine 

 with C^^. Serine is converted to glycine by the splitting oflf of the j8- 

 carbon atom (unpublished experiments). 



A good example of the use of isotopes is to be found in the ex- 

 periments which led to establishment of the precursors of creatine. 

 The balance type of experimentation had completely failed to solve 

 this problem, and had not even been able to determine whether 

 creatine was biologically dehydrated to creatinine. Examination of 

 the structure of creatine suggested that glycine, arginine, and methio- 

 nine might be related to creatine. The feeding of labeled com- 

 pounds demonstrated that the COOH — CH2N — group of creatine 



was derived from glycine (5), the Cf group trom the amidine 



^ ■ \NHo 



group of arginine (5) and the methyl group froni methionine (47). 



In the last few years, a beginning has been made in the measure- 

 ment of the rates of the reactions involved in the synthesis of tissue 

 proteins. Feeding an animal with an amino acid labeled with N^^ 

 results in the incorporation of this nitrogen into most of the amino 

 acids of the proteins (31), a process which is of course dependent on the 

 rate of the formation of peptide bonds and the rate of transfer of 

 nitrogen from one amino acid to another. Measurement of the rate 

 of increase or decrease of isotope concentration of tissue proteins gives 

 a measure of the rate of formation of the proteins. Such studies reveal 

 a remarkable rate for protein .synthesis in rat livers; half of the protein 

 is degraded and resynthesized in six days (36). 



Not only are the "normal proteins" of animal tissues in a state 

 of dynamic equilibrium but also the antibodies, as shown with the aid 

 of isotopes in an actively immunized rabbit. The antibody protein 

 is broken down and newly synthesized even when the antibody titer ^ 

 is declining. The rate of decline of the antibody titer is not deter- 

 mined by an uncompensated destruction of the antibody protein but 

 rather is the result of two opposing reactions of which the rate of break- 

 down is faster than the rate of synthesis. The feeding of isotopic 



271 



