PRINCIPLES OF TRACER METHODOLOGY 37 



Some typical results have l)eeii summarized in Table 1-7 after calcula- 

 tion to a fractional basis. Space will not permit (iis(!ussion of compari- 

 sons but the interested reader may draw his own conclusions as to agree- 

 ment between investigators and species differences. 



Transfer Between Phases — Precursor Relationships. A common rate 

 problem is concerned with the transfer of a labeled substance from a phase 

 into which it is introduced into one or more phases in which the activity 

 may be measured. These rates are often used to give information on the 

 turnover rate and precursors of a substance normally present in the sys- 

 tem. The simplest method for determination of turnover by the dis- 

 appearance of a label has already been discussed (page 25). If it is nec- 

 essary to determine turnover rate from the appearance of a label in the 

 substance, then information must also be available on the time-activity 

 relationships of the immediate precursor of the substance. 



In some cases the specific activity of the precursor can be maintained 

 as a constant over the experimental period. Madden and Gould (84) 

 used this approach to determine the turnover rate of fibrinogen in the dog. 

 The animals were fed daily wdth sulfur-labeled methionine for about 3 

 weeks, at which time the specific activity of the fibrinogen reached an 

 equilibrium level. In this case the equation is 



2.3 log ^^^ = kt (1-33) 



where Seq= specific activity of fibrinogen at equilibrium 

 S = specific activity of fibrinogen at time t 

 k = constant = fraction renewed per unit time 



This equation can be derived by using the principles already set forth 

 and recalling that the specific activity of the precursor will be equal to 

 Seq. Thus the precursor does not need to be known, nor does its specific 

 activity need to be measured experimentally. Madden and Gould found 

 that the half-turnover time for fibrinogen in dogs averaged about 4 days, 

 and these values checked with observations made by the disappearance 

 method. It was of interest to note that S^Mabeled yeast gave just as 

 good results as methionine for the determination of turnover of pro- 

 teins under certain conditions. It was also pointed out that the reuti- 

 lization of labeled amino acids was decreased, in the disappearance 

 method, by feeding high levels of inert S-amino acids while following the 

 disappearance. 



The general precursor relationships have been developed by Zilversmit 

 et al. (68) and discussed in terms of the incorporation of a phosphate label 

 into phospholipid. It should be noted that there are two main problems, 

 the determination of turnover rate and identification of the precursor. 

 When labeled phosphate is injected into the blood stream, it becomes 



