Rate of Protein Synthesis in Man 201 



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DISCUSSION 



Neuberger: We have been worried for the last few years by problems 

 similar to those Dr. Rittenberg has indicated about assmnptions made 

 in the interpretation of experiments on nitrogen metabolism and turn- 

 over rates, in this case not in man but in the rat. We, of course, realized 

 that one has to make certain simplifying assumptions to get a system 

 which is susceptible to mathematical treatment. However, there were 

 two points in the treatment of Dr. Rittenberg and Dr. Sprinson which 

 worried us slightly and I would just like to put them forward for 

 discussion. 



The first assumption made is that the metabolic pool is physically 

 essentially homogeneous. For example, if glycine is used for synthesis 

 of protein in the liver and in muscle, it is assumed that this glycine is 

 rapidly equilibrated between muscle and liver. I think that this is 

 unlikely to be quantitatively correct because the penetration of amino 

 acids into certain tissues like muscle and to a much greater extent into 

 the cells of the central nervous system, is relatively slow. If the 

 rate of protein synthesis in the liver is of the same order of magnitude 

 as the rate of penetration of glycine from the intracellular space of 

 the liver to the intracellular space of the muscle, you may get a steady 

 state, in which the isotope concentrations are different, and the assump- 

 tion of a homogeneous compartment falls to the ground. Further, if, 

 for instance, the degradation of glycine concerns mainly the glycine in 

 the liver, and if this liver glycine is not in equilibrium with muscle 

 glycine, you again may get a considerable error by assuming that the 

 urinary nitrogen is derived from a homogeneous pool in the body. 



The other point is that, if you give labelled nitrogen in any form, 

 either in the form of ammonia or of glycine, one makes the assumption 

 that this labelled nitrogen gets quickly distributed over other nitro- 

 geneous compounds. I am not quite sure whether this is an assumption 

 which has to be made, but if it is so, then how far is this assumption 

 correct? There are these two points where lack of homogeneity might 

 be quite serious and I am just wondering whether it wouldn't be possible 

 to assume that you have a series of compartments; this of course makes 

 the mathematical treatment extremely complicated, but one might 

 get somewhat nearer the true state of affairs. I'm just putting this 

 forward with some hesitation as points for discussion. 



Rittenberg: The point which Dr. Neuberger has raised of course 

 has troubled us greatly. I trust we are in agreement that at the present 

 stage of matters it is not worth while to be too fussy about little points, 

 because you first want to get the broad outline of the matter straightened 

 out. The two points you have raised are indeed very important ones. 



