Rate of Protein Synthesis in Man 191 



of the living cell owe their secular stability not to an absence 

 of reactions nor to existence of a time independent equilibrium 

 state, but because they are a part of a kinetically stationary 

 state. It is important that we clearly differentiate between 

 an equilibrium and a steady state (Burton, 1939; Bertalanffy, 

 1950; Denbigh, Hicks and Page, 1948). A system at equili- 

 brium is a closed one; material neither enters nor leaves and 

 the state is determined by thermodynamic quantities. A 

 system in a stationary state is an open system ; materials 

 enter and leave and the state is determined by kinetic factors. 

 I have previously indicated the advantages which accrue to a 

 living cell from this form of organization (Rittenberg, 1949). 



These general considerations indicate that kinetic data are 

 required if we are ever to understand the problem of the living 

 cell. Some years ago Shemin and I (Shemin and Rittenberg, 

 1944) attempted to measure the rate of protein formation in 

 the rat. We found that the liver proteins of this animal were 

 being regenerated with a half time no greater than 8 days. 

 Even faster was the regeneration rate of glutathione ( Waelsch 

 and Rittenberg, 1942). The half time of this tripeptide is 

 less than 4 hours. 



Studies in our laboratory on the rate of formation of the 

 human plasma proteins indicate that they have a half time 

 of about 10 days. In none of the experiments reported above 

 was it possible to determine the metabolic activity of the 

 great bulk of the tissue proteins, the muscle. Recently a 

 method has been developed (Sprinson and Rittenberg, 1949) 

 by which the absolute rate of protein synthesis in an intact 

 animal could be estimated. The assumption underlying this 

 method is that a dietary amino-acid is either used for protein 

 synthesis or is oxidized and its nitrogen excreted. This is 

 not true in all details, for we know that dietary nitrogen 

 can be used for the synthesis of nitrogenous compounds 

 other than protein. Quantitatively these are but minor side 

 reactions, and we have ignored them. The excretion of 

 dietary nitrogen will thus reflect the rate of protein synthesis. 

 The more rapid the synthesis, the less dietary nitrogen will 



