PROTEIN METABOLISM 491 



Replacement of Proteins 



When an animal is injured, the tissues involved must be repaired, 

 primarily a matter of protein synthesis. In addition, the inherent 

 thermodynamic instability of proteins in water implies that there may 

 be some continuing loss of protein which must be made good. Al- 

 though the biosynthetic mechanism of protein formation is difficult to 

 establish, the replacement of proteins is easily shown. 



Through studies with isotopes, it has been found that normal adult 

 animals continually replace their body proteins. It appears that the 

 various proteins are steadily decomposed and reassembled from the 

 bodily supply of amino acids. The rates of these exchange processes 

 vary with the type of protein and the animal species. Probably there 

 are variations with the age of the individual, his diet, and pathological 

 states as well. 



For example, when radioactive leucine or tyrosine is fed to adult 

 rats in nitrogen balance, radioactivity appears in the body proteins. 

 Administration of labeled amino acid for a comparatively short time 

 makes most radioactive those proteins which are being replaced most 

 rapidly. Likewise, if rats fed the radioactive amino acids for a definite 

 short time are then continued on diets with non-radioactive amino 

 acids, the radioactivity is lost quickly from the proteins replaced 

 rapidly and slowly from the more stable proteins. Studies have been 

 made of these rates of appearance and disappearance of radioactivity 

 from various proteins and tissues. 



For instance, in rats the proteins of plasma, liver, and other internal 

 organs are half-replaced every 6 to 7 days, a surprisingly short half- 

 life. Even the skeletal proteins have exchange half-lives of only 21 

 days on the average. One would expect variations in these groups, 

 but the important thing is that such studies indicate turnover of all 

 proteins of animals, even the matrix materials of bone. Man with a 

 longer life span also has longer half-lives for his proteins. Work with 

 abnormal concentrations of stable isotopes leads to the following 

 half-lives: 10 days for liver and serum proteins combined, and about 

 160 days for the combined proteins of brain, lung, skin, bone, and 

 muscle (the last predominating in quantity). 



Although it has been argued that the molecules affected by these 

 exchanges are not broken completely down to amino acids, it is clear 

 that such molecules must at least be partly degraded and then put 

 back together. A more serious j^roblem arises from reports that 

 sections of various non-growing animal tissues in laboratory cidtures 

 do not incorporate radioactive amino acids into their proteins. This 



