150 GROWTH PRINCIPLES AND THEORY 



TABLE 2 



EQ^UILIBRIUM CONCENTRATIONS OF POLYPEPTIDES 



After Schulz, 1950 



Degree of polymerization P Mole polymer per liter n* p 



2 10"'^ 



I o I o"^3 



I GO 1 0"692 



1000 IO-6993 



spending to protein — that is, with a polymerization well over 1,000 — is of a 

 fantastically low order of magnitude. 



I Hence the synthesis of high polymers needs energy which must be provided by 

 way of coupled reactions. In general, the energy yielded by cell respiration or 

 fermentation is stored in high-energy phosphate bonds, particularly of the 

 adenylic-acid system, and so available for non-spontaneous processes in the cell. 

 It is a fair inference, supported by considerable evidence from isotope experiments 

 with cell homogenates, that the energy for protein synthesis is provided by ATP 

 or related compounds, and that the ribonucleic acids localized in the microsomes 

 that line the endoplasmic reticulum, in some way act as templates for the pro- 

 duction of specific proteins characterized, in each particular case, by a specific 

 arrangement of amino acids. How protein synthesis is effectuated in detail is 

 unknown although there is a considerable number of proposed models {e.g. 

 Northrop, 1949; Caldwell and Hinshelwood, 1950; Haurowitz and Crampton, 

 1952; Dounce, 1953; Lipmann, 1954; Lockingen and Debusk, 1955; Zamecnik, 

 1958). Irrespective of the way in which protein synthesis takes place, the energetic 

 conditions can be indicated. 



According to the calculations mentioned above (G. V. Schulz, 1950, 1951) the 

 energy requirement for peptide bonds is — AG x 7 kcal/mole for a polymerization 

 /-> ^ 10,000. To the energy requirement of polymerization "chain entropy" has 

 to be added: Protein synthesis is not a mere polymerization but rather a formation 

 of chains of definite length and with a specific arrangement of amino acids within 

 the macromolecule. The additional amount of free energy which is necessary 

 for the synthesis of macromolecules of defined structure can be calculated from 

 Boltzmann's principle. For proteins consisting of ca. 20 different amino acids, 

 chain entropy results in an amount of additional — AG x 2kcal/mole. Since 

 free energy of the high energy phosphate bonds of ATP is a 1 2 kcal/mole, it is 

 suflficient to cover the energy requirements of protein synthesis, irrespective of 

 the mechanism of this process in detail. 



Isotope experiments with homogenates (Siekewitz, 1952; Zamecnik and Keller, 

 1954; Pollister, 1954; Ehrensvard, 1955; Zamecnik, 1958; and others) suggest at 

 least two steps in protein synthesis: one requiring energy furnished by oxidative 

 ' phosphorylation and taking place in the mitochondria ; and a second one requiring 

 less energy input, taking place in the microsomes, and yielding specific protein 

 chains. In other terms, it would appear that the first steps of protein synthesis 



