410 F. GROS 



direction; for instance, in the discovery of enzymes involved in the synthe- 

 sis of polynucleotides 1, 2 or in activating amino acids. 3 This is well illus- 

 trated in Chapter 37 on protein synthesis in in vitro systems. 



Now the time has come to wonder whether the enzymic reactions, the 

 existence of which has been demonstrated in vitro, represent the mechanisms 

 by which a cell actually synthesizes its essential constituents. As long as 

 this question remains unanswered it would be wise to consider the in vitro 

 synthesizing systems only as possible models for the cellular mechanisms 

 of biosynthesis. 



Thus, since in vitro studies on amino acid activation and the formation 

 of RNA amino acid complexes implicate these reactions as the initial step 

 in protein synthesis, a part of the present review will be concerned with 

 the question of whether amino acid activation operates in vivo in a manner 

 which makes it essential to the synthesis of protein by the cell. The review 

 will also deal with those problems of protein and nucleic acid biosynthesis 

 which have proved as yet to be too complex to be thoroughly studied in 

 in vitro systems. For instance, the problem of the role of nucleic acids as 

 the stable and specific templates for protein synthesis has been approached 

 in most cases by comparing the capacity of the cell to synthesize macro- 

 molecules under various conditions. Consequently a discussion of this prob- 

 lem will be particularly pertinent. 



For studies with intact cells, the bacterial cell is the one of choice: its 

 growth rate is very high; biochemical mutants with a precise metabolic 

 block can be easily selected; finally, enzyme induction which has proved to 

 be an important tool for studying the synthesis of specific proteins has been 

 thoroughly explored in bacteria. 



II. Organization of the Bacterial Cell 



Before considering mechanisms of protein biosynthesis, it is desirable to 

 survey briefly what is known about the chemical and cytochemical struc- 

 ture of the bacterial cell in the hope of discerning what cellular elements 

 are the important parameters in protein or nucleic acid synthesis. 



1. The Pool of "Free" Metabolites 



The cells of both prototrophic bacteria, which are able to synthesize all their 

 constituents from single nitrogen and carbon sources, and of heterotrophic bacteria, 

 always contain a pool of metabolites (amino acids, bases etc.) in the "free" form. 

 The size of this pool varies considerably with the specific nutritional requirements of 

 the strain and with the external concentration of the metabolites. The pool is larger 



1 M. Grunberg-Manago and S. Ochoa, J. Am. Chem. Soc. 77, 3165 (1955). 



2 A. Romberg, in "Chemical Basis of Heredity," p. 579. Johns Hopkins Press, 

 Baltimore, 1957. 



3 M. B. Hoagland, Biochim. et Biophys. Acta 16, 288 (1955). 



