2 INTERMEDIARY METABOLISM AND GROWTH I 



map of any cell differs from this general map in that certain areas of the map are 

 deleted and certain arrows are interrupted. For example, the reactions leading to 

 the synthesis of thyroxine and of steroid hormones take place in endocrine tissues but 

 not in the other tissues of the animal; the steps leading to the synthesis of the amino 

 acids, arginine and tyrosine, take place readily in liver cells but only to a very limited 

 degree in most of the other cells of the body. The mold, Meurospora, synthesizes lysine, 

 by the aminoadipic acid pathway whereas many bacteria synthesize this amino acid 

 by the diaminopimelic acid pathway, and some microorganisms and also mammalian 

 cells cannot synthesize lysine at all. In other words, cells also differ from one 

 another in that, i) a particular metabolic pathway is quantitatively more important 

 in one type of cell, and 2) alternative solutions may be found for the same meta- 

 bolic problem, as in the case of synthesis of lysine. 



Since growth is an endergonic process, the metabolic activities of cells must 

 be organized in such a way that the free energy derived from catabolic processes 

 is available for the growth process. In this chapter, we will first examine the varied 

 biochemical processes as a result of which free energy becomes available for cel- 

 lular anabolism; secondly, the coupling devices for shunting the free energy into 

 the growth process will be discussed; and thirdly, we will examine the chemical 

 processes which lead to the synthesis of the building blocks of protoplasm. 



The subject of intermediary metabolism deals with one of the most dynamic 

 branches of biochemistry. Thus, the research of tomorrow will undoubtedly 

 render obsolete some of the tentative formulations of today. However, we may 

 confidently build upon the solid foundation of factual knowledge which has been 

 amassed. 



Much of the information discussed in this chapter has been summarized recently 

 in a series of monographs, on intermediary metabolism. These include Chemical 

 Pathways of Metabolism (Greenberg, 1954), and a number of Symposia held 

 imder the auspices of Johns Hopkins University (McElroy and Glass, 1 951-1952, 

 ^953' 1 954) ''955)- Excellent reviews on intermediary metabolism have also ap- 

 peared in the annual volumes of Advances in Enzymology and the Annual Reviews of 

 Biochemistry. 



II. ENERGY YIELDING PROCESSES 



A. Introduction 



It is convenient to begin a discussion of cellular metabolism by directing attention 

 to the biochemical secjuences referred to as glycolysis and the tricarboxylic acid 

 cycle. These chemical reactions catalyzed by enzymes may properly be considered 

 the backbone of the chemical activities of the cell and are shown in detail in Fig. i. 

 It is to be noted that certain metabolites, namely, glucose, glycer aldehyde phosphate, 

 ribose phosphate, acetyl-CoA, pyruvate, phosphoenolpyruvate, oxalacetic acid, a-ketoglutaric 

 acid, and succinyl-CoA, have been emphasized as key intermediates. Each may 

 serve as the substrate for several different enzymatic reactions. For example, 

 pyruvate may be reduced by a dehydrogenase to lactate, carboxylated to oxal- 

 acetate, aminated by a transaminase to alanine, or it may be oxidatively decar- 



