Cellular Metabolism 



83 



large cells the granules can be seen packed 

 into the centrifugal region. Concomitantly 

 the Q02 is depressed, apparently because the 

 enzyme has been concentrated to a point 

 where the uniformly distributed substrate 

 becomes limiting, even though the total 

 amounts of both substrate and enzyme per 

 cell are unchanged. Similar observations and 

 conclusions have been reported for silk worm 

 eggs (Wolsky, '50). 



The methods of cytochemistry have re- 

 vealed many suggestive localizations of en- 

 zymes in cells (cf. Bradfield, '50). The Go- 

 mori technique for alkaline phosphatase par- 

 ticularly has been examined with sufficient 

 thoroughness that we can rely on some, at 

 least, of the intracellular localizations it has 

 revealed; but again, correlated studies are 

 needed to show how these localizations aid in 

 controlling the functions of the cell. One in- 

 stance apparently demonstrating functional 

 change in location is the reported move- 

 ment of ATP of striated muscle from the A 

 bands, where it occurs during rest, to the 

 I bands during activity (cf. Caspersson and 

 Thorell, '42). 



To explain the very fast off-on effects that 

 occur in response to stimulation, it may be 

 necessary to seek out something more pre- 

 cise than simple isolation between enzyme 

 and substrate, which would apparently re- 

 quire diffusion of substance over a finite dis- 

 tance. Minor structiu-al alterations, convert- 

 ing an inhibited to an activated unit or vice 

 versa, might be a faster mechanism. Among 

 the few studies that appear to demonstrate 

 a possible mechanism for such a type of 

 control is that of Zamenhof and Chargaff 

 ('49) who found that DNase activity in cell- 

 free yeast preparations is increased with age. 

 The increase was shown to be due to the 

 destruction of an inhibitor which is bound 

 to the enzyme in fresh preparations. Prob- 

 ably the same association of enzyme and 

 inhibitor in the intact cell controls the 

 rate of breakdown of the cellular DNA. In 

 the same category we may perhaps place the 

 report of Barron and his associates ('48) that 

 the fixed sulfhydryl-containing enzymes in 

 cells are poised at a given state of oxida- 

 tion, and thus of activity, by the influence 

 of other sulfhydryl groups freely diffused in 

 the cytoplasm. 



One more possibility that should be men- 

 tioned in this section is that the activity 

 of an enzyme might be controlled simply 

 by being bound or not bovmd to structural 

 units. The evidence that the association of 

 enzyme molecules into formed structures in- 



fluences their activity has already been 

 considered. 



THE REGULATION OF METABOLISM IN 

 DEVELOPMENT 



That growth and differentiation must in- 

 volve enzyme production is axiomatic. Recog- 

 nition of this fact brings into sharp focus 

 the problems concerned with the mecha- 

 nisms by which the newly produced en- 

 zymes are integrated into the orderly scheme 

 of developmental events. In this section we 

 shall attempt to determine to what extent 

 the integrations of the embryonic period 

 may be explained in the same terms as have 

 proved useful in dealing with controlling 

 mechanisms in adult cells. No attempt will 

 be made to discuss the general energetics of 

 development, since this topic is covered in 

 Section VIII. 



It is necessary in this context first to dis- 

 tinguish between metabolism as an aspect 

 of development, and metabolism as a "cause" 

 of development. Failure to make this distinc- 

 tion has led to considerable confusion in the 

 past. The melange of events that make up 

 the life of the embryo is biochemical and 

 functional as well as structural. That the 

 chemogenetic events in some instances are 

 causally related to the morphogenetic events 

 is reasonable to assume; but attempts to 

 establish the causality are largely prema- 

 ture in the present state of our knowledge. 

 It seems to us that studies of regvilating 

 mechanisms in general embryonic biochem- 

 istry may provide the most fruitful clues to 

 the nature of the linkages between the chem- 

 istry and the morphology of embryos. 



Three special precautions must be kept in 

 mind in dealing with researches on en- 

 zymes in embryos. First, the assumption that 

 enzyme, cofactor, or substrate is not limiting 

 where one of the three is being dealt with 

 is less acceptable than in adult tissue, for ob- 

 vious reasons. Second, the small quantities 

 of embryonic tissue generally available, and 

 its relative instability, make negative results 

 more than usually suspect. The reported 

 demonstration that the chick embryo does not 

 have phosphorylative glycolysis, for example, 

 was completely refuted by the more careful 

 studies of Novikoff, Potter and LePage ('48). 

 Third, it must never be forgotten that an 

 embryo is in a continual state of differen- 

 tiation. Any circumstances or conditions es- 

 tablished for one stage, therefore, cannot be 

 assumed to hold for any other stage unless 

 specifically shown to do so. 



