CONTROL OF ENZYME ACTIVITIES IN D. DISCOIDEUM 

 DURING DEVELOPMENT 



Barbara Wright 



John Collins Warren Laboratory, Massachusetts General Hospital 

 Boston, Massachusetts 



I believe the usual concept of morphogenesis 

 includes a visible change in the form or struc- 

 ture of an organism. This implies a gradual 

 accumulation or redistribution of structural 

 material, such as connective tissue, bone or 

 cell wall polysaccharides, for example. This, 

 in turn, implies alterations in the activity of 

 enzymes responsible for the synthesis of these 

 materials. A number of possible mechanisms 

 for changing the activity of an enzyme appear 

 in Fig. 1. This figure summarizes various ways 

 in which the product characteristic of a par- 

 ticular differentiated cell might be made to 

 accumulate during development. The rate of 

 product accumulation could be enhanced by an 

 increased level of the enzyme, substrate, acti- 

 vator or RNA template used in the synthesis of 

 the enzyme. The accumulation of any of these 

 types of molecules, of course, implies nothing 

 with respect to the mechanism. The three possi- 

 bilities are a) an increased rate of synthesis, 

 b) a decreased rate of destruction or c) the ac- 

 tivation of a preformed inactive form of the 

 molecule. Thus, for each of the mechanisms 

 listed in the figure the problem is simply pushed 

 back to another level of analysis. 



Although our present state of knowledge 

 allows the discussion of these three possibilities 

 only with respect to enzyme levels as indicated 

 in the figure, levels of the other types of mole- 

 cules would be altered, also, by similar mecha- 

 nisms. Finally, it must be kept in mind that an 

 observed increase in level of any of these fac- 

 tors would be critical to the formation of a 

 product of differentiation only if it were already 

 limiting the process in the cell. Such informa- 

 tion is exceedingly difficult to obtain. Changing 

 levels of an enzyme or a substrate may only be 

 correlated with, and an indirect result of, the 



morphogenetic process observed and may be 

 due to causes quite unrelated to our naive and 

 prejudiced interpretation. The fact that DNA 

 and RNA play an important part, at some point, 

 in controlling the details of cellular differentia- 

 tion need not be documented. The question con- 

 cerns the time at which their action is necessary 

 relative to the unfolding of a particular develop- 

 mental process. 



DNA 



I 



RNA 



-^ PRODUCT OF DIFFERENTIATION 



Coenzyme, Activator 



Reaction may be stimulated by: 



1. Level of enzyme 



a) Increased synthesis (RNA and/or DNA activity) 



b) Decreased degradation (stabilization) 



c) Unmasking or activation (of preformed protein) 



2. Level of substrate 



3. Level of coenzyme, activator or inhibitor 



Fig. 1. 

 From Wright, Barbara E.: Control of Carbohydrate 



Synthesis in the Slime Mold. In Developmental and Meta- 

 bolic Control Mechanisms and Neoplasia (A Collection of 

 Papers Presented at the Nineteenth Annual Symposium 

 on Fundamental Cancer Research, 1965), p. 297. Balti- 

 more, The Williams and Wllkins Company, 1965. 



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