Chapter 3 



CONTROL SYSTEMS AND RHYTHMIC PHENOMENA 



IN CELLS 



Molecular Control Mechanisms 



It is the recent discoveries concerning the detailed biochemical operation of 

 cellular coding and control mechanisms which has brought into biology an 

 unprecedented excitement and glamour, and the possibility of laying a firm 

 and unifying foundation for the understanding of biological processes in cells. 

 The most fundamental result of the control studies is the demonstration that 

 highly specific control mechanisms operate by means of feed-back devices to 

 regulate the concentrations of macromolecular species and their activities. 

 The feed-back signals for control of macromolecular activity are usually the 

 small, rapidly diffusing molecules of what has been termed the metabolic 

 system. The causal chain from DNA to RNA to protein to metabolite has 

 been closed by the demonstration that metabolites act upon gene activities in 

 a very precise manner. These metabolites act with a high degree of specificity 

 upon particular genetic loci, so that changes of state in cells are the result of 

 interactions of a much more detailed kind than the general competitive inter- 

 actions which were previously believed to underly the regulation of cellular 

 activities. Causal control loops of this kind also appear to exist with a shorter 

 pathway than that from DNA to metabolite and back to DNA. It is possible 

 that feed-back inhibition may occur between metabolites and messenger 

 RNA of ribosomes, while inhibition of enzyme action by products has been 

 known for some time. What is new in the effects of metabolite on enzyme 

 action is the discovery that a molecule which bears no stereochemical relation- 

 ship to the normal substrate of an enzyme can nevertheless inhibit its activity 

 (Gerhardt and Pardee, 1962). 



Thus there are three levels at which metabolites can alter the activities of 

 macromolecules by specific interaction : at the DNA level, affecting either DNA 

 or RNA synthesis ; at the messenger RNA level, affecting protein synthesis ; and 

 at the protein level, affecting either enzyme activity or some other activity of 

 proteins, such as contractability. In the present work our attention will be 

 directed largely to the first level of control, that of gene activities. The effects 

 of metabolites on enzymes and other macromolecules belong properly within 

 the time-scale of the metabolic system, as we argued in the last chapter. 

 However, it is true that the steady state of the metabolic system is affected by 

 interactions of metabolites with macromolecules, so that whenever metabolic 

 steady states are calculated these effects must be included. This question will 

 arise in the next chapter. 



The establishment of specific, closed causal loops in the biochemical 



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