Enzyme theory

Adaptive Enzyme Theory. The aliesterases are largely found in the microsomes of rat liver cells (44). Recently Hart and Fouts (51,52, 67-69) have presented evidence that in vivo administration of chlordan or chemically related DDT stimulates the activity of hepatic microsomal drug-metabolizing enzymes, as evidenced by proliferation of smooth-surfaced endoplasmic reticulum (SER) which was first noted with phenobarbital. Several reviews of hepatic drug metabolism... 

Most of the work on skin biochemistry in relation to sulphur mustard burns was stimulated by the enzyme theory of vesication (Peters, 1936). It remains to be determined whether (a) injury is primarily dependent upon a direct reaction of the agents with one or a few specific and highly important proteins or other molecular species, or (b) there is a more or less random reaction of the vesicant with reactive groups of numerous proteins producing the observed pathological effects. 

Receptor theory is based on the classical Law of Mass Action as developed by Michaelis and Menten (20) for the study of enzyme catalysis. The extrapolation of classical enzyme theory to receptors is, however, an approximation. In an enzyme-substrate (ES) interaction, the substrate S undergoes an enzyme-catalyzed conversion to a product or products. Because of the equilibrium established, product accumulation has the ability to reverse the reaction process. Alternatively, the latter can be used in other cellular pathways and is thus removed from the equilibrium situation or can act as a feedback modulator (21) to alter the ES reaction either positively or negatively (Equation 10.2). 

The one-gene-one-enzyme theory also implied the correspondence in the ordered position of nucleotides in a gene with the position of amino acid in the protein encoded by that gene. This colinearity in the structure of a gene and that of a protein was demonstrated independently by Yanofsky et al. (1964) and by Sarabhai, et al. (1964), as discussed later in this chapter. 

The one-gene-one-enzyme theory generated the view that biochemical reactions are catalyzed individually by many enzymes one after another in a biochemical pathway. This view perpetuated through the development of molecular biology. 

On balance, the debranching-enzyme theory would appear to be unlikely. 

In 1941, George W. Beadle (1903-89) and Edward L. Tatum (1909-75), working at Stanford University, discovered that specific mutations of a bread mold, induced by X-rays or UV light, cause the mold to lose its ability to synthesize specific molecules such as pyridoxine (vitamin Bg). This led them to propose the one gene-one enzyme theory. At that time, the chemical nature of the gene was unknown, although proteins were the prime suspects. Beadle and Tatum would later share the... 

Seegers, W. Enzyme theory of blood clotting. Fed. Proc. 23, 749-756 (1964)... 

For diol dehydrase, a radical mechanism has been implicated from the observation that glycolaldehyde deactivates the enzyme. Theory suggests that this results because the radical H(HO)C CH(=0) formed by H atom abstraction is so stable that it will not abstract an H atom from HjCAdo to allow reformation of Co—CHjAdo. 

Brooks, S. P. J. Suelter, C. H. (1989). Practical aspects of coupling enzyme theory. Analytical Biochemistry, 176,1-14. 

---