On the Bigness of Enzymes 



DAVID RITTENBERC 



The action of enzymes seems to be dependent on two factors: one 

 geometric, the other energetic. The geometric factor is determined by 

 spatial relationships of the substrate and the corresponding enzyme. 

 Although it is beyond our capabilities to alter the basic structure of 

 an enzyme in any significant manner, it is relatively simple to prepare 

 and to test the interaction of a great number of variants of the natural 

 substrate with the enzyme. In this manner it has become clear that 

 specificity is geometrical in nature. It seems at present that all the 

 data can be explained if we assume that the substrate and the enzyme 

 have such a geometrical configuration as to permit the substrate 

 (generally the smaller of the two interacting particles) to approach 

 closely a portion of the enzyme molecule (the active site). 



Were we able to visualize the relative positions of the individual 

 atoms of the enzyme and of the substrate, we would see a mutual 

 complementarity preserved by non-specific Coulombic and van der 

 Waals forces. The Ogston hypothesis offers a simple explanation for 

 stereochemical specificity. 1 The same general concepts have been used 

 by Nachmansohn and Wilson 2 in their synthesis of all the isolated 

 facts concerning the interaction of choline esterase and its variously 

 modified substrates and inhibitors. 



Neither the substrate nor the products of the enzymatic reaction 

 should be bound too strongly to the enzyme since if either were the 

 reaction would cease owing to poisoning either by the substrate or the 

 products. Indeed, the explanation of the action of many catalytic 

 poisons seems to be the fact that they are strongly bound to the enzyme 

 surface, and that they do not permit access of the natural substrate 

 molecules, e.g., the inhibition of ferrous iron enzymes by carbon mon- 

 oxide. Since all enzymatic reaction takes place in water, the reaction 

 between the substrate and the enzyme should be formulated as: 



E±-(H 2 0)„ + S ^ E^CHjjOWS + 2/-H 2 (1) 



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