OXIDATION AND REDUCTION 



level: some of the enzymes can be prepared as pure crystalline entities, 

 and their composition and activity can be examined. Since the first 

 stages in their discovery by Warburg, a vast amount of knowledge has 

 been accumulated which, on the one hand, demonstrates the highly 

 complex nature of the problem and, on the other, shows that certain 

 recognizable features are shared by these enzymes: they are proteins 

 attached to prosthetic groups. The proteins are all specific and not 

 identical with those otherwise occurring in the organism. But the 

 chemical mechanism of the action of these enzymes is not yet worked 

 out, at least to an extent comparable to that given in the simple example 

 of iron catalysis in the oxidation of cysteine. 



It is quite natural that enzyme chemists have, thus far, been 

 occupied with the discovery of many kinds of enzymes, the ingenious 

 methods of preparing them, and the measurement of their activity. 

 But at this point we must inquire into the chemical mechanism by 

 which they work; and here only a few speculations can be brought 

 up. One simple suggestion is this: if it is true that the sluggishness 

 of an oxidation process is caused by the instability (in its thermo- 

 dynamic sense) of the free radical through which the over-all oxidation 

 has to pass, then the function of the enzyme may be that of increasing 

 the stability of the radical, in other words, that of increasing the con- 

 centration of the radical which can exist in equilibrium with the re- 

 duced and the oxidized state of the substrate. The substrate com- 

 bines, reversibly, with the enzyme, and the "semiquinone formation 

 constant" of the enzyme-substrate compound may be greater than that 

 of the uncombined compound. We may make another suggestion. 

 Let us suppose that the enzyme can combine not only with the sub- 

 strate to be oxidized but also with the oxidizing agent. For example, 

 methylene blue can oxidize succinic acid to fumaric acid in the presence 

 of the enzyme called succinodehydrogenase. Suppose this enzyme can 

 combine with both succinic acid and methylene blue. The specific 

 structure of the enzyme brings about a definite spatial orientation and 

 juxtaposition of fumaric acid and methylene blue. When a mole- 

 cule of one of these two substances collides with a molecule of the other 

 in a solution, the chance of an electron transfer during the short time 

 of collision is nil; but when these two molecules are held close together 

 in appropriate juxtaposition and orientation with respect to each other, 

 they remain in this spatial arrangement for a long time, during which 



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