OXIDASES, PEROXIDASES, AND CATALASE 75 



explanation that this activation is caused by a "deformation of the 

 electron shells of the oxygen atom" is little more than a clever means 

 of hiding our ignorance about a process which in biological import 

 may be likened to the primary reaction of carbon dioxide with 

 chlorophyll during photosynthesis. It is much easier to comprehend 

 the type of interaction represented by the oxidation of ferrocyto- 

 chrome by the ferri form of the respiratory ferment of Warburg. 

 This reaction must be determined, at least partly, by a difiFerence in 

 oxidation-reduction potential between the two iron compounds, al- 

 though it is not absolutely necessary that the normal potential of the 

 Warburg enzyme be considerably more positive than that of the 

 cytochrome. We know of instances where the reduced form of a 

 reversible system is oxidized partly by the oxidized form of a more 

 negative system, such as the methemoglobin formation by methylene 

 blue. The extent of such an interaction is governed by rigid thermo- 

 dynamic principles only in isolated and homogeneous systems where 

 no side reactions take place. In a living cell, where the ferrous 

 form of the respiratory enzyme is rapidly reoxidized by molecular 

 oxygen and the ferri form of cytochrome is rapidly reduced by 

 Hogness and Haas's "cytochrome reductase," the ratio of the various 

 forms, in the steady state of respiration, may differ considerably from 

 that in the isolated system. 



The catalytic power of hemins is, in the last analysis, a function 

 of the catalytic power of the central iron atom. The schema, traced 

 in Figure 1, illustrates how the highly complex and specialized 

 hemin protein enzymes stem from iron in its simplest form. In the 

 lowly iron sulfate we already encounter, in a rudimentary form, some 

 of the features which distinguish the oxidases, peroxidases, and 

 catalase. It is fascinating to watch the increase in catalytic activity 

 and the increasing degree of specialization that takes place as the 

 iron atom is riveted into compounds of increasingly complex struc- 

 ture. In many respects hemin occupies a central position in the 

 scheme. In its linkage to the porphyrin skeleton the iron atom 

 reaches a new level of catalytic activity. Under conditions where 

 simple iron salts decompose 10"^ moles of hydrogen peroxide, hemin 

 will split 10"^ moles, representing a thousandfold gain. That the 

 essential feature here is the iron-nitrogen-carbon bridge is indicated 

 by Warburg's classical experiments with charcoal prepared from 

 hemin, where this bridge apparently remains standing among the 

 ruins of the iron-porphyrin ring system and imparts a power to 

 oxidize cysteine and amino acids which is vastly superior to that 



