Evolution of Enzymes 209 



iron porphyrin, or haem, as it is incorporated into a protein, surrounded by two 

 more co-ordinating groups of the protein to form catalase. The progressive 

 increase in catalytic ability is from lO"^ for the aqueous ferric ion to io~2 for 

 the haem to lo^ for the complete enzyme. These are definitions of the catalytic 

 function of the iron for the reaction involving the decomposition of hydrogen 

 peroxide. However, we know that the iron has other functions, as well, most of 

 which involve oxidation or reduction. For example, even catalase itself can func- 

 tion as a peroxidase, using hydrogen peroxide to oxidize organic substrates, pro- 

 vided the hydrogen peroxide is sufficiently dilute. Undoubtedly, the iron is also 

 involved in what we now recognize as oxidative phosphorylation, that is, the 

 conversion of the energy liberated upon the passage of an electron from a highly 

 reducing potential to an oxidizing agent, such as oxygen or other material, with 

 the concomitant storage of some of that energy in the form of unstable (pyro- 

 phosphate) linkages which may later be used for other purposes. 



In order to convert the rudimentary catalj^c functions which exist in all the 

 elements and their simple compounds into the highly efficient ones that we now 

 recognize as enzymes, we must introduce two additional ideas, one from the realm 

 of chemistry and the other from the realm of genetics, both of which, however, 

 coiild be considered as manifestations of exactly the same phenomenon. The first 

 of these, from the realm of chemistry, is the idea of autocatalysis, that is, the 

 basic notion that the product of a reaction may itself be a catalyst for the con- 

 version of precursors into itself. This is a very common phenomenon in chemistry 

 and perhaps is best illustrated in one of the simplest cases, namely, the reaction 

 of molecular hydrogen with cupric ion. This reaction leads thermodynamically 

 to the formation of cuprous ion and water. It so happens that the reaction of 

 molecular hydrogen with cupric ion, although thermodynamically possible, is an 

 extremely slow one without catalysis. However, the product of this reaction, 

 that is, cuprous ion, is an extremely good catalyst for the reaction between 

 hydrogen and cupric ion. Therefore, one can imagine, and indeed we have 

 experimentally realized this long ago, a system consisting of molecular hydrogen 

 and cupric ion which remain in this form for some period of time. However, 

 should either a very slow noncatalytic reduction lead to cuprous ion, or should 

 some random electron transfer lead to the formation of an appreciable nvmiber 

 of cuprous ions in the mixture, then immediately the entire reaction mixture 

 goes over to the more stable system consisting of cuprous ion. 



The other notion which we would like to introduce is the one developed by the 

 geneticist Horowitz. He suggested that the very complex series of reactions which 

 we are now finding to be responsible for the synthesis of most of our existing 

 biological material could have developed in a backward manner, beginning with 

 the completely heterotrophic organism. He postulated that the first living things, 

 complete heterotrophs, had available to them all possible precursors for their 

 own duplication, and that their only function was to bring these together to 

 produce themselves. One can then visualize a process in which at first one 

 essential constituent of the mixture is depleted. Then, the particular organiza- 

 tional unit which foimd a way of manufacturing the depleted item from remain- 

 ing molecules will, of course, survive, whereas those imits which are unable to 



14 



