MITOCHONDRIAL STRLCTURF. AND FUNCTION 91 



All the available evidence suggests and is in harmony with the concept that the 

 electron transfer particle is niatle up of limited numbers of protein components 

 which are linked to one another in a very precise manner by chemical bonds 

 which are strong enough to preserve the particle as a unit under physiological 

 conditions. The various components occur in stoichiometric proportions which are 

 as invariant as is the ratio of heme to globin in hemoglobin. The logical conse- 

 quences of this picture of the electron transfer particle lead us to some very difficult 

 problems which have yet to be fully resolved. If the component proteins of the 

 electron transfer chain are bonded to one another, then thermal collision has to 

 be excluded as a mechanism of electron transfer. What alternative mechanism can 

 account for the properties of the chain.? There appears to be a way out of this 

 dilemma, but I shall take the point up again when I have had the opportunity of 

 providing some background information. 



Perhaps the best way of explaining how we have set about acquiring informa- 

 tion on the structure of the electron transfer chain would be by way of the fol- 

 lowing schematic device. Let us represent the electron transfer chain as a linear 

 aggregate of proteins — A, B, C, D, E — linked together in the form A-B-C-D-E. 

 This would be the complete chain. By the application of appropriate reagents the 

 chain can be fragmented into smaller units such as A-B-C-D, A-B-C, and A-B. 

 The loss of any one component is accompanied by the loss of some enzymatic 

 property. From the composition and properties of the fragments one can deduce 

 the structure of the complete chain just as the structure of insulin has been de- 

 duced from the structure of the many peptides obtained by proteolytic or chemical 

 degradation of the parent protein. 



Nature has not obliged the biochemist with a simple linear chain. On the con- 

 trary, it appears to be one of bewildering complexity. But the argument still holds 

 — the difficulty is one of experimental execution, not of principle. Ways and means 

 have to be found to degrade the electron transport particle in a step-wise manner 

 without destroying activity. This has not been an easy assignment, and while we 

 have had a satisfying measure of success along these lines a vast area still remains 

 to be explored. 



It would not be easy for me to explain in a few words the many technical diffi- 

 culties which have for more than three decades frustrated efforts to deduce the 

 structure of the electron transport system. Suffice it to say that the technology for 

 the preparation and isolation of enzymatically active particles and the methodol- 

 ogy for the rapid assay, isolation and identification of particle-bound lipids had to 

 be developed before any substantial progress could be achieved. I might say par- 

 enthetically that lipid reagents such as higher alcohols, bile salts, and detergents 

 are the only reagents which have proved of value for the fragmentation ot the 

 electron transport particle. 



The conversion of mitochondria to subunits such as the electron transport par- 



