ELECTRON TRANSPORT 657 



ELECTRON TRANSPORT AND OXIDATIVE 

 PHOSPHORYLATION 



Several oxidizing enzyme systems are inhibited by arsenicals and the 

 question of the site of action in the electron transport sequence will be 

 briefly considered. The original idea that arsenite acts like cyanide was 

 proved to be incorrect (see page 598), and it is now generally accepted 

 that the inhibition is exerted mainly, if not entirely, on the dehydrogenase 

 component, and more specifically at the substrate site, unless high concen- 

 trations are used. The evidence for this is of several different types. (1) 

 Failure to inhibit significantly the more distal portions of the electron transport 

 sequence. Thus the oxidations of cytochrome c, indophenol dyes, and 

 p-phenylenediamine are depressed only when higher concentrations of 

 the arsenicals are employed (Szent-Gyorgyi, 1930; Cohen and Gerard, 

 1937; Mahler et ciL, 1954; Aldridge and Cremer, 1955). (2) Inhibition of 

 the reduction of various acceptors. It has been demonstrated in many systems 

 that the inhibitions of the reduction of methylene blue, phenazines, cyto- 

 chrome c, and other acceptors are quite comparable to the inhibitions 

 exerted on the entire system (Banga et al., 1931; Das, 1937 a; Peters et al., 

 1946; Slater, 1949; Mackler et al, 1954; Mahler et al, 1954; Thorn, 1959). 

 (3) Protection by substrates or inhibitors competitive with substrates. Some 

 instances of protection have been discussed (page 648) and here we shall 

 note only additional work on the succinate oxidase system (Barron and 

 Singer, 1945; Bergstermann and Mangier, 1948; Stoppani and Brignone, 

 1957). The relative sensitivities of many dehydrogenases do not imply 

 that all dehydrogenases are readily inhibited, some, such as the malate 

 dehydrogenase, being quite resistant, nor that other steps in the electron 

 transport chain cannot be inhibited when the arsenical concentration is 

 raised sufficiently. As in all cases, attention must be paid to using the proj^er 

 concentration if a selective action is desired. It should be borne in mind 

 that trivalent arsenicals can occasionally directly reduce components of 

 the electron transport system. Legge (1954) showed that arsenite reduces 

 cytochrome c in certain bacteria and such an action might account for 

 some of the stimulations observed with the arsenicals. One factor which 

 may be involved in the susceptibility of dehydrogenases in vivo is the lipid 

 component and the thiols which form complexes with the enzyme, as shown 

 by Jurtshuk et al. (1963) for the /5-hydroxybutyrate: NAD oxidoreductase 

 from heart mitochondria, the system being activated by lecithin and thiols. 

 The dimercaprol complex is sensitive to arsenite whereas the cysteine 

 complex is not. We do not know what the natural apodehydrogenase- 

 lipid-thiol is. 



The results on oxidative phosphorylation have been variable, as is 

 common with the SH reagents, and it is likely that the effects of the arsen- 

 icals on the P:0 ratio depend not only on the preparation used but also 



