EFFECTS ON ELECTRON TRANSPORT SYSTEMS 475 



some extent in this way. The fundamental mechanism may fall into one 

 of the above categories but is at present unknown. 



Examples of the Inhibition of Electron Transport 



An apparent paradox exists with respect to bacterial NAD (P)H: nitrate 

 oxidoreductase. Wainwright (1955) found a nitrate reductase from E. coli 

 to require menadione, or a related naphthoquinone, for activity, but Sa- 

 dana and McElroy (1957) reported a similar enzyme from Achromohacter 

 fischeri to be completely inhibited by 0.03 mM menadione. The discrepancy 

 may be due simply to the fact that the electron transport systems may be 

 quite different in the two organisms, but may also be due to the different 

 electron donors used. Wainwright used methylene blue while Sadana and 

 McElroy used NADH. When the latter workers used reduced benzylviologen 

 as a donor, no inhibition by menadione was observed. Thus it may be that 

 methylene blue feeds into a menadione-requiring region of the system, while 

 a region readily blocked by menadione may exist between NADH and the 

 site at which the dyes donate electrons. This at least illustrates the impor- 

 tance of considering the electron donors and acceptors used, and serves as 

 a warning against carrying over results obtained on artificial systems to 

 intact systems as they occur in the cell. 



Certain analogs of coenzyme Q inhibit quite potently the oxidation of 

 succinate in liver mitochondria. Qq, 6-Cl-Qo, and 6-Br-Qo* inhibit around 

 75% at concentrations near 0.12 mM, while Q^, Qa, and Q3 slightly stimu- 

 late the rate of oxidation (Jacobs and Crane, 1960). In acetone-extracted 

 mitochondria, which have lost their succinate cytochrome c reductase ac- 

 tivity, coenzyme Q analogs inhibit the restoration of activity induced by 

 adding the natural quinones (F. L. Crane, 1960). Thus diethoxy-Qio is 

 inhibitory and this inhibition is antagonized by Qjq, but other inhibitions, 

 such as that produced by lapachol, cannot be reversed by Q^q, so that the 

 latter inhibitions must be at a different site in the sequence. The reduction 

 of cytochrome c by succinate is inhibited 82% by 0.02 mM 6-Br-Qo and 

 this is prevented by cysteine or glutathione (Smith and Lester, 1961). 

 Both these workers and Jacobs and Crane (1960) feel that reactions of 

 these quinones with SH groups may be important in their actions. The 

 inhibition of succinate oxidation by lapachol and hydrolapachol is released 

 by 2,4-dinitrophenol, and this was thought to be due to a dissociation of 

 the inhibitor complexes (Rowland, 1963 b), but possibly the un coupler 

 shifts the electron flow to a pathway insensitive to these naphthoquinones. 



Horseradish peroxidase catalyzes the oxidation of menadiol, reduced 

 vitamin K^, and QjoHg, and this is inhibited by various quinones (see 



* Q„ represents coenzyme Q (ubiquinone) Avith n indicating the number of iso- 

 prenoid units (see formula on page 471). 



