462 5. QUINONES 



polyphenols may be the result of complexes between the substances and 

 the iron of the enzyme (Frieden et al., 1961). In most instances one must 

 take into account complexes formed by the hydroquinones as well as the 

 quinones since both forms will be present. (4) Reaction with substrates or 

 cofactors. The inhibition of the hydrolysis of casein by papain was shown 

 to be due in part to the complexes fornied between the casein and hydro- 

 quinones, these complexes not being readily attacked by the enzyme 

 (Bahadur and Atreya, 1959). Certain thiol cofactors, such as lipoate or 

 coenzyme A, may be the primary sites of quinone action, although virtually 

 nothing about the reactivity of such cofactors is known. It was suggested 

 that the inhibition of arylamine acetyltransferase may be due to the ef- 

 fects of the quinones on coenzyme A (Guseva and Borikhina, 1958). (5) Pro- 

 duction of hydrogen peroxide. The oxidation of hydroquinones by Og often 

 forms H2O2, which could be the inhibitory agent. This mechanism was 

 postulated for the inactivation of pneumococcal transforming substance 

 (McCarty, 1945) and the inhibition of glycolysis in ascites cells (Piitter, 

 1963), but it could equally apply to certain enzymes. (6) Nonspecific bind- 

 ing through the aromatic rings. This would presumably be more important 

 for the polycyclic quinones, but might occur to some extent with the ben- 

 zoquinones, since nonquinoidal aromatic hydrocarbons often interact ap- 

 preciably with enzymes, as in the interesting study of Miles et al. (1963) 

 on the binding of benzene, naphthalene, and anthracene to chymotrypsin. 

 One would wish to see more controls run with nonquinoidal analogs of 

 the quinones being studied, so that the importance of the quinone groups 

 could be assessed. The inhibition of an enzyme by 1,4-naphthoquinone, 

 for example, cannot be immediately attributed to the quinone structure 

 unless related substances, such as a-naphthol or naphthalene, are shown 

 to be much less active. (7) Competition ivith quinonoid or polyphenolic sub- 

 strates (see page 467). 



Other mechanisms may be visualized in electron transport systems, 

 but for convenience the effects of quinones on such systems will be deferred 

 to a later section (see page 470). 



Oxidation of Enzyme Groups by Quinones 



Much attention was given to the redox state of enzyme groups in the 

 early studies, and it was observed that many enzymes, particularly protein- 

 ases such as papain, are catalytically active when the SH groups at or near 

 the active center are reduced but inactive when these groups are oxidized 

 (see page 11-636). Bersin and Logemann (1933) reported that papain is 

 inactivated by several oxidants, ^^-benzoquinone abolishing the activity at 

 1 mM. If a simple oxidation of SH groups were the sole result of treatment 

 of an enzyme with a quinone, activity should be restored by any agent 

 capable of reducing these groups to their original state, Hellerman and 



