INHIBITION OF ENZYMES 467 



would abolish the inhibition. This is borne out in that dihydroxy-1,4- 

 naphthoquinone and 3-hydroxymenadione have relatively little inhibitory 

 activity against succinate dehydrogenase (Herz, 1954 b), and the latter 

 compound has little effect on pyruvate decarboxylase (Kuhn and Beinert, 

 1947). On the other hand, 2,3-dichloro-l,4-napthoquinone is usually even 

 more inhibitory than the parent naphthoquinone, which may be correlated 

 with the fact that chlorination actually increases 1,4 addition of SH groups. 

 The effects of various groups substituted in the 2-position of 1,4-naphtho- 

 quinone on the inhibition of pyruvate decarboxylase are very marked 

 (Foote et al., 1949) and cannot be correlated entirely with change in the 

 values of £'o'. That 2-mercapto-l,4-naphthoquinone is some 145 times more 

 inhibitory than 2-hydroxy-l,4-naphthoquinone is interesting. The low in- 

 hibitory activity of lawsone cannot be attributed to its tautomerism with 

 the 1,2-naphthoquinone structure since 1,2-naphthoquinone is as inhibitory 

 as 1,4-naphthoquinone. The introduction of a methyl group into the 2- 

 position to give menadione usually reduces the activity somewhat, as is 

 seen particularly well with urease (Schopfer and Grob, 1949 b), but a chlorine 

 group increases the inhibitory potency about 5 times, these changes possibly 

 being due to the inductive effects of these two groups with respect to making 

 the 3-position reactive with SH groups. 



Formal Nature and Kinetics of Inhibitions 



In a surprising number of instances the inhibition by quinones has been 

 found to be formally competitive; examples are carbonic anhydrase (Chiba 

 et al., 1954 b) and the phosphate-activated renal glutaminase (Sayre and 

 Roberts, 1958). In the latter case, p-benzoquinone apparently competes 

 with the phosphate and not the substrate. Some enzymes are competitively 

 inhibited by hydroquinones, for example catechol oxidase (Kuttner and 

 Wagreich, 1953) and D-amino acid oxidase (Frisell et al., 1956). A com- 

 petitive relationship for catechol oxidase is of course not unexpected, and 

 the inhibitions produced with certain enzymes acting on phenolic sub- 

 stances or requiring such substances for activity, such as /5-glucosidase 

 (acting on arbutin, salicin, and related glucosides), NADHiHgOa oxido- 

 reductase, and homogentisate oxidase, are probably competitive. 1,2- 

 Naphthoquinone-4-sulfonate competitively inhibits both dopa decarbo- 

 xylase (Hartman et al., 1955) and L-glutamate decarboxylase (Roberts 

 and Simonsen, 1963), but this may be more related to the sulfonate group. 

 The inhibition of succinate dehydrogenase must be dynamically competi- 

 tive, since succinate protects the enzyme, but would be noncompetitive 

 under equilibrium conditions (Potter and DuBois, 1943). Indeed, Red- 

 fearn and Whittaker (1962) reported noncompetitive inhibition by two 

 p-benzoquinones of a heart succinate dehydrogenase preparation using 

 methylene blue as an acceptor and ubiquinone analogs as mediators. 



