INHIBITION OF ENZYMES 



445 



globulin antigen elicited antibodies in the rabbit and these were shown to 

 be specific for 1,2-naphthoquinone. The cutaneous anaphylaxis produced 

 by 1,2-naphthoquinone is due to an initial rapid combination with serum 

 proteins. Quinones may alter protein structure by forming interchain or 

 interprotein links: 



— S 



It is not known how important this is in enzyme work, but certain ef- 

 fects on cells could well be mediated through the formation of such links 

 in the membrane. This subject has been studied with respect to structural 

 proteins, such as collagen and keratin, because of its importance in the 

 tanning industry. Another factor is the autoxidation and polymerization 

 of the quinones, since these polymers are bound to the proteins; this is 

 quite dependent on the pH, increasing from pH 7 to pH 8, below pH 7 

 only the monomeric quinone being bound (Stecker and Highberger, 1942; 

 Theis, 1945). Cross-linking by quinones in keratin fibers was demonstrated 

 by Stoves (1943) by load-extension curves, and several have suggested that 

 cuticular hardening in insects is brought about by o-quinones serving as 

 interfibrillar links. Since most of this work has been done with reasonably 

 high concentrations of quinones (i. e., mostly over 5 mM), it is difficult 

 to predict what would happen at the concentrations generally used in 

 metabolic studies. 



INHIBITION OF ENZYMES 



A variety of enzymes are quite potently inhibited by the quinones but 

 this by no means reflects a single common mechanism of action. Even 

 among the simpler quinones we find different patterns of specificity. Some 

 of the more important results are summarized in Table 5-2, and anyone 

 interested in the relation between structure and action will find many in- 

 triguing problems there. The more common mechanisms by which the qui- 

 nones inhibit enzymes are as follows. (1) Oxidation of enzyme groups (see 

 the next section). (2) Reaction with enzyme SH groups (see page 463). 

 (3) Complexing with metal ions. The formation of complexes between various 

 quinones and the copper of tyrosinase has been demonstrated using Cu^* 

 and an ion-exchange resin (Arthur and McLemore, 1956). The o-quinones 

 form more stable complexes than the p-quinones, and this is probably 

 generally true. The inhibition of tryptophan pyrrolase by quinones and 



