364 VIII. HEMATIN ENZYMES, I. CYTOCHROME SYSTEM 



ferric form of the enzyme reacts with cyanide. According to this 

 view the catalytic cycle of the respiratory ferment and the action of 

 inhibitors on it can be written diagrammatically as follows: 



O2 

 Fe'+ CO ^ Fe"-+ ;:^ Fe"-+ O, 



CO I I 



I i ^ CN- 



Substrate Fe'^ ^ Fe'+ CN" 



The substrate, as will be seen below, is generally cytochrome c. 



If this is correct the enzyme behaves toward cyanide as does hemo- 

 globin. It has been shown in Chapter VI, Section 2.2.5., that hemo- 

 globin forms only a highly unstable compound with cyanide, while 

 hemoglobin forms a very stable one. We have discussed in Chapter 

 V (Section 6.3.), however, that this is by no means the general 

 behavior of heme compounds to cyanide. Keilin and Hartree {14-93) 

 have, indeed, shown that cytochrome as reacts with cyanide both in 

 the ferrous and ferric form (cf. Section 3.6.5.), and the experiments 

 of Tamiya and Kubo {2733) on the influence of cyanide on the 

 distribution constant, K, of the respiratory ferment between oxygen 

 and carbon monoxide are also not in agreement with Warburg's 

 conception. Cyanide ferroporphyrins are autoxidizable, and cyanide 

 ferriporphyrins are reduced only slowly by nascent hydrogen (Barron 

 and Hastings, 186), although cyanide combines more firmly with 

 ferroporphyrin than with ferriporphyrin. It is therefore likely that 

 the inhibition of the respiratory ferment by cyanide must be ex- 

 plained kinetically, not thermodynamically. 



Carbylamine does not inhibit the respiration of yeast (2918). 

 Keilin {lJf.82) found that azide inhibited the respiration of yeast only 

 below /)H 6.7, not at pH 7.5, while it inhibited cytochrome oxidase 

 at both pW values. Keilin and Hartree (1498) have recently observed 

 that red cells are permeable to azide at low />H values, but are 

 impermeable at pH 7.5. This probably holds also for other cells 

 and explains the difference between the azide inhibition of isolated 

 cytochrome oxidase and intact cell respiration.* The probable identity 

 of cytochrome oxidase with Warburg's respiratory ferment will be 

 discussed under Section 3.6.5. Hydroxylamine, which also inhibits 

 cytochrome oxidase, exerts marked inhibition on the respiration of 

 kidney slices, but very little on that of testis (289). 



* (/., however, Stannard and Horecker {l-Hlh). 



