470 C. F. Strittmatter 



of liver is concentrated most markedly in this fraction (Hogeboom, 1949; 

 Strittmatter and Ball, 1954). As noted earlier, the microsomal cytochrome 

 and its reductases comprise an efficient antimycin A-insensitive system that 

 could account for a quantitatively important flow of electrons from DPNH 

 (or TPNH) or other donors. However, the question arises as to whether this 

 system functions biologically, and if so, what substances serve as electron 

 acceptors physiologically. 



Terminal Electron Transport 



The microsomal cytochrome might serve as a link in terminal electron 

 transport to oxygen either directly or via mediators. 



The autoxidizability of microsomal cytochrome may suggest a role as a 

 terminal oxidase, but the low rate of autoxidation militates against any major 

 quantitative signihcance of such a role. The turnover number of purified 

 rabbit liver microsomal cytochrome with oxygen as electron acceptor is of 

 the order of 1/min, in contrast with the very rapid rate of turnover with 

 cytochrome c as acceptor (Strittmatter, unpublished work). A hmiting value 

 for the rate of autoxidation physiologically is suggested by the report that 

 the turnover numbers for aerobic reoxidation of microsomal cytochrome in 

 intact liver microsomes in the presence and absence of CN~ are 1-2 and 

 3-6/min respectively (Chance and Williams, 1954). Thus the DPNH oxidase 

 activity of liver microsomes is very low compared to the DPNH cytochrome 

 c reductase capacity of these particles or the DPNH oxidase activity of the 

 mitochondria (Strittmatter and Ball, 1954; Hogeboom, 1949; Hogeboom, 

 Claude and Hotchkiss, 1946). Nevertheless, a terminal oxidase role has been 

 postulated for cytochrome b^ in systems with low rates of oxygen consump- 

 tion, such as the cyanide-insensitive respiration of insects (Pappenheimer and 

 Williams, 1954) and the ascorbate-dependent, cyanide-insensitive DPNH 

 oxidase activity of a preparation from adrenal 'microsomes' (Kersten, Kersten 

 and Staudinger, 1958). 



Alternatively, reduced microsomal cytochrome is known to be oxidized 

 rapidly in vitro by a variety of reversibly reducible substances such as cyto- 

 chrome c, ferric salts and a number of dyes, and analogous electron acceptors 

 in vivo might serve as mediators of terminal respiration, with electrons being 

 transported further to oxygen either non-enzymically, if the mediator is 

 autoxidizable, or enzymically. Model oxidase systems may be constructed 

 by addition of mediator systems to microsomal cytochrome, but there is no 

 direct evidence for such a system in vivo. Thus, while addition of cytochrome 

 c and isolated mitochondrial preparations to microsomal cytochrome 

 permits rapid electron transport from the microsomal cytochrome to oxygen 

 in vitro (Strittmatter, unpublished work), it is not known whether significant 

 terminal electron transport from microsomal cytochrome via cytochrome c 

 and mitochondrial cytochrome oxidase could occur in the intact cells. In 



