THE SIGNIFICANCE OF RESPIRATORY CHAIN 



OXIDATIONS IN RELATION TO METABOLIC 



PATHWAYS IN THE CELL 



By F. Dickens 



Courtauld Institute of Biochemistry, 

 Middlesex Hospital Medical School, London 



The term 'respiratory chain' has been interpreted with various meanings by 

 writers on tills subject. For the present purpose we can adopt the definition 

 of Slater (1958a), in his comprehensive review of the respiratory chain in 

 animal tissues to include all those intermediates which are actual carriers of 

 iiydrogen atoms (or electrons) in the path from substrate to oxygen. 



Unfortunately there is at present much uncertainty not only concerning 

 the sequence of these carriers, but even about which of them actually are on 

 the respiratory chain. It will be necessary first to mention some of these 

 difficulties. The respiratory chain itself may very likely offer alternative 

 pathways, such as that proposed by Martins (1959), for example, who 

 considers that in mitochondria there may be two routes linking pyridine 

 nucleotides with cytochrome r, only one of which (that presumed by Martius 

 to involve vitamin K) is accompanied by oxidative phosphorylation. In the 

 Martius scheme, either reduced di- or tri-phosphopyridine nucleotides 

 (DPNH or TPNH; Martius and Marki, 1957) can reduce vitamin K by 

 means of a specific flavoprotein called vitamin K reductase (fpg, Fig. 1), 

 which is blocked by very low concentrations of dicoumarol (ca. 10"^ m), and 

 oxidation of either TPNH or DPNH by this route should therefore produce 

 high energy phosphate. However, the weight of the present evidence is 

 against this stage of TPNH oxidation as a source of 'high energy' phosphate 

 (see later). The alternative route proposed by Martius for DPNH oxidation 

 is a non-phosphorylating one, via DPNH-cytochrome c reductase leading to 

 reduction of either cytochrome c or q (cf. Fig. 1). This reaction is thought 

 to prevail when phosphorylation is uncoupled from respiration. A number of 

 difficulties in the way of accepting this hypothesis, especially the lack of 

 effect of dicoumarol on the oxidation state of cytochrome b (Chance) and 

 the fact that dicoumarol blocks all three of the oxidative phosphorylation 

 sites in the respiratory chain (Lehninger) are pointed out in the discussion of 

 Martius's paper at the Ciba Symposium on Regulation of Cell Metabolism 

 (1959). 



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