Studies on Micrusoinal Cytocliroincs All 



particular, the availability of soluble cytochrome c and the accessibility of 

 extramitochondrial electron donors such as soluble cytochrome c to the 

 terminal respiratory chain of intact mitochondria in vivo are questionable 

 (cf. Chance and Williams, 1955; Wainio and Cooperstein, 1956; Slater, 

 1958). If a microsomal cytochrome-like substance were localized within the 

 mitochondrial structure, it might more readily be involved significantly in 

 terminal respiration. 



While, therefore, microsomal cytochrome might play a role in terminal 

 respiration of cells with low rates of oxygen consumption and may contribute 

 to the usually minor cyanide-insensitive respiration, there is as yet no com- 

 pelling evidence that this substance is responsible for a significant portion 

 of terminal respiration in actively respiring cells. 



''Reductive'' Synthetic Reactions 



Another possibility which merits consideration is that microsomal cyto- 

 chrome primarily funnels electrons available from DPNH (or TPNH) to 

 acceptors in synthetic processes that are reductive in character, such as the 

 reductive synthesis of fatty acids or steroids, or which involve elements of 

 both reduction and oxidation, such as hydroxylation reactions (requiring 

 both DPNH (or TPNH) and molecular oxygen). The rather low oxidation- 

 reduction potential of microsomal cytochrome would make it a suitable 

 mediator for transfer of electrons in such processes requiring reductive 

 capacity. The localization of the cytochrome in microsomes would be in 

 keeping with such a role, as the microsomes, or the endoplasmic reticulum 

 from which they are derived, are recognized as the site of or are required for 

 a variety of synthetic processes, including protein biosynthesis (Littlefield, 

 Keller, Gross and Zamecnik, 1955), cholesterol synthesis in liver (Bucher and 

 McGarrahan, 1953), and a variety of hydroxylation reactions required for 

 formation and metabolism of steroids, various aromatic compounds, etc., 

 in the liver or adrenal (Ryan and Engel, 1957; Mason, 1957; Kersten, 

 Leonhauser and Staudinger, 1958). It may therefore be significant that 

 microsomal cytochrome is present in large concentration in the rather 

 abundant endoplasmic reticulum of liver, an organ with a relatively reductive 

 internal environment and a high capacity for many synthetic reactions, and 

 that other tissues in which microsomal cytochrome or apparently similar 

 pigments are reportedly present are also sites of specialized synthetic pro- 

 cesses or of transport phenomena which may involve elements of synthesis. 



The possible participation of microsomal cytochrome in hydroxylation of 

 steroids by adrenal microsome preparations has recently received considerable 

 attention (see above). A model system of chelated iron salts, ascorbic acid 

 and oxygen can produce hydroxylation reactions (Udenfriend, Clark, Axelrod 

 and Brodie, 1954), and it has been suggested that the haemin of microsomal 

 cytochrome might similarly provide the site at which electrons from DPNH 



