226 GEORGE H. HOGEBOOM AND WALTER C. SCHNEIDER 



localized in other cell fractions and that the Krebs cycle is an integrated 

 function of several cell structures. Additional evidence for the latter view 

 has been provided by the finding that the oxidation of a-ketoglutarate and 

 oxalacetate is stimulated by the addition of other fractions which by them- 

 selves are inactive.'"'' •'°- 



A reaction that also has an important bearing on the role played by the 

 mitochondrion in the integrated activities of the cell is the synthesis of 

 adenosine triphosphate through oxidative phosphorylation (Table II). 

 In the presence of an oxidizable substrate, such as a-ketoglutarate, glut- 

 mate, or succinate, and with added inorganic phosphate, Mg^"+, and cyto- 

 chrome c, adenosine diphosphate is rapidly converted to ATP by isolated 

 mitochondria. The presence of adenylate kinase, which establishes an 

 equilibrium among ADP, ATP, and adenosine-5-phosphate, makes it 

 possible for mitochondria also to convert the latter compound to ATP. 

 The complexity of the oxidative phosphorylation reaction and the fact 

 that it is subject to interference by side reactions makes difficult a defini- 

 tive study of its intracellular distribution. The data of Siekevitz'"^ indicate, 

 however, that it may be an exclusive function of mitochondria. A mag- 

 nesium-activated adenosine triphosphatase, that removes only the terminal 

 phosphate from ATP,'^* is also concentrated in this fraction but, as shown 

 by Kielley and Kielley,'"'' is inactive when the mitochondria are freshly 

 isolated in isotonic sucrose solution. The latter investigators have also 

 demonstrated that when the mitochondria are disrupted in a Waring 

 Blendor, the adenosinetriphosphatase is rendered highly active and re- 

 mains attached to fragments sedimentable only at high centrifugal forces, 

 whereas adenylate kinase passes into solution, and the oxidative phos- 

 phorylation reaction disappears.'^* The finding that the adenosinetriphos- 

 phatase activity is strongly inhibited by adenosine diphosphate and that 

 mitochondria contain considerable quantities of the latter compound'^® 

 may account, at least in part, for the fact that the intact particles show 

 no adenosinetriphosphatase activity. The means by which the mitochon- 

 drion is able to control these three reactions is an interesting problem and 

 may depend on the spatial relationship of the enzyme systems within the 

 particle. 



Because of its high energy phosphate bonds, ATP occupies a central 

 position in cellular metabolism, taking part in many reactions that are 

 widely distributed among the various cell structures. ATP has, of course, 

 received considerable attention as a possible source of energy for synthetic 

 reactions. Our present knowledge of the mechanism of biosynthesis of 

 this compound has provided a strong foundation for Claude's suggestion" 

 that the mitochondrion is the power plant of the cell. 



As shown in Table III, other enzymes apparently associated with mito- 



136 W. W. Kielley and R. K. Kielley, /. Biol. Chem. 200, 213 (1953). 



