194 III. OXIDATION AND METABOLISM 



experimental data of Mirsky^^^ and of Mirsky and Broh-Kahii."^ These 

 workers reported that ketosis coiikl not l)e produced in eviscerated rabbits. 

 Crandall et al.,~^^ in experiments with imanesthetized angiostomized dogs 

 (London cannulas in the portal and hepatic veins), found that ketone 

 bodies were produced in the liver in fasted animals but not in unfasted 

 ones. The synthesis of ketone bodies in the liver has been demonstrated by 

 liver perfusion and by incubation of liver slices in ^;^Yro.*^•^''*■^^*■^^^■^^^'^^^ 

 Stadie, Zapp, and Lukens''^* likewise observed that the R. Q. of isolated 

 liver which is oxidizuig chiefly fat is as low as 0.30. If one excludes the 

 conversion of fat to carbohydrate as an explanation for this value, it can 

 best be explained as due to an incomplete oxidation of fatty acids associ- 

 ated with the production of ketone bodies. 



(d) Fat Turnover in the Liver. Fatty acids have a short half-life, 

 probably about one day, in the liver, as contrasted with a period of five to 

 nine days in the body carcass, and ten to fifteen days in brain tissue."' 

 Hevesy and co-workers"^ noted that, in spite of the usual half-life of fatty 

 acids of only one day in the livers of mice, an actual decrease of concentra- 

 tion of 50% has been demonstrated within thirty to sixty minutes after the 

 injection of CMabeled acetic acid. This suggests that a rapidly renew- 

 able fatty acid fraction may be present in the liver. Beeckmans and 

 Elliott''" believe that this effect may be ascribed to the rapid turnover of a 

 minor portion of the fatty acid present. However, there is no evidence of 

 such a rapidly metabolizing fraction in the brain or muscle fatty acids."® 



b. Extrahepatic Oxidation of Fat. Considerable circumstantial evidence 

 indicates that fat must be burned directly by the extrahepatic tissues. 

 Thus, the total quantity of ketone bodies formed by the liver of the diabetic 

 animal is not large enough to account for the calories obtained from fat."^'"^ 

 Moreover, it is not possible to remove the ketone liodies from the blood 

 rapidly enough, nor to accelerate their oxidation sufficiently, to provide 

 the entire caloric needs of the animal."'^*' '^^^ 



In addition, there is positive evidence of the use of fat by non-hepatic 

 tissues. Thus, measurements of respiratory quotients in resting, depan- 



•"6 W. C. Stadie, J. A. Zapp, Jr., and F. D. W. Lukens, /. Biol. Chem., 132, 423-443 

 (1940). 



«™ G. Hevesy, R. Ruyssen, and M. L. Beeckmans, Experientia, 7, 144-146 (1951). 

 677 L. M. Beeckmans and G. de Elliott, Nature, 167, 200-201 (1951). 

 «78 W. C. Stadie, J. Clin. Invest., 19, 843-861 (1940). 



679 W. C. Stadie, Ann. Internal Med., 15, 783-797 (1941). 



680 N. Nelson, I. Grayman, and I. A. Mirsky, /. Biol. Chem., UO, 361-364 (1941). 



681 E. T. Waters, J. P. Fletciher, and I. A. Mirsky, Am. J. Physiol, 122, 542-546 (1938). 



