146 III. OXIDATION AND METABOLISM 



rats exhibit a higher level of ketonuria than do the males. This response 

 is identical with that of human subjects during fasting, and with that of 

 rats subjected to an exogenous ketonuria. Moreover, ketolytic substances 

 such as glucose tend to suppress the endogenous ketonuria, as would be 

 expected if it is assumed to be a physiologic condition. 



One might expect the endogenous type of ketonuria to be preferable to 

 the exogenous type for experimental studies, since the rate of production of 

 ketone bodies is constant in the first case, while it must be highest during a 

 few hours after the ketogenic acid is fed in the latter type of ketonuria. 

 However, substances which themselves are not ketolytic but become active 

 only after transformation to glucose or to some similar precursor may have 

 a less pronounced ketolytic effect when tested against an endogenous keto- 

 nuria than when the test animals have an exogenous ketonuria. In all 

 probabihty, this may be explained by the fact that the fatty Hver is unable 

 to bring about the essential changes in the metabolite which can be readily 

 effected by a liver containing a normal proportion of fat. For a further dis- 

 cussion of this point, the reader is referred to The Lipids, Volume II, 

 Chapter VI. 



Janes and Brady ^^^ noted that, when excessive doses of niacin were given 

 to rats fasted for periods up to five days, a marked ketonuria occurred. 

 It is stated that the ketogenic properties of niacin are not associated with 

 its acid or vasodilatory properties. It is possible that a choline deficiency 

 of sufficient magnitude may develop to bring about the ketonuria, as is 

 the case in the fatty livers. Niacin is detoxicated by methylation, and, 

 according to some reports, its administration in excessive amounts may 

 result in the development of fatty livers (see The Lipids, Volume II, 

 Chapter VI). 



d. Factors Altering the Extent of Ketonuria. The susceptibility of an 

 animal to ketosis is a function of species, age, sex, nutritional condition, 

 hormonal control, and many related factors. 



(a) Species as a Factor in Ketonuria. Man^^^'*^^ and monkey^^^'^^^ have 

 been generally considered to be the species most susceptible to a fasting 

 ketonuria. The level of ketonuria in the adult dog, which is classed as a 

 carnivore, is extremely low.**^-^^'* It has been stated that only a minimum 

 ketonuria develops during fasting in steers, goats, ^^^ rabbits, ^^^ and rats.**^"^*'' 



3" R. G. Janes and J. Brady, A?n. J. Physiol, 159, 547-550 (1949). 

 332 1. A. Mirsky, N. Nelson, I. Grayman, and S. Elgart, Endocrinology, 31, 264-270 

 (1942). 



3"T. E. Friedemann, /. Biol. Chem., 105, 335-341 (1934). 

 39* F. M. Allen, J. Metabolic Research, 4, 199-222 (1923). 

 395 L. Kallos-Defifner, Z. ges. exptl. Med., 92, 389-393 (1933). 



