128 III. OXIDATION AND METABOLISM 



had been given. Also, the feeding of butyrate to unfasted rats did not 

 lead to significant deviation from the control levels. 



It should be pointed out that sodium butyrate is widely employed as a 

 ketogenic agent to produce an exogenous ketonuria. If it were converted 

 to an appreciable extent to glucose, this would result in a marked reduction 

 in the level of ketonuria. Although Buchanan et al.^^^ did obtain some 

 radiocarbon in the glycogen fraction after feeding isotopic butyrate, the 

 glycogen deposited comprised less than 5% of the ingested butyrate, and 

 amounted to only about 3 mg. Obviously, the formation of glucose does 

 not represent a major pathway of transformation of butyrate. 



(d) Formation from Odd-Chain Fatty Acids. The question as to whether 

 or not odd-chain fatty acids are ketogenic is disputable. In tests in which 

 the sodium salts of valeric and heptanoic acids were ingested-^ as well as 

 in studies in which the ethyl esters of propionic, valeric, heptanoic, non- 

 anoic, or undecanoic acids'^ were fed to fasting rats, only a slight ketonuria 

 occurred if, in fact, any increase in ketone body excretion over the control 

 level could be noted. On the other hand, glycogen synthesis was observed 

 when the sodium salts of the C3, C5, C7, and Cg acids were administered,^^ 

 and also when the ethyl esters of C3, C5, C7, C9, and Cu acids were given. ^^ 

 In contradistinction to this finding, the sodium salts of the even-chain 

 acids or their ethyl esters gave rise to an intense ketonuria when fed to 

 fasting rats, and no glycogen formation could be observed. Krainick^^* 

 injected solutions of the various fatty acids into human subjects. Although 

 he was able to demonstrate typical curves showing increased blood levels 

 of ketone bodies in the case of C4, Ce, Cs, and Cu acids, no increases were 

 obtained with the odd-chain acids from C3 to Cu, except a minimal rise in 

 the case of C7. Embden and Marx,^ likewise, were unable to detect any 

 ketone bodies in the fluid used in the perfusion of surviving livers of dogs 

 after odd-numbered fatty acids had been added to it. 



On the other hand, MacKay and collaborators^^ reported that a keto- 

 nemia obtained when the ethyl or glycerol esters of valeric, heptanoic, and 

 undecanoic acid were fed to rats; no quantitative data were available, but 

 approximately the same levels of blood ketones were found as in the case of 

 even-numbered acids. Jowett and QuasteP^ also reported ketogenesis 

 when odd-numbered fatty acids were incubated with liver slices. However, 

 in every case, the even-numbered fatty acids produced more ketone bodies 

 than did the odd-chain acids in ratios varying between 2:1 and 5:1. 

 Califano^^^ reported that liver shces produced only small amounts of ketone 

 bodies when incubated with odd-chain fatty acids. 



"3 H. G. Krainick, Klin. Wochschr., 19, 803-808 (1940). 

 «3* I. Califano, Biochem. Z., 289, 354-364 (1937). 



