POLYCARBOXYLIC ACIDS 313 



nephrotoxic action.*''''-'^'- Flaschciitriiser and BernharcP^ reported that 

 sel)aeic acid (Cio) was utiHzed only to the extent of 40%, and that the rest 

 of the injected acid appeared in the urine; however, when one acid group 

 was blo(!ked, the acid was largely utilized, and only 10% was excreted in 

 the urine. 



Azelaic acid (C9) was investigated by Smith. ^•^ This acid is of con- 

 siderable importance, since it is formed when the unsaturated acids having 

 a double bond in the C9-C10 position (which includes most physiologic un- 

 saturated fatty acids) are oxidized by potassium permanganate. If a 

 rupture at the unsaturated linkage occurs in the case of oleic acid, one 

 would expect azelaic acid to be one of the intermediates in its biologic 

 oxidation. Smith^'* reported that azelaic acid was oxidized by dogs in 

 amounts smaller than would be produced if oxidation took place at the 

 double bond. It was utilized at an average rate of only 58% (with a 

 range of 29 to 92%) when the doses varied from 10.5 to 44.9 g. It was 

 therefore indicated that oxidation of the 9,10-unsaturated acids does not 

 normally involve a rupture at the double bond. The fact that no 

 gh^cogen is formed from the nonanoic (pelargonic) acid, which would be 

 produced simultaneously with azelaic acid, has likewise been interpreted as 

 precluding the 9,10-rupture of oleic acid as a normal in vivo pathway of 

 oxidation. ^^ 



The mechanism of oxidation of the dicarboxyhc acids which do dis- 

 appear is not clear. Most of the evidence for co-oxidation has indicated 

 that /5-oxidation proceeds from the carboxyl group, with the formation of 

 dicarboxyhc acids having two less carbon atoms than the parent acid. 

 This was proved by Bernhard,^^ w^ho demonstrated a dilution of the 

 deuteriosuberic acid eliminated in the urine after the feeding of deuteriosu- 

 beric acid, when C12 or Cie dicarboxyhc acids were also fed. However, 

 since the odd-numbered diacids, pimelic (C7) and azelaic (C9), are ap- 

 parently no more toxic than are the even-chain acids, adipic (Ce) and 

 suberic (Cg), Bloor^^ suggests that it is improbable that a direct /3-oxidation 

 of these acids occurs. Baer and Blum^- reported that adipic (Ce), pimelic 

 (C7), and suberic (Cs) acids behaved like glutaric (Cs) acid in inhibiting 



^2 J. Baer and L. Blum, Naunyn-Schmiedeberg's Arch, exptl. Pathol. PhannakoL, 65, 

 1-33(1911). 



" B. Flaschentrager and K. Bernhard, Z. phijsiol. Chem., S40, 19-22 (1936). 



3" H. G. Smith, ./. Biol. Chem., 103, 531-535 (1933). 



'5 J. S. Butts, H. Blunden, W. Goodwin, and H. J. Deuel, Jr., /. Biol. Chem., 117, 

 131-133(1937). 



9« K. Bernhard, Helv. Chim. Acta, U, 1412-1425 (1941). 



" W. R. Bloor, Biochemistry of the Fatty Acids, Reinhold, 1943, p. 321. 



