TRIGLYCERIDES AND FATTY ACIDS 167 



World War II, the further exposition of the theory occurred somewhat 

 later. This investigator^^'^^^'^^" suggested that the oxidation of /3-keto 

 acids was accelerated by an enzyme, which he called " citrogenase" ; this 

 caused a condensation of oxaloacetic acid and of higher jS-keto acids to 

 form citric acid or other tricarboxylic acids in equilibrium with it. A 

 corresponding enzj^me was present, not only in the heart muscle,^* but 

 likewise in the kidney, where it was shown to occur in the insoluble particles 

 from homogenized cortex.^^^-^^^ Martius^^' also confirmed the condensa- 

 tion of oxaloacetic and (3-keio acids. However, neither Weil-Malherbe^^^ 

 nor Krebs and Eggleston^^^ were able to confirm the occurrence of citro- 

 genase, the enzyme involved in citric acid synthesis. Thunberg^^^ reviewed 

 the formation, occurrence, and function of citric acid. 



Buchanan and co-workers^^^ reported that intermediates of the Krebs 

 cycle, when added to a homogenate of guinea pig kidney cortex, stimulated 

 the disappearance of acetoacetate. It was concluded that the mechanism 

 is similar to that suggested by Wood et al}^^ for the oxidation of pyruvate. 

 Ct's-aconitic acid was assumed to be the condensation product of oxaloacetic 

 acid and of a 2-carbon intermediate common to the metabolism of pyruvate 

 and of acetoacetate. It is now believed that the acetate involved in the 

 condensation with oxaloacetate is an active form which can readily be 

 synthesized from acetoacetate. 



There has been considerable confusion as to whether or not acetic acid 

 and acetoacetate follow the same course of metabolism, and whether they 

 are both metabolized in conjunction with the tricarboxylic cycle. Quastel 

 and Wheatley^^^ found that malonate, which inhibits the succinoxidase 

 system,^^"'^^^ slows down the oxidation of both fatty acids and ketone 

 bodies. In fact, they recognized that the oxidation of these substances 

 was related to the tricarboxylic acid cycle. Edson and Leloir^*^ confirmed 



"9 F. L. Breusch, Enzymologia, 11, 169-173 (1944). 



"0 F. L. Breusch and H. Keskin, Enzymologia, 11, 243-252 (1944). 



"1 H. Wieland and C. Rosenthal, Ann., 554, 241-260 (1943). 



"2 F. E. Hunter and L. F. Leloir, /. Biol. Chem., 159, 295-310 (1945). 



"3 C. Martius, Z. physiol. Chem., 279, 96-104 (1943). 



"4 H. Weil-Malherbe, Nature, 153, 435-436 (1944). 



53* H. A. Krebs and L. V. Eggleston, Nature, 154, 209-210 (1944). 



"« T. Thunberg, Physiol. Revs., S3, 1-12 (1953). 



"' J. M. Buchanan, W. Sakami, S. Gurin, and D. W. Wilson, /. Biol. Chem., 157, 

 747-748 (1945). 



^^ H. G. Wood, C. H. Werkman, A. Hemingway, and A. O. Nier, J. Biol. Chem., 139, 

 483-484 (1941). 



"s J. H. Quastel and A. H. M. Wheatley, Biochem. J., 29, 2773-2786 (1935). 



*« R. P. Gever, L. W. Matthews, and F. J. Stare, J. Biol. Chem., 182, 101-108 (1950). 



"1 N. L. Edson and L. F. Leloir, Biochem. J., 30, 2319-2332 (1936). 



