VOL. 12 (1953) BIOCHIMICA ET BIOPHYSICA ACTA 239 



THE PATHWAYS OF ACETATE OXIDATION^ 



by 



E. S. GUZMAN BARRON and F. GHIRETTI** 



Chemical Division, Department of Medicine, 

 The University of Chicago, III. {U.S.A.). 



The modern concepts of cellular respiration and of biological oxidations to a large 

 extent were born from the discoveries of Warburg. Warburg isolated and crystallized 

 the activating proteins ; he discovered two of the three oxidation-reduction systems that 

 mediate in the transfer of electrons from substrate to molecular oxygen, the pyridine 

 nucleotides and the flavoproteins ; and he also discovered the last link to oxygen among 

 the iron-porphyrin enzymes, cytochrome oxidase or Sauerstoffiibertragendes Ferment. 

 Warburg and Michaelis formulated the fundamental principles. They trail-blazed the 

 road. It is for the generations who succeed them in this search to clear the road and to 

 penetrate into the mechanism of biological oxidation-reductions. Once the mechanism 

 of the first phase of carbohydrate metabolism — the anaerobic reactions from glucose 

 to pyruvic acid — were understood (thanks to Warburg and Meyerhof), there remained 

 the oxidative phase, starting from the oxidation of pyruvic acid to acetate or acetyl- 

 coenzyme A. The pathways of acetate oxidation have been diligently searched during 

 the last fifteen years, without, however, general agreement about their relative impor- 

 tance in cellular respiration, or even in some cases about their existence. In animal 

 tissues, both vertebrate and invertebrate, all the published experiments support the 

 contention that oxidation of acetate proceeds via the tricarboxylic acid cycle^'^, i.e., 

 by the condensation of acetylcoenzyme A with oxalacetate. In plants, oxidation pro- 

 ceeds also through this pathway^'^. In some moulds and bacteria, specially in those 

 micro-organisms growing in acetate as the main carbon source, there have been proposed 

 two alternative pathways, the dicarboxylic acid cycle^"^ or oxidation to glycolic acid^". 

 Other alternative pathways have also been suggested^^"^^. Solution of this problem 

 is complicated by the semipermeable properties of the cell membrane, which in many 

 cases is impermeable to di- and tri-carboxylic acids even when these are present largely 

 as undissociated acids. It was decided to reinvestigate the possible existence of alterna- 

 tive pathways in those cells which had been presented as oxidizing acetate either by the 

 dicarboxylic acid cycle or through glycolic acid. In all these cells were found the enzymes 

 for the synthesis of citric acid and for the oxidation of zsocitric acid, a demonstration 

 that acetate can be oxidized via the tricarboxylic acid cycle. There was also, however, 

 in these cells, as well as in other cells and tissues examined, anaerobic oxidation of ace- 

 tate in the presence of coenzyme A, diphosphopyridine nucleotide (DPN), and flavin 



This work was supported by grants from the Biological Sciences Division of the Office of Naval 

 Research and by the Douglas Smith Foundation for Medical Research of the University of Chicago. 

 Fellow of the Public Health Service, National Cancer Institute. 



References p. 24g. 



