The History of the Tricarboxylic Acid Cycle

and vision? It was of course nothing ofthe kind, but a very slow evolu- tionary process, extending over some five years beginning (as far as I am involved) in 1932. At that time the problem of the intermediary stages ofthe pathways ofanaerobic energy metabolism—glycolysis and alcohol fermentation—had been established in outline by 1932, but knowledge of the pathways ofoxidation was very fragmentary. What was known can easily be summarized. There was the principle (though not the enzymic mechanism) of the ^-oxidation of fatty acids. There was the concept of oxidative deamination of amino acids and of the decarboxylation of the resulting a-ketonic acids. A surveyoftheknowledgeofintermediary path- ways ofoxidation in the early 1930s is to be found in Oppenheimer (1). The only hypothesis outlining a pathway of the intermediary stages of carbohydrate oxidation was that put forward by Thunberg (2) and sup- ported by Knoop (3) and Wieland (4). It assumed that two molecules of acetate—formed from lactate via pyruvate or by /3-oxidation of fatty acids—condensed to form succinate which was taken to undergo oxida- tion via fumarate, malate, oxaloacetate and pyruvate to form one mole- cule ofacetate: coo- coo-coo-coo-