33Q BIOCHIMICA ET BIOPHYSICA ACTA VOL. 4 (1950) 



IS ACETALDEHYDE AN INTERMEDIARY PRODUCT IN 

 NORMAL METABOLISM? 



by 



ERIK JACOBSEN 



Biological Laboratories of Medicinalco, Copenhagen S. {Denmark) 



Mainly through the work of Meyerhof, Parnas, Embden, and Cori, their collabo- 

 rators and pupils, the intermediary products of the first part of carbohydrate metabolism 

 are well known. The intermediary products have been isolated and the enzymes 

 involved thoroughly studied. It is now generally accepted that glycogen or glucose is 

 broken down to pyruvate through a series of phosphorylated compounds. Pyruvate 

 forms a "natural dividing point" between the anaerobic and the aerobic phases of 

 carbohydrate metabolism. It has, however, been extremely dilhcult to study the inter- 

 mediary products and the corresponding enzymes in volved in the further oxidation of 

 this substance. Several hypotheses concerning this part of carbohydrate metabolism 

 have been proposed. The experimental facts hitherto obtained seem to be best explained 

 by Krebs' citric acid cycle-theory. The individual processes are well known and need 

 no further description (Krebs, 1943). Nevertheless it is not known whether other 

 processes are also involved in the oxidation of pyruvate and alternative schemes have 

 been proposed. The early theory of Thunberg (1920) and Knoop (1923) suggests that 

 pyruvic acid is decarboxylated to acetaldehyde which is then oxidized to acetic acid. 

 This compound is in turn condensed to succinic acid. Their theory has now been aban- 

 doned, mainly because it has been impossible to demonstrate any formation of succinic 

 acid from acetic acid in living cells or cell extracts. It has, however, been shown by 

 several authors that acetaldehyde can be formed during tissue metabolism. In in vitro 

 experiments with minced tissues acetaldehyde has been trapped by means of aldehyde 

 fixatures following the technique of Neuberg. Hirsch (1923) identified acetaldehyde 

 formed in muscles of frogs or fishes. Neuberg and Gottschalk (1924) showed the 

 formation of acetaldehyde in different tissues of warm-blooded animals and their results 

 have been confirmed and enlarged by Palladin and Utevvski (1929), Gorr (1932), 

 Tanko, Munk, and Abonyi (1940) and others. Addition of pyruvate to the minced 

 muscles increases the yield of acetaldehyde (Utewski, 1929) and the formation of 

 acetoin, a condensation product of acetaldehyde and pyruvic acid, from pyruvate has 

 been shown by Green et al. (1941) and by Stotz, Westerfeld, and Berg (1944). In 

 animal tissues acetate was identified as an oxidation product of pyruvic acid by Krebs 

 and Johnson (1937), Weil-Malherbe (1937) and Long (1938). It was shown that 

 pyruvate anaerobically dismutes into lactate + acetate + carbon dioxide. Although 

 Krebs and Johnson emphasize that this process in animal tissues differs from that of 

 decarboxylation of pyruvic acid in microorganisms, it cannot be excluded with 

 certainty that acetaldehyde even in this process acts as an intermediary product. 

 References p. 334. 



