VOL. 4 (1950) ACETALDEHYDE IN NORMAL METABOLISM 33I 



Acetaldehyde is oxidized very rapidly in vivo (Lubin and Westerfeld, 1945) : and the 

 acetoin formed in vivo also appears to be very rapidly metabolized. 



Even if the citric acid cycle is the main path of the normal metabolism of pyruvic 

 acid and some of the results showing a possible formation of acetaldehyde from pyruvic 

 acid are due to artefacts in the sense that the biochemical processes only occur under 

 more or less abnormal conditions, it is still possible that pyruvate in normal metabolism 

 is partly broken down with acetaldehyde serving as an intermediary product. Hitherto 

 no means have been available to decide to what extent this secondary path plays a role 

 in the normal metabolic processes of the organism. 



At the present experiments performed in this laboratory are able to throw a light 

 on the question. 



Hald, Jacobsen, and Larsen (1948) have shown that individuals given tetra- 

 ethylthiuramdisulphide (Antabuse) will give a series of symptoms after ingestion of 

 minute amounts of alcohol. The occurrence of these symptoms is due to an increased 

 formation of acetaldehyde from alcohol, resulting in an increased concentration of 

 acetaldehyde in the blood (Hald and Jacobsen, 1948; Asmussen, Hald, and Larsen, 

 1948; and Larsen, 1948). If the metabolic rate of acetaldehyde is slowed after ingestion 

 of Antabuse, the increased concentration of this substance in the organism is easily 

 explained. Preliminary experiments in this laboratory showed, however, that no differ- 

 ence in the rate of acetaldehyde elimination in normal and Antabuse-treated animals 

 could be seen when acetaldehyde was given during short periods and in such an amount 

 that the final concentration of acetaldehyde in the blood was 20-25 mg/%. In collabo- 

 ration with Dr.'s Jens Hald and Valdemar Larsen I have made a series of further 

 experiments showing that the metabolic rate of small concentrations of acetaldehyde 

 is decreased in animals treated with Antabuse. These experiments will be published in 

 detail by Hald, Jacobsen, and Larsen. 



A series of rabbits weighing from 2.0-2.5 kg were given 0.50 g Antabuse 48, 24 

 and 16 hours prior to the experiment. The animals were anesthetized with urethan. 

 Blood samples were taken from a cannula inserted in the carotid artery. Coagulation 

 was prevented by the injection of 1500 units of heparin intravenously. Acetaldehyde 

 determinations were made by Stotz's method. A cannula was inserted into the jugular 

 vein. Two to ten per cent solutions of acetaldehyde in Tyrode's solution were infused 

 through the cannula at a known constant rate. The infusing apparatus consisted of 

 a 10-30 ml syringe, the piston of which was controlled by a screw driven mechanically 

 by a gramophone motor. The experiments generally lasted i ^-2 l^ hours. During this 

 period the infusion rate was maintained at a constant level which did not exceed the 

 capacity of the rabbits to metabolize acetaldehyde. There was no accumulation of 

 acetaldehyde in the tissues during the experiment. 



An average sized rabbit is usually capable of eliminating 7-8 mg acetaldehyde per 

 minute. The concentration of acetaldehyde in the blood was determined 30 minutes after 

 the beginning of the infusion and at intervals of '^U-^U hours. The levels of acetaldehyde 

 in blood corresponding to a fixed infusion rate of acetaldehyde varying between 0.75 mg 

 and 9 mg per minute were determined in two series of rabbits : one normal series, and 

 one consisting of rabbits treated with Antabuse in the manner described above. A con- 

 siderable variation of the blood acetaldehyde is noted from time to time although the 

 infusion rate was kept as constant as possible. The results of the experiments are 

 tabulated in Fig. i. A clear difference between the concentration of acetaldehyde in 

 References p. 334. 



