F. Dickens
1933
Citations
0
Influential Citations
92
Citations
Quality indicators
Journal
The Biochemical journal
Abstract
SINCE Lundsgaard [1930] drew attention to the remarkably toxic nature of certain of the halogenacetic acids and their role as powerful and selective inhibitors of lactic acid formation and of alcoholic fermentation, these compounds have assumed great importance in physiology, and the numerous investigations of fundamental value to the theories of muscular contraction, tissue glycolysis and fermentation which have resulted show the usefulness of these labile halogen compounds as reagents in the study of intermediary tissue metabolism. But in spite of the many investigations, in no one case has the mechanism of their action been explicable in any clearly defined way, though various suggestions, such as those of Waldschmidt-Leitz and Schiffner [1932] and of Bersin [1932], have been advanced from time to time. In view of the importance of the iodoacetate reaction, it was decided to investigate what appeared to be one of the simplest physiological transformations known at the time to be inhibited by iodoacetic acid, namely the conversion of methylglyoxal into lactic acid: a type of oxido-reduction of great interest and perhaps one directly concerned in glycolysis. Indeed Dudley [1931], who discovered the inhibitory action of iodoacetic acid on this keto-aldehyde mutase system, considered that this might weli be the mode of action of the halogenacetic acids on the glycolytic process. It is true that Lohmann [1931], shortly after, found that in his glyoxalase preparations a much higher concentration of iodoacetate was needed to stop glyoxalase action than was required to check the formation of lactic acid by the Meyerhof muscle extract; he therefore considered that it was unlikely that the inhibition of muscle glycolysis could be due to poisoning of the glyoxalase system. Nevertheless this point could not be said to be definitely cleared up, and during an attempt to investigate it further the work to be described in the present paper, which sheds some light on the mechanism of iodoacetate poisoning of glyoxalase, arose. In view of the possibility that the method of preparation of the extracts might affect the concentration of iodoacetate necessary, the behaviour of