Intermediary carbohydrate metabolism: The effect of sodium iodoacetate on glyoxalase.

INTRODUCTION. THE keystone of a theory of intermediary carbohydrate metabolism, put forward by Dakin and Dudley [1913, 3; 1914] is the ketonic aldehyde, methylglyoxal. The postulation of this substance as the catabolic precursor and anabolic successor of lactic acid (CH3. CO.CO = CH3.CHOH.COOH) correlates in an intelligible scheme many of the known metabolic changes of carbohydrates. The discovery of the enzyme glyoxalase [Dakin and Dudley, 1913, 1], which, detectable in all mammalian tissues with the exception of the pancreas, rapidly converts methylglyoxal into lactic acid, provided substantial support for the theory, and a large body of evidence, subsequently collected, has upheld the opinion that methylglyoxal is, in fact, an intermediary compound in normal glycolysis [see e.g. Toenniessen and Fischer, 1926; Ariyama, 1928, 2]. Now Lundsgaard recently [1930, 1] independently rediscovered the fact, first noted by Pohl [1887], that the muscles of animals, poisoned with iodoacetic (or bromoacetic) acid, form no lactic acid under conditions in which normal muscle produces considerable amounts of this substance. Here then is a simple chemical substance which prevents the normal breakdown of carbohydrate, presumably by interfering with one or more of the catabolic reactions involved, and possibly, therefore, with that brought about by glyoxalase. The experimental examination of this possibility, which forms the basis of this paper, proves that sodium iodoacetate is in fact a powerful inhibitor of the action of glyoxalase.