A NOTE ON THE MECHANISM OF IODOACETATE POISONING OF MUSCLE

¹ The Department of Physiology, University of Edinburgh

1. Isolated muscles of Rana esculenta were immersed in Ringer's solution containing sodium iodoacetate (N/1000), and the effect of the drug was followed in two ways: (i) the suppression of glycolytic activity, and (ii) the liberation of iodide (presumed to result from an interaction between iodoacetic acid and glutathione of muscle).

2. At 0° C. the glycolytic activity of muscle is reduced to of normal in 2 hours, and is completely suppressed in 8 to 9 hours. But no iodide is liberated during the first two hours of immersion, and even at the end of 8 to 9 hours the amount produced is less than 10 per cent. of the maximum that the muscle is capable of liberating.

3. This maximum iodide liberation requires about 36 hours contact between iodoacetate and muscle at room temperature, and amounts to about 0·07 millimols per 100 grm. of muscle, irrespective of the amount and concentration of iodoacetate in the system, provided there. is an excess. This quantity is equivalent to 25 mg. of reduced glutathione per 100 grin. of muscle.

4. At 40° C. the inhibition of lactic acid production becomes apparent in about 10 minutes, and maximum poisoning effect is attained in 30 to 40 minutes. Liberation of iodide, on the other hand, begins in about 20 minutes, and the maximum production takes as much as 3 to 4 hours.

5. These results do not support the view that the suppression of glycolytic activity of muscle depends upon an interaction between iodoacetic acid and glutathione, although they do not rule out the possibility of the formation of an addition compound.

I am deeply indebted to Dr P. Eggleton for help and guidance generously given.

The expenses of this research were defrayed from a grant from the Moray Endowment Fund.