Effects of organic arsenicals on enzyme systems.

Investigations have been carried out by us in the Biochemical Laboratory of the Cardiff City Mental Hospital during 1938, 1939 and early 1940 on the effects of organic trivalent and pentavalent arsenic compounds on proteins and enzymes. The work was primarily undertaken to elucidate the biochemical basis of the trypanocidal and anti-spirochaetal action of a variety of organic arsenic compounds used in the treatment of syphilis. Investigations by Hawking, Hennelly & Quastel (1937) had already shown that administration of the pentavalent arsenical tryparsamide into the body led to the appearance of trivalent arsenic compounds, of high trypanocidal activity, in the spinal fluid. On the other hand, administration of organic trivalent arsenic compounds did not lead to the excretion of active trivalent arsenic compounds in the spinal fluid. Work was therefore undertaken to discover the manner of combination of organic trivalent and pentavalent arsenic compounds with tissue proteins and enzyme systems. It was inevitable that our work led us into problems connected with the mechanism of action of certain war gases (e.g. lewisite) and with the question of reversibility of enzyme systems inactivated by arsenic compounds. Whilst we, ourselves, did not work with actual war gases, our results bore on the problems involved and for this reason publication of our results was not allowed during the war. A report, however, was submitted to the Medical Research Council in November 1940, and an extract containing the main conclusions was published in Nature (Gordon & Quastel, 1947) by permission of the Secretary of the Medical Research Council. The. present paper contains the results of investigations made by us on the effects of organic arsenic compounds on enzyme systems during 1938, 1939 and early 1940; they are the results on which the conclusions, already published by Gordon & Quastel (1947), are based.