The action of sulphydryl inhibitors upon isocitric dehydrogenase with especial reference to the behaviour of some trivalent arsenicals

Abstract

The effect of -SH inhibitors upon isocitric dehydrogenase from pig heart was studied. Some expts. were made with an enzyme prepared from ox kidney. The isocitric dehydrogenase prepns. needed Mn ions for activity and the inhibitory effect of phosphate was explicable as due to precipitations of Mn. Cu and Hg compounds were inhibitory and the inhibition was reversed by monothiols. With the heart enzyme, the monosubstituted arsenical compounds, arsenite and lewisite oxide, were non-toxic in the concns. tried; but the disubstituted compounds diphenylchloroarsine and some phenarsazines were toxic. Their toxicity to the enzyme was reversed by -SH glutathione and by British anti-lewisite (BAL). Maleate, chloroacetophenone, N mustard, alloxan, iodoacetate and iodoacetamide produced no inhibition, nor did p-aminobenzoate and Na fluoroacetate; some effect was found with iodosobenzoate. With the kidney enzyme lewisite oxide showed some toxicity not reversible by BAL. Some implications of these facts were discussed; it was concluded that isocitric dehydrogenase possessed a -SH grouping of unusual properties.