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In 1938, Hopkins and coworkers (1, 2) showed that succinic dehydrogenase could be inactivated by oxidized glutathione (GSSG) and could be reactivated by reduced glutathione (GSH). They interpreted these results to mean that the active enzyme requires i n t a c t --S H groups and that when these are converted to the --S --S --form of the enzyme, the dehydrogenase is inactivated. Any assumption that the functioning of the enzyme involved an oscillation between the SH and the --S---S---form of the enzyme seemed to be definitely eliminated, however, by the fact that the --S --S --form could not be reduced by succinate. Thus the function of the SH group in succinic dehydrogenase has remained an unsolved problem.Although many proteins contain SH groups, very little is known about the structural relationship of the SH group to the rest of the molecule. Even in the case of egg albumin, in which the SH groups have received the most careful study, the mechanism by which the SH groups of native egg albumin are shielded from some sulfhydryl reagents and not from others remains obscure (3). In the case of succinic dehydrogenase, the presumptive SH group (1, 2) is associated with function, and the reaction of the protein with sulfhydryl reagents should be demonstrable on the basis of determinations of the amount of active enzyme remaining. Furthermore, since it is an oxidative enzyme, the measurement of oxygen uptake makes possible a continuous appraisal of the amount of active enzyme at any given moment. We have previously established the test conditions for the measurement of the activity of this enzyme (4, 5). The rate of oxygen uptake is a valid measure of succinic dehydrogenase activity in this system since cytochrome c and cytochrome oxidase, which are needed to complete the reaction with oxygen, are present in excess. The activity of the enzyme is so great under the proper conditions that the extraneous matter present in the enzyme preparation does not interfere with the study of the reaction.At present, inhibitor studies appear to constitute the only available means of establishing the presence of SH groups in succinic dehydrogenase and of determining their r61e in the function of the enzyme.

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483gest that this approach would produce data more reliable than red cell uptake of radioiron, especially during weak or short-lived effects. Hodgson et aZ. (12) have reached the same conclusion following use of this method to study bone marrow stimulation. These experiments are being extended to determine the limits of accuracy and sensitivity of this method.We studied the depression of plasma radioiron turnover rates in rats following X-irradiation. The depression is prompt (maximal by 24-30 hours) and, at 24 hours post-irradiation, is directly related to dose between 50 r and 300 r. Recovery occurs by the 6th post irradiation day, indicating that subsequent anemia is more likely due to hemorrhagic diathesis than bone marrow dysfunction. Sensitivity of the radioiron turnover method permitted a study of bone marrow response at frequent short intervals after irradiation. Summary.We gratefully acknowledge technical assistance of Mr. Alfred E. Seaton.1. Jacobson, Leon 0.

a profound fall in urinary excretion of uric acid. Curate declined from a mean control level of 10.4 ml/min. to a mean minimum of 1.4 ml/min. The uricosuria produced by salicyla te and probenecid was temporarily abolished by lactate. The significance of these findings is discussed. 1. Gi,bson, H. V., and Doisy, E. A., J. Biol. Chem., 2. Quick, A.Frawley et al. ( I ) recently demonstrated that simultaneous administration of ethylpnitrophenyl thionobenzenephosphonate (EPN) and S-( 1,2-dicarbethoxyethyl) -0, 0dimethyl phosphorodithioate (malathion) to rats and dogs causes marked potentiation of the acute and subacute toxicity of these insecticides. The widespread use of organic phosphorus-containing insecticides on food crops makes it possible for .the diet of man and domestic animals to contain low quantities of several of these compounds. For an accurate evaluation of the health hazards which might result from potentiation of the action of cholinergic organic phosphates it was desirable to have a sensitive, direct method for measuring the biochemical event responsible for the effect which couId be applied to the tissues of * This investigation was supported ,by grant from the U. S. Public Health Service. animals fed low levels of these insecticides. It has been observed by Cook et al.(2) that EPN inhibits the hydrolytic detoxification of malathion by rat liver homogenates in vitro.This observation provides a possible explanation for potentiation of the toxicity of malathion by EPN since the low mammalian toxicity of malathion is apparently highly dependent upon rapid and complete detoxification. The present communication describes a quantitative method for measuring inhibitory action of EPN on detoxification of malathion. Data are presented which show the applicability of this method for in vitro experiments and for measurements 03tissues taken from animals given acutely toxic and low dietary levels of EPN. The tissue distribution of the esterase which catalyzes the hydrolytic detoxification of malathion was also studied. Methods and materials. Adult male andat GEORGETOWN UNIV MED CTR on July 21, 2015 ebm.sagepub.com Downloaded from

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