Abstract
The effect of disulfiram on succinate oxidase and succinate dehydrogenase activities of beef heart submitochondrial particles was studied. Results show that disulfiram inhibits both functions. Succinate and malonate suppress the inhibitory action of disulfiram when succinate dehydrogenase is stabilized in an active conformation. Disulfiram is not able to inhibit the enzyme when succinate dehydrogenase is inactivated by oxaloacetate. The inhibitory effect of disulfiram is reverted by the addition of dithiothreitol. From these results, it is proposed that disulfiram inhibits the utilization of succinate by a direct modification of an -SH group located in the catalytically active site of succinate dehydrogenase.
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References
Ackrell, A. C. B., Kearney, B. E., and Singer, T. P. (1978).Methods Enzymol. 53, 466–483.
Chávez, E., Bravo, C., and Jay, D. (1986).J. Bioenerg. Biomembr. 18, 93–99.
Chávez, E., Zazueta, C., and Bravo, C. (1989).J. Bioenerg. Biomembr. 21, 335–345.
Coles, C. J., and Singer, T. P. (1977).FEBS Lett. 82, 267–268.
Eneanya, D. I., Bianchine, J. R., Duran, D. O., and Andersen, B. D. (1981).Annu. Rev. Pharmacol. Toxicol. 21, 575–596.
Feinman, L., and Lieber, C. S. (1974). Liver disease in alcoholism. InThe Biology of Alcoholism. Vol. 3,Clinical Pathology. (Kissin, B., and Begleiter, H., eds.), Plenum Press, New York, pp. 303–338.
Goldstein, M., Mussacchio, J., Kopin, I., and Axelrod, J. (1964).Life Sci. 3, 763–767.
Graham, W. D. (1951).J. Pharm. Pharmacol. 3, 160–164.
Gutman, M. (1977).Biochemistry 16, 3067–3072.
Gutman, M. (1978).Mol. Cell. Biochem. 20, 41–60.
Gutman, M., Kearney, E. B., and Singer, T. P. (1971).Biochemistry 10, 2726–2733.
Hassinen, I. (1966).Biochem. Pharmacol. 15, 1147–1153.
Jurkovitz, M., Scott, K. M., Altschuld, R., Merola, A. J., and Brierley, G. P. (1974).Arch. Biochem. Biophys. 165, 98–113.
Kearney, E. B. (1957).J. Biol. Chem. 229, 363–375.
Kearney, E. B., Ackrell, B. A. C., Mayer, M., and Singer, T. P. (1974).J. Biol. Chem. 249, 2016–2020.
Kelner, M. J., and Alexander, N. M. (1986).J. Biol. Chem. 261, 1636–1641.
Kenney, W. C. (1975).J. Biol. Chem. 250, 3089–3094.
Kotlyar, A. B., and Vinogradov, A. D. (1984).Biochim. Biophys. Acta 784, 24–34.
Lee, C. P., and Ernster, L. (1966). InSymposium on the Regulation of Metabolic Processes in Mitochondria (Tage, J. M., Papa, S., Quagliariello, E., and Slater, E. C., eds.), Vol. 7, Elsevier North-Holland, New York, pp. 218–234.
Le-Quôc, K., Le-Quôd, D., and Gaudemer, Y. (1981).Biochemistry 20, 1705–1710.
Lowry, O. H., Rosenbrough, N. J., Farr, A. L., and Randall, R. (1951).J. Biol. Chem. 193, 265–275.
Mowery, P. C., Steekamp, D. J., Ackrell, B. A. C., Singer, T. P., and White, G. A. (1977).Arch. Biochem. Biophys. 178, 495–506.
Richert, D., Vanderlinde, R., and Westerfeld, W. (1950).J. Biol. Chem. 183, 261–274.
Singer, T. P., Kearney, B. E., and Kenney, C. W. (1973).Adv. Enzymol. 5, 189–271.
Vinogradov, A. D., Zimakova, N. I., and Solntseva, T. I. (1971).Dokl. Akad. Nauk. USSR 201, 359–362.
Vinogradov, A. D., Winter, D. W., and King, T. E. (1972).Biochem. Biophys. Res. Commun. 49, 441–444.
Vinogradov, A. D., Gavrikova, E. V., and Zuevsky, V. V. (1976).Eur. J. Biochem. 63, 365–371.
Whereat, A. F., Hull, F. E., Orishimo, M. W., and Rabinowitz, J. (1967).J. Biol. Chem. 242, 4013–4022.
Wojtczak, L., Wojtczak, A. B., and Ernster, L. (1969).Biochim. Biophys. Acta 191, 10–21.
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Jay, D. Inhibition of membrane-bound succinate dehydrogenase by disulfiram. J Bioenerg Biomembr 23, 335–343 (1991). https://doi.org/10.1007/BF00762226
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DOI: https://doi.org/10.1007/BF00762226