Neurochemical Pathology

, Volume 1, Issue 3, pp 179–191 | Cite as

In vitro and in vivo inhibition of glycolytic enzymes by acrylamide

  • Mohammad I. Sabri
Original Articles


The effect of acrylamide on glyceraldehyde-3-phosphate dehydrogenase, phosphofructokinase, and lactate dehydrogenase has been studied both in vitro and in vivo. Acrylamide inhibited crystalline GAPDH and PFK from rabbit muscle as well as the enzyme present in rat brain and sciatic nerve homogenates in vitro. Inhibition of enzyme activity was a function of the concentration and the duration of preincubation with acrylamide. Enzyme inhibition was prevented by dithiothreitol. Acrylamide did not inhibit LDH activity even at high concentrations. Rats intoxicated with acrylamide had approximately 33% less GAPDH in sciatic nerves, but normal levels were found in liver and brain homogenates. The significance of selective GAPDH inhibition is discussed in relation to the pathogenesis of peripheral neuropathy induced by acrylamide.

Index Entries

Acrylamide, inhibition of glycolytic enzymes by glycolysis, inhibition by acrylamide glycolytic enzymes, inhibition by acrylamide peripheral neuropathy, and acrylamide glyceraldehyde-3-phosphate dehydrogenase, effect of acrylamide on lactic dehydrogenase, effect of acrylamide on phosphofructokinase, effect of acrylamide on 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Chretien M., Patey G., Souyri F., and Droz, B. (1981) Acrylamide-induced neuropathy and impairment of axonal transport of proteins. II. Abnormal accumulation of smooth endoplasmic reticulum at sites of focal retention of fast transported proteins. Electron microscope radioautographic study.Brain Res. 205, 15–28.PubMedCrossRefGoogle Scholar
  2. Dixit R., Mukhtar H., Seth P.K. and Krishna Murti, C.R. (1980a) Binding of acrylamide with glutathione-S-transferases.Chem. Biol. Interactions 32, 353–359.CrossRefGoogle Scholar
  3. Dixit R., Seth P.K., and Mukhtar H. (1980b). Brain glutathione-S-transferase-catalyzed conjugation of acrylamide: a novel mechanism for detoxification of neurotoxin.Biochem. Internat. 1, 547–552.Google Scholar
  4. Dixit R., Husain R., Mukhtar H., and Seth P.K. (1981b) Acrylamide-induced inhibition of hepatic glutathione-S-transferase activity in rats.Toxicol. Lett. 7, 207–210.PubMedCrossRefGoogle Scholar
  5. Dixit R., Mukhtar H., and Seth, P.K. (1981a).In vitro inhibition of alcohol dehydrogenase by acrylamide: Interaction with enzyme— SH groups.Toxicol. Lett. 7, 487–492.PubMedCrossRefGoogle Scholar
  6. Fullerton P. and Barnes J. (1966) Peripheral neuropathy in rats produced by acrylamide.Brit. Indust. Med. 23, 210–221.Google Scholar
  7. Hashimoto K. and Aldridge W.N. (1970). Biochemical studies on acrylamide, a neurotoxic agent.Biochem. Pharmacol. 19, 2591–2609.PubMedCrossRefGoogle Scholar
  8. Howland R.D. (1981) The etiology of acrylamide neuropathy: Enolase, phosphofructokinase, and glyceraldehyde-3-phosphate dehydrogenase activities in peripheral nerve, spinal cord brain and skeletal muscle of acrylamide-intoxicated cats.Toxicol. Appl. Pharmacol. 60, 324–333.PubMedCrossRefGoogle Scholar
  9. Howland R.D., Vyas I.L., and Lowndes H.E. (1980a) The etiology of acrylamide neuropathy: Possible involvement of neuron specific enolase.Brain Res. 190, 529–535.PubMedCrossRefGoogle Scholar
  10. Howland R.D., Vyas I.L., Lowndes H.E., and Argentieri T.M. (1980b). The etiology of toxic peripheral neuropathies:In vitro effects of acrylamide and 2,5-hexanedione on brain enolase and other glycolytic enzymes.Brain Res. 202, 131–142.PubMedGoogle Scholar
  11. Jacobsen, J. and Sidenius P. (1983) Early and dose dependent decrease of retrograde axonal transport in acrylamide intoxicated rats.J. Neurochem. 40, 447–454.CrossRefGoogle Scholar
  12. Ling K.H., Paetkau V., Marcus F., and Lardy H.A. (1966) Phosphofructokinase, in:Methods in Enzymology (Colowick S.P. and Kaplan N.O. eds.), Vol. IX, pp. 425–429, Academic Press, New York.Google Scholar
  13. Lowry O.H., Rosebrough N.J., Farr A.L., and Randall R.J. (1951) Protein measurements with the Folin phenol reagent.J. Biol. Chem. 193, 265–275.PubMedGoogle Scholar
  14. Miller M.J., Carter D.E., and Sipes, I.G. (1982) Pharmacokinetics of acrylamide in Fisher-334 rats.Toxicol. Appl. Pharmacol.,63, 36–46.PubMedCrossRefGoogle Scholar
  15. Poole C.F., Zlatkis W.F., and Spencer, P.S. (1981) Determination of acrylamide in nerve tissue homogenates by electron capture gas chromatography.J. Chrom. 217, 239–243.CrossRefGoogle Scholar
  16. Pleasure D.E., Mishler K.C., and Engel W.K. (1969) Axonal transport of proteins in experimental neuropathies.Science 166, 524–525.PubMedCrossRefGoogle Scholar
  17. Prineas J. (1969) The pathogenesis of dying-back polyneuropathies. II. An ultrastructural study of experimental acrylamide intoxication in the cat.J. Neuropathol. Exp. Neurol. 28, 598–621.PubMedCrossRefGoogle Scholar
  18. Rasool C.G. and Bradley W.G. (1978) Studies on axoplasmic transport of individual proteins: I. Acetyl cholinesterase (AChE) in acrylamide neuropathy.J. Neurochem. 31, 419–425.PubMedCrossRefGoogle Scholar
  19. Ross S.M., Sabri M.I., and Spencer P.S. (1983a) Glyceraldehyde-3-phosphate dehydrogenase in degenerated cat peripheral nerve during acrylamide intoxication.Toxicologist 3, 62.Google Scholar
  20. Ross S.M., Sabri M.I., and Spencer P.S. (1983b) Acrylamide inhibition of nerve glycolytic enzymesin vivo andin vitro.Toxicologist 3, 63.Google Scholar
  21. Sabri M.I. (1983)In vitro effect ofn-hexane and its metabolites on selected enzymes in glycolysis, pentose phosphate pathway and citric acid cycle.Brain Res. (in press).Google Scholar
  22. Sabri M.I. and Ochs S. (1971). Inhibition of glyceraldehyde-3-phosphate dehydrogenase in mammalian nerve by iodoacetic acid.J. Neurochem. 18, 1509–1514.PubMedCrossRefGoogle Scholar
  23. Sabri M.I. and Ochs S. (1972). Relation of ATP and creatine phosphate to fast axoplasmic transport in mammalian nerve.J. Neurochem. 19, 2821–2828.PubMedCrossRefGoogle Scholar
  24. Sabri M.I. and Spencer P.S. (1979) Inhibition of glycolysis by chemically unrelated industrial neurotoxins which produce polyneuropathy.Proc. Internat. Soc. Neurochem. 7th Meeting, 564.Google Scholar
  25. Sabri M.I. and Spencer P.S. (1980a) Inhibition of glyceraldehyde-3-phosphate dehydrogenase and other glycolytic enzymes by acrylamide.Neurosci. Lett. Suppl. 5, 455.Google Scholar
  26. Sabri M.I. and Spencer P.S. (1980b) Toxic distal axonopathy: Biochemical studies and hypothetical mechanisms, inExperimental and Clinical Neurotoxicology (Spencer P.S. and Schaumburg H.H., eds.), pp. 206–219. Williams and Wilkins, Baltimore, Maryland.Google Scholar
  27. Sabri M.I., Dairman W., Juhasz L., Bischoff M.C., and Spencer P.S. (1981) Is acrylamide neurotoxicity pyruvate sensitive?Trans. Am. Soc. Neurochem. 12, 147.Google Scholar
  28. Sabri M.I., Ederle K., Holdsworth C.E., and Spencer P.S. (1979b) Studies on the biochemical basis of distal axonopathies. II. Specific inhibition of fructose-6-phosphate kinase by 2,5-hexanedione and methyln-butyl ketone.Neurotoxicology 1, 285–297.Google Scholar
  29. Sabri M.I., Moore C.L., and Spencer P.S. (1979a) Studies on the biochemical basis of distal axonopathies. I. Inhibition of glycolysis by neurotoxic hexacarbon compounds.J. Neurochem. 32, 683–689.PubMedCrossRefGoogle Scholar
  30. Schaumburg H.H., Wisnieswki H., and Spencer P.S. (1974). Ultrastructural studies of the dying-back process. I. Peripheral nerve terminal axon degeneration in systemic acrylamide intoxication.J. Neuropathol. Exp Neurol. 33, 260–284.PubMedGoogle Scholar
  31. Seth P.K., Dixit R., Mukhtar H., and Parmar, S.S. (1981) Interaction of acrylamide with brain glutathione-S-transferase (GST): A mechanism of its neurotoxicity.Proc. Internat. Soc. Neurochem. 8th Meeting, 424.Google Scholar
  32. Sharma R.P. and Obersteiner E.J. (1977) Acrylamide cytotoxicity in chick ganglia cultures.Toxicol. Appl. Pharmacol. 42, 149–156.PubMedCrossRefGoogle Scholar
  33. Souyri F., Chretien M., and Droz B. (1981). Acrylamide-induced neuropathy and impairment of axonal transport of proteins. I. Multifocal retention of fast transported proteins at the periphery of axons as revealed by light microscope radioautography.Brain Res. 205, 1–13.PubMedCrossRefGoogle Scholar
  34. Spencer P.S. and Schaumburg H.H. (1977a) Ultrastructural studies of the dying-back process. III. The evolution of experimental peripheral giant axonal disease.J. Neuropathol. Exp. Neurol. 36, 276–299.PubMedGoogle Scholar
  35. Spencer P.S. and Schaumburg H.H. (1977b) Ultrastructural studies of the dying-back process. IV. Differential vulnerability of selected PNS and CNS fibers in experimental distal axonopathies.J. Neuropathol. Exp. Neurol. 36, 300–320.PubMedGoogle Scholar
  36. Spencer P.S. and Schaumburg H.H. (1978) The pathology of neurotoxic axonal degeneration, inPhysiology and Pathobiology of Axons (Waxman S., ed.), pp. 265–282. Raven Press, New York.Google Scholar
  37. Spencer P.S., Sabri M.I., Schaumburg H.H., and Moore, C.L. (1979) Does a defect of energy metabolism in the nerve fiber underlie axonal degeneration in polyneuropathies?Ann. Neurol. 5, 501–507.PubMedCrossRefGoogle Scholar
  38. Stolzenbach F. (1966) Lactic dehydrogenase, inMethods in Enzymology (Colowick S.P. and Kaplan N.O., eds.), Vol. IX, pp. 278–283. Academic Press, New York.Google Scholar
  39. Webb J.L. (1966) Enzymes and metabolic inhibitors. Vol. III, p. 811. Academic Press, New York.Google Scholar
  40. Weir R.L., Galubiger G., and Chase T.N. (1978). Inhibition of fast axoplasmic transport by acrylamide.Environ. Res. 17, 251–255.PubMedCrossRefGoogle Scholar

Copyright information

© The Humana Press Inc. 1983

Authors and Affiliations

  • Mohammad I. Sabri
    • 1
  1. 1.Institute of Neurotoxicology, Departments of Neurology and NeuroscienceAlbert Einstein College of MedicineBronxUSA

Personalised recommendations