Mercapturic Acids as Metabolites of Aromatic Aldehydes and Alcohols

  • F. Seutter-Berlage
  • E. C. Rietveld
  • R. Plate
  • P. J. M. Klippert
Part of the Advances in Experimental Medicine and Biology book series (AEMB)

Summary

After administration of substituted (CH3, OH, OCH3, F, CL, Br, NO2) benzaldehydes or benzyl alcohols in the rat an enhanced urinary thioether excretion was found in some cases.

With p-substituted benzaldehydes only occasionally a slight increase could be shown, but with o-substituted aldehydes and alcohols thioether excretions amounted up to 137 of the dose.

Mercapturic acids were isolated and identified by synthesis, mass-, and n.m.r.-spectrometry as the arylmethyl thioethers of N-acetylcysteine.

Steric hindrance by o-substituents must be the main cause of a relative decrease in oxidation to the carboxylic acid and an increase of the importance of both the reduction of the aldehydes and the reaction of the alcohols, presumably to sulphuric acid esters, as intermediates for the alkylation of glutathione.

Consequently, previous administration of pyrazole, an inhibitor of alcohol dehydrogenase, caused an even larger thioether excretion after injection of o-chlorobenzyl alcohol.

Keywords

Propylene Glycol Benzyl Alcohol Aromatic Aldehyde Ester Sulfate Mercapturic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Boyland, E., and Chasseaud, L.F., 1969, The role of glutathione and glutathione S-transferase in mercapturic acid biosynthesis, Adv. Enzymol., 32: 173.PubMedGoogle Scholar
  2. Chasseaud, L.F., 1979, The role of glutathione and glutathione Stransferases in the metabolism of chemical carcinogens and other electrophillic agents, Adv. Cancer Res., 29: 175.PubMedGoogle Scholar
  3. Clapp, J.J.,and Young, L., 1970, Formation of mercapturic acids in rats after the administration of aralkyl esters, Biochem. J., 118: 765.Google Scholar
  4. De Boer, T.J., and Backer, H.J., 1963, Org. Synth. Coll, Vol. 4: 250.Google Scholar
  5. Furia, T.E., and Bellanca, N., 1975, “Fenaroli’s Handbook of Flavor Ingredients, 2nd ed., Vol. I I, C.R.C. Press, Cleveland, Ohio.Google Scholar
  6. Gilham, B., 1971, The reaction of aralkyl sulphate esters with glutathione catalysed by rat liver preparations, Biochem. J., 121: 667.Google Scholar
  7. Gilham, B., 1973, The mechanism of the reaction between glutathione and 1-menaphthyl sulphate catalysed by a glutathione S-transferase from rat liver, Biochem. J., 135: 797.Google Scholar
  8. Gilham, B., Clapp, J.J., Morrison, A.R. and Young, L., 1970, The interaction of sulphate esters and glutathione in vivo, Biochem. J., 118: 24 P.Google Scholar
  9. Kaye, C.M., 1974, The synthesis of mercapturic acids from diethyl sulphate and di-n-propyl sulphate in the rat, Xenobiotica, 4: 329.PubMedCrossRefGoogle Scholar
  10. Knight, R.H., and Young, L., Biochemical studies of toxic agents II. The occurrence of premercapturic acids, Biochem. J., 70: 111.Google Scholar
  11. Law, G.L., Mansfield, G.P., Muggleton, D.F., and Parnell, E.W., 1963, Dimetridazole: absorption, excretion and metabolism in turkeys, Nature, 197: 1024.CrossRefGoogle Scholar
  12. Roy, B.A., 1971, Sulphate conjugation enzymes, in: “Handbook of Exp. Pharmacology, Vol. 28II, B.B. Brodie and J.R. Gilette, eds., Springer Verlag, Berlin.Google Scholar
  13. Seutter-Berlage, F., Delbressine, L.P.C., Smeets, F.L.M., and Ketelaars, H.C.J., 1978, Identification of three sulphur-containing urinary metabolites of styrene in the rat, Xenobiotica, 8: 413.PubMedCrossRefGoogle Scholar
  14. Seutter-Berlage, F., van Dorp, H.L., Kosse, H.J.J., Hoog Antink, J.M.T., and Wagenaars-Zegers, M.A.P., 1979, The estimation of mercapturic acids and other thioethers in urine, in: “Chemical Porphyria in Man”, J.J.T.W.A. Strik and J.H. Koeman, eds., Elsevier/North-Holland Bianedical Press, Amsterdam.Google Scholar
  15. Shiobara, Y., 1977, The effect of carboxyl substituent on the metabolism of aromatic aldehydes, Xenobiotica, 7: 457.PubMedCrossRefGoogle Scholar
  16. Strand, L.P., and Sheline, R.R., 1975, The metabolism of vanillin and isovanillin in the rat, Xenobiotica, 5: 49.PubMedCrossRefGoogle Scholar
  17. Turk, J.L., and Parker, D., 1978, Interaction of haptens with proteins and their immunogenicity, in: “Immunochemistry”, L.E. Glynn and M.W. Steward, eds., Wiley & Sons, Chichester.Google Scholar
  18. Vestermark, A., and Boström, H., 1959, Studies on ester sulfates V. On the enzymatic formation of ester sulfates of primary aliphatic alcohols, Exp. Cell Res., 18: 174.PubMedCrossRefGoogle Scholar
  19. Vestermark, A., and Boström, H., 1960, On the enzymatic formation of aliphatic polyols, Acta Chem. Scand., 13: 2133.CrossRefGoogle Scholar
  20. Vogel, A.I., 1972, “A Textbook of Practical Organic Chemistry”, 3rd ed., Longman, London.Google Scholar
  21. Williams, R.T., 1959, “Detoxication mechanisms”, 2nd ed., Chapman and Hall, London.Google Scholar
  22. Wong, K.P., and Sourkes, T.L., 1966, Metabolism of vanillin and related substances in the rat, Can. J. Biochem. Physiol., 44: 635.Google Scholar
  23. Wood, J.L., 1970, Biochemistry of mercapturic acid formation, in: “Metabolic conjugation and metabolic hydrolysis”, Vol. II, W.H. Fishman, ed., Academic Press, New York.Google Scholar
  24. Woodman, J., and Young, L., 1971, Mercapturic acid formation from sodium alkyl sulphates in the rat, Biochem. J., 125: 78 P.Google Scholar

Copyright information

© Springer Science+Business Media New York 1982

Authors and Affiliations

  • F. Seutter-Berlage
    • 1
  • E. C. Rietveld
    • 1
  • R. Plate
    • 1
  • P. J. M. Klippert
    • 1
  1. 1.Department of PharmacologyUniversity of NijmegenNijmegenThe Netherlands

Personalised recommendations