Reversible conjugation of isothiocyanates with glutathione catalyzed by human glutathione transferases

Biochem Biophys Res Commun. 1995 Jan 17;206(2):748-55. doi: 10.1006/bbrc.1995.1106.

Abstract

Rates were determined for the nonezymatic (second order rate constants) and enzyme-catalyzed conjugations with glutathione of four isothiocyanates that are present in edible plants (allyl-, benzyl-, phenethyl-isothiocyanates, and sulforaphane). Of four cloned human glutathione transferases studied, GSTP1-1 and GSTM1-1 were the most efficient catalysts. GSTA1-1 was less efficient, and GSTM2-2 was the least efficient. Conjugation of benzyl-NCS is the most rapid and that of sulforaphane [CH3S(O)(CH2)4-NCS] is the slowest. The large enzymatic rate enhancements and the abundance of the enzymes suggest that the glutathione transferases play important roles in the metabolic disposition of isothiocyanates in humans. Enzymatic cleavage of the GSH conjugates of isothiocyanates (dithiocarbamates) is catalyzed by glutathione transferases. The importance of these reverse reactions is probably limited because they are slow and inhibited by high intracellular concentrations of glutathione.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Glutathione / chemistry
  • Glutathione / metabolism*
  • Glutathione Transferase / metabolism*
  • Humans
  • Isoenzymes / metabolism
  • Isothiocyanates / chemistry
  • Isothiocyanates / metabolism*
  • Kinetics
  • Plants, Edible
  • Recombinant Proteins / metabolism
  • Structure-Activity Relationship
  • Substrate Specificity

Substances

  • Isoenzymes
  • Isothiocyanates
  • Recombinant Proteins
  • Glutathione Transferase
  • Glutathione