Distribution of oxidized and reduced forms of glutathione and cysteine in rat plasma

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Abstract

The distribution of the glutathionyl moiety between reduced and oxidized forms in rat plasma was markedly different than that for the cysteinyl moiety. Most of the glutathionyl moiety was present as mixed disulfides with cysteine and protein whereas most of the cysteinyl moiety was present as cystine. Seventy percent of total glutathione equivalents was bound to proteins in disulfide linkage. The distribution of glutathione equivalents in the acid-soluble fraction was 28.0% as glutathione, 9.5% as glutathione disulfide, and 62.6% as the mixed disulfide with the cysteinyl moiety. In contrast, 23% of total cysteine equivalents was protein-bound. The distribution of cysteine equivalents in the acid-soluble fraction was 5.9% as cysteine, 83.1% as cystine, and 10.8% as the mixed disulfide with the glutathionyl moiety. A first-order decline in glutathione occurred upon in vitro incubation of plasma and was due to increased formation of mixed disulfides of glutathione with cysteine and protein. This indicates that plasma thiols and disulfides are not at equilibrium, but are in a steady-state maintained in part by transport of these compounds between tissues during the interorgan phase of their metabolism. The large amounts of protein-bound glutathione and cysteine provide substantial buffering which must be considered in analysis of transient changes in glutathione and cysteine. In addition, this buffering may protect against transient thiol-disulfide redox changes which could affect the structure and activity of plasma and plasma membrane proteins.

References (50)

  • L.H. Lash et al.

    Biochem. Biophys. Res. Commun

    (1983)
  • L.H. Lash et al.

    J. Biol. Chem

    (1984)
  • L.H. Lash et al.

    Biochim. Biophys. Acta

    (1984)
  • S.P. Mukherjee et al.

    Biochim. Biophys. Acta

    (1981)
  • D. Häberle et al.

    FEBS Lett

    (1979)
  • A. Wendel et al.

    FEBS Lett

    (1980)
  • M.E. Anderson et al.

    J. Biol. Chem

    (1980)
  • M.E. Anderson et al.

    Biochem. Biophys. Res. Commun

    (1980)
  • J.C. Crawhall et al.

    Amer. J. Med

    (1968)
  • R. Saetre et al.

    Anal. Biochem

    (1978)
  • R.K. Chawla et al.

    Gastroenterology

    (1984)
  • J.D. Finkelstein et al.

    J. Nutr

    (1982)
  • M.H. Malloy et al.

    Anal. Biochem

    (1981)
  • M.H. Malloy et al.

    Amer. J. Clin. Nutr

    (1983)
  • D.J. Reed et al.

    Anal. Biochem

    (1980)
  • L.H. Lash et al.

    Arch. Biochem. Biophys

    (1983)
  • G. Ellman et al.

    Anal. Biochem

    (1979)
  • F. Tietze

    Anal. Biochem

    (1969)
  • L. Hagenfeldt et al.

    Clin. Chim. Acta

    (1978)
  • T.P. King

    J. Biol. Chem

    (1961)
  • N.S. Kosower et al.

    Int. Rev. Cytol

    (1978)
  • E.M. Scott et al.

    J. Biol. Chem

    (1963)
  • T.M. McIntyre et al.

    Int. J. Biochem

    (1980)
  • G.M. Bartoli et al.

    FEBS Lett

    (1978)
  • R. Hahn et al.

    Biochim. Biophys. Acta

    (1978)
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    This study was supported by NIH Grant HL 30286.

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