The importance and regulation of hepatic glutathione.

Glutathione plays a key role in the liver in detoxification reactions and in regulating the thiol-disulfide status of the cell. Glutathione synthesis is regulated mainly by the availability of precursor cysteine and the concentration of glutathione itself which feeds back to regulate its own synthesis. Degradation of hepatic glutathione is principally regulated by the efflux of reduced and oxidized glutathione into both sinusoidal plasma and bile. In addition, glutathione may be consumed in conjugation reactions. Under conditions of oxidative stress, the liver exports oxidized glutathione into bile in a concentrative fashion, whereas under basal conditions, mainly reduced glutathione is exported into bile and blood. The mechanism of export of reduced glutathione into bile and sinusoidal blood is poorly understood.

[1]  A. Meister,et al.  Glutathione: interorgan translocation, turnover, and metabolism. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[2]  H. Sies,et al.  Hepatic mitochondrial and cytosolic glutathione content and the subcellular distribution of GSH‐S‐transferases , 1979, FEBS letters.

[3]  F. Binkley,et al.  Glutathione dependent control of protein disulfide-sulfhydryl content by subcellular fractions of hepatic tissue. , 1977, Biochimica et biophysica acta.

[4]  E. Kosower,et al.  The glutathione status of cells. , 1978, International review of cytology.

[5]  H. Krebs,et al.  Maintenance of glutathione content is isolated hepatocyctes. , 1978, The Biochemical journal.

[6]  J. Oliver,et al.  Effects of glutathione-oxidizing agents on microtubule assembly and microtubule-dependent surface properties of human neutrophils , 1976, The Journal of cell biology.

[7]  A. Meister,et al.  Translocation of glutathione from lymphoid cells that have markedly different gamma-glutamyl transpeptidase activities. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[8]  S. Srivastava,et al.  The transport of oxidized glutathione from human erythrocytes. , 1969, The Journal of biological chemistry.

[9]  S. Orrenius,et al.  Metabolism of extracellular glutathione in rat small-intestinal mucosa. , 1980, European journal of biochemistry.

[10]  S. Orrenius,et al.  Metabolic activation and hepatotoxicity. Toxicity of bromobenzene in hepatocytes isolated from phenobarbital-and diethylmaleate-treated rats. , 1978, Archives of biochemistry and biophysics.

[11]  D. J. Reed,et al.  Involvement of the cystathionine pathway in the biosynthesis of glutathione by isolated rat hepatocytes. , 1980, Archives of biochemistry and biophysics.

[12]  H. Sies,et al.  Reduced and oxidized glutathione efflux from liver , 1978, FEBS letters.

[13]  A. Meister,et al.  Glutathione and gamma-glutamyl cycle enzymes in crypt and villus tip cells of rat jejunal mucosa. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[14]  M. Boyd,et al.  Paradoxical effects of cobaltous chloride and salts of other divalent metals on tissue levels of reduced glutathione and microsomal mixed-function oxidase components. , 1978, The Journal of pharmacology and experimental therapeutics.

[15]  A. Meister,et al.  Hydrolysis and transfer reactions catalyzed by gamma-glutamyl transpeptidase; evidence for separate substrate sites and for high affinity of L-cystine. , 1976, Biochemical and biophysical research communications.

[16]  Y. Vaishnav,et al.  The effects of age and glutathione depletion on hepatic glutathione turnover in vivo determined by acetaminophen probe analysis. , 1980, The Journal of pharmacology and experimental therapeutics.

[17]  O. Koch,et al.  Increased biliary glutathione disulfide release in chronically ethanol‐treated rats , 1979, FEBS letters.

[18]  N. Kaplowitz,et al.  Effect of salicylates and phenobarbital on hepatic glutathione in the rat. , 1980, The Journal of pharmacology and experimental therapeutics.

[19]  T. Higashi,et al.  Turnover of Glutathione in Rat Liver , 1978 .

[20]  E. Bueding,et al.  Antimutagenic effects of 2(3)-tert-butyl-4-hydroxyanisole and of antimicrobial agents. , 1978, Cancer research.

[21]  A. Meister,et al.  Glutathione turnover in the kidney; considerations relating to the gamma-glutamyl cycle and the transport of amino acids. , 1974, Proceedings of the National Academy of Sciences of the United States of America.

[22]  A. Meister,et al.  Regulation of gamma-glutamyl-cysteine synthetase by nonallosteric feedback inhibition by glutathione. , 1975, The Journal of biological chemistry.

[23]  E. Beutler,et al.  Glutathione transport by inside-out vesicles from human erythrocytes. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[24]  L. Flohé,et al.  The fate of extracellular glutathione in the rat. , 1978, Biochimica et biophysica acta.

[25]  A. Neuberger,et al.  Quantitative aspects of glycine metabolism in the rabbit. , 1955, The Biochemical journal.

[26]  T. Higashi,et al.  Studies on the regulation of glutathione level in rat liver. , 1974, Journal of biochemistry.

[27]  S. Orrenius,et al.  Characteristics of glutathione biosynthesis by freshly isolated rat kidney cells. , 1980, The Journal of biological chemistry.

[28]  H. Morris,et al.  Glutathione and gamma glutamyl transpeptidase in rat liver during chemical carcinogenesis. , 1976, Journal of the National Cancer Institute.

[29]  C. Waydhas,et al.  Glutathione efflux from perfused rat liver after phenobarbital treatment, during drug oxidations, and in selenium deficiency. , 1978, European journal of biochemistry.

[30]  M. Orłowski,et al.  Metabolism of gamma-glutamyl amino acids and peptides in mouse liver and kidney in vivo. , 1976, European journal of biochemistry.

[31]  A. Meister,et al.  Interaction of gamma-glutamyl transpeptidase with amino acids, dipeptides, and derivatives and analogs of glutathione. , 1974, The Journal of biological chemistry.

[32]  J. Harington,et al.  Assay, purification, properties and mechanism of action of gamma-glutamylcysteine synthetase from the liver of the rat and Xenopus laevis. , 1973, The Biochemical journal.