Role of glutathione in the catheptic hydrolysis of plasma albumin

Libenson, Leon; Jena, Milton

doi:10.1016/s0003-9861(64)80016-3

Cited by 14 publications

(3 citation statements)

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“…However, if the disulphides of albumin were reduced with dithiothreitol and alkylated to prevent reoxidation, GSH or cysteine had no effect. These results and the work of Libenson & Jena (1963, 1964 establish that GSH and other thiols facilitate proteolysis by reducing the disulphide bonds of protein substrates.…”

Section: Discussionmentioning

confidence: 60%

“…Suggestions have been made that the function of thiols in the facilitation of intralysosomal proteolysis may be to reduce substrate disulphides Abbreviation used: GSH, reduced glutathione. (Wollman, 1969;Pisarev & Dumont, 1975;Van Herle et al, 1979), and some evidence for this has been obtained (Libenson & Jena, 1963, 1964Kooistra et al, 1982). This function of GSH and perhaps other cellular thiols appears not to be enzymically mediated (Griffiths & Lloyd, 1979;Kooistra et al, 1982).…”

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confidence: 98%

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Role of thiols, pH and cathepsin D in the lysosomal catabolism of serum albumin

Mego¹

1984

Biochemical Journal

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Attempts were made to assess the role of thiols and to determine the cathepsins involved in the degradation of serum albumin in mouse liver and kidney lysosomes. Unlike cysteine or beta-mercaptoethanol, reduced glutathione (GSH) did not stimulate the degradation of formaldehyde-treated albumin in liver lysosomes, suggesting that the tripeptide did not penetrate the membrane. However, GSH was a much more effective stimulant of proteolysis in kidney lysosomes than was cysteine at low concentrations, and the effect was saturable at 1-2 mM concentrations. Thiols did not stimulate proteolysis in lysosomes when the disulphide bonds of albumin were reduced and alkylated, suggesting that the stimulatory effects were solely due to disulphide-bond reduction in protein substrates. Results obtained with thiols and iodoacetamide suggested that albumins denatured by disulphide-bond reduction and alkylation, disulphide-bond reduction without alkylation, or by treatment with 8 M-urea, were all degraded primarily by cathepsin D in lysosomes, but formaldehyde-denatured albumin was attacked by thiol proteinases. These findings correlated well with studies on the degradation of these proteins by rat liver lysosome (tritosome) extracts. Studies with the proteinase inhibitors leupeptin and pepstatin and the stimulatory effects of thiols in these extracts suggested that formaldehyde-denatured albumin was degraded primarily by the thiol proteinases, but that native albumin or albumins denatured by disulphide-bond reduction or by treatment with 8 M-urea were attacked by cathepsin D. Denaturation of serum albumin by any of the methods used caused a shift in the pH optimum of albumin catabolism by tritosome extracts or by purified cathepsin D from approx. 3-4 to 5-6. These results were discussed in terms of a possible mechanism for the catabolic aspect of serum albumin turnover.

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Section: Discussionmentioning

confidence: 60%

mentioning

confidence: 98%

Role of thiols, pH and cathepsin D in the lysosomal catabolism of serum albumin

Mego¹

1984

Biochemical Journal

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“…The observations on the incorporation of thiols into albumin may thus be of medical significance, since such incorporation appears to alter the stability of the molecule and this may be the first step in its catabolism. Cathepsins will hydrolyse albumin, but only after it has been treated with glutathione (Libenson & Jena 1964). Jeejeebuoy (1965) has noted that labelled Lister albumin is not suitable for survival studies since it has a half-life well below the accepted values.…”

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confidence: 99%