Enhancement of glutathione content in glutathione synthetase-deficient fibroblasts from a patient with 5-oxoprolinuria via metabolic cooperation with normal fibroblasts

Experimental Cell Research
T J KavanaghD L Eaton


Fibroblasts from patients with the disease 5-oxoprolinuria have reduced glutathione synthetase activity and are thus glutathione (GSH) deficient. In this study, 5-oxoprolinuria fibroblasts (GM3877 cells) contained less GSH than normal diploid fibroblasts as determined by biochemical analysis and by flow cytometry using monochlorobimane. They also contained lower gamma-glutamylcysteine synthetase activity than normal cells. However, cocultures of GM3877 cells and normal cells displayed either normal or slightly elevated GSH content, depending upon the assay used. When differentially labeled with fluorescent beads, cocultured, and then isolated by fluorescence-activated cell sorting, both GM3877 cells and normal cells had GSH content similar to that of sorted normal cells cultured alone, whereas sorted GM3877 cells cultured alone showed depressed GSH content. GM3877 cells had detectable levels of gamma-glutamylcysteine (gamma-GC) when cultured alone, but gamma-GC was undetectable in these cells when they were cocultured with normal cells, indicating that it was efficiently metabolized to GSH by the normal cells. These changes in low-molecular-weight thiols were likely to have been mediated by metabolic cooperation across gap junc...Continue Reading


Nov 1, 1996·Nature Genetics·Z Z ShiM W Lieberman
Apr 29, 2006·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Paula Candida FonsecaLuiz Anastacio Alves
Oct 12, 2002·American Journal of Physiology. Lung Cellular and Molecular Physiology·Michael Koval

Related Concepts

Amino Acid Metabolism, Inherited Disorders
Cell Communication
Glutamate-Cysteine Ligase
Reduced Glutathione
Glutathione Synthase
Gap Junctions

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