Erythrocyte glutathione synthetase in 5-oxoprolinuria: Kinetic studies of the mutant enzyme and detection of heterozygotes

Larsson, Agne; Zetterström, Rolf; Hörnell, Herje; Porath, U

doi:10.1016/0009-8981(76)90298-9

Cited by 31 publications

(14 citation statements)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on the analysis of survival curves of a cell strain obtained from a patient suffering from 5-oxoprolinuria (Larsson 1981) (P family (Larsson et al 1976)), it was shown that these cells, deficient in glutathione synthetase (GSH-S) and exhibiting a decreased GSH level, were more radiosensitive (dose modifying factor (d.m.f.) = 1-2) than controls when irradiation was performed in air (Deschavanne et al D. Debieu et al 1981 a).…”

Section: Introductionmentioning

confidence: 99%

Survival Curves of Glutathione Synthetase Deficient Human Fibroblasts: Correlation between Radiosensitivity in Hypoxia and Glutathione Synthetase Activity

Debieu¹,

Deschavanne²,

Midander³

et al. 1985

International Journal of Radiation Biology and Related Studies

View full text Add to dashboard Cite

The role of intracellular non-protein bound sulphydryl compounds (NPSH), and in particular that of glutathione (GSH), in the response of cells to ionizing radiation under different O2 concentrations has been assessed using cell strains deficient in glutathione synthetase and exhibiting different NPSH levels. The cell strains used originated from patients with 5-oxoprolinuria and from their relatives (heterozygotes and proficient homozygotes). No correlation has been found between NPSH and GSH concentrations and radiosensitivity under oxic, aerobic and hypoxic conditions. However, a highly significant correlation has been observed between radiosensitivity under hypoxic conditions (and therefore the oxygen enhancement ratio) and the glutathione synthetase activity, suggesting that synthesis of GSH is required after irradiation. In order to explain our results we postulated, beside radical processes, the existence of a GSH-dependent enzymatic repair mechanism for N2 type damage. Hypoxic radio-sensitivity measured with survival curves would result from the interaction of both competition and biochemical repair processes.

show abstract

Section: Introductionmentioning

confidence: 99%

Survival Curves of Glutathione Synthetase Deficient Human Fibroblasts: Correlation between Radiosensitivity in Hypoxia and Glutathione Synthetase Activity

Debieu¹,

Deschavanne²,

Midander³

et al. 1985

International Journal of Radiation Biology and Related Studies

View full text Add to dashboard Cite

show abstract

“…5-Oxoproline was determined in plasma and urine (Hagenfeldt et al, 1974). The total glutathione concentrations in erythrocytes ~ was measured as described (Larsson et al, 1976). The preparation and determination of free and total glutathione and y-glutamylcysteine levels (M~rtensson, 1986, 1987) in leukocytes and plasma were determined by established procedures.…”

Section: Methodsmentioning

confidence: 99%

A therapeutic trial withN‐acetylcysteine in subjects with hereditary glutathione synthetase deficiency (5‐oxoprolinuria)

Mårtensson

Gustafsson

Larsson

1988

J of Inher Metab Disea

View full text Add to dashboard Cite

In a therapeutic trial, the effect of short-term low-dosage N-acetylcysteine supplementation on glutathione metabolism was investigated in two patients with hereditary glutathione deficiency (5-oxoprolinuria). Clinical and neurophysiological examinations of the patients indicated progressive neurological damage. The pretreatment concentrations of total and free glutathione in leukocytes were 15-20% of normal, whereas the corresponding gamma-glutamylcysteine levels were increased. In plasma, the glutathione concentrations were similarly decreased, but no gamma-glutamylcysteine was detected. Total glutathione in erythrocytes was markedly decreased. Low urinary excretion of cysteinylglycine, cyst(e)ine, taurine, N-acetylcysteine, mercaptolactate and mercaptoacetate and reduced leukocyte taurine levels constituted additional evidence of decreased intracellular availability of cysteine, i.e. glutathione. Oral supplementation with N-acetylcysteine (5 mg/kg x 3/day) had no effect on acid-base balance, erythrocyte glutathione levels or 5-oxoproline concentrations in plasma and urine. In leukocytes, the glutathione concentrations were increased by 20-30%, whereas the gamma-glutamylcysteine levels were essentially unaltered. In parallel, the urinary excretion of cysteinylglycine was increased and the leukocyte levels and urinary outputs of sulphur amino acids were restored. No side-effects of the treatment were noted. The results indicate that N-acetylcysteine may be of value in increasing the low intracellular glutathione concentrations and cysteine availability in patients with hereditary glutathione synthetase deficiency.

show abstract

“…However, the usual story is acidosis and/or haemolysis present from the neonatal period which is usually controlled through bicarbonate administration. In one family (Larsson et al, 1976) a post mortem diagnosis was established in a girl after the diagnosis in the younger brother.…”

Section: Case Reportmentioning

confidence: 99%

5‐Oxoprolinuria (glutathione synthetase deficiency): a case with neonatal presentation and rapid fatal outcome

Divry

Roulaud-Parrot

Dorche

et al. 1991

J of Inher Metab Disea

View full text Add to dashboard Cite

Erythrocyte glutathione synthetase in 5-oxoprolinuria: Kinetic studies of the mutant enzyme and detection of heterozygotes

Cited by 31 publications

References 4 publications

Survival Curves of Glutathione Synthetase Deficient Human Fibroblasts: Correlation between Radiosensitivity in Hypoxia and Glutathione Synthetase Activity

Survival Curves of Glutathione Synthetase Deficient Human Fibroblasts: Correlation between Radiosensitivity in Hypoxia and Glutathione Synthetase Activity

A therapeutic trial withN‐acetylcysteine in subjects with hereditary glutathione synthetase deficiency (5‐oxoprolinuria)

5‐Oxoprolinuria (glutathione synthetase deficiency): a case with neonatal presentation and rapid fatal outcome

Contact Info

Product

Resources

About