Hereditary Absence of Reduced Glutathione in the Erythrocytes — a New Clinical and Biochemical Entity?

Oort, M.; Loos, J.A.; Prins, Hilco

doi:10.1111/j.1423-0410.1961.tb03178.x

Cited by 96 publications

(20 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is of interest that a number of patients have been reported to have erythrocyte glutathione synthetase deficiency associated with decreased erythrocyte glutathione concentrations and compensated hemolytic disease (23)(24)(25)(26)(27). The published information does not indicate the occurrence of serious neonatal morbidity, nor are there published data relating to the presence of acidosis or 5-oxoprolinuria.…”

Section: Discussionmentioning

confidence: 90%

Glutathione Synthetase Deficiency, an Inborn Error of Metabolism Involving the γ-Glutamyl Cycle in Patients with 5-Oxoprolinuria (Pyroglutamic Aciduria)

Wellner

Sekura

Meister

et al. 1974

Proc. Natl. Acad. Sci. U.S.A.

135

View full text Add to dashboard Cite

Enzyme studies on placenta, cultured skin fibroblasts, and erythrocytes from two sisters with the inborn error 5-oxoprolinuria (pyroglutamic aciduria) indicate that the metabolic lesion in this disease is at the glutathione syntbetase (EC 6.3.2.3) step of the 7y-glutamyl cycle. Excessive urinary excretion of 5-oxoproline by these patients appears to be associated with increased synthesis of -y-glutamyl-cysteine and formation of 5-oxoproline from this dipeptide. Thus, 5-oxoproline is produced in amounts that exceed the normal capacity of 5-oxoprolinase to convert it to glutamate. The data indicate that it may be possible to identify individuals who are heterozygous for this trait by determinations of erythrocyte glutathione synthetase.Previous studies on glutathione have indicated that its synthesis and utilization are integrated in a series of enzymecatalyzed reactions, which have been termed the y-glutamyl cycle. The y-glutamyl cycle consists of six enzyme-catalyzed reactions ( Fig. 1): amino acid-dependent breakdown of glutathione to yield y-glutamyl amino acid and cysteinyl-glycine catalyzed by -y-glutamyl transpeptidase (EC 2.3.2.2) conversion of -y-glutamyl amino acid to 5-oxoproline4 and the corresponding free amino acid catalyzed by 'y-glutamyl cyclotransferase (EC 2.3.2.4), enzymatic hydrolysis of cysteinylglycine to cysteine and glycine, conversion of 5-oxoproline to glutamate catalyzed by 5-oxoprolinase, and the two-step synthesis of glutathione from glutamate, cysteine, and glycine catalyzed by -y-glutamyl-cysteine synthetase (EC 6.3.2.2) and glutathione (GSH) synthetase (EC 6.3.2.3). The evidence for the existence of the cycle and for its involvement in amino-acid transport has been reviewed recently (1-3). §In 1970 Jellum et al. (5) reported on an interesting patient who had a massive urinary excretion of 5-oxoproline (about 30 g/day compared to less than a few mg/day in normal individuals).f This patient was a 19-year-old male with metabolic acidosis and multiple neurological symptoms such as mental retardation, spastic tetraparesis, and ataxia. The patient was at first thought to have a defect in the urea cycle (5), but subsequent studies (7-10) have indicated a lesion in the y-glutamyl cycle, although the exact location was not determined.A (12). Since 1 year of age she is known to have excreted in the urine more than 6 g of 5-oxoproline per day, and her plasma concentration of 5-oxoproline has been 2-5 mM (11,12). Studies in which this patient was given [14C]5-oxoproline are consistent with the conclusion that about 25% of the amount of 5-oxoproline formed by this patient is excreted and that the rernainder is metabolized (11); a similar conclusion may now be drawn from the studies done on the first patient (8).Studies on the peripheral leukocytes of the second patient have indicated the presence of 5-oxoprolinase (11). The young girl with 5-oxoprolinuria has recently acquired a sister who suffers from the same inborn error of metabclism (12). 13oth patients, in addition to increased co...

show abstract

Section: Discussionmentioning

confidence: 90%

Glutathione Synthetase Deficiency, an Inborn Error of Metabolism Involving the γ-Glutamyl Cycle in Patients with 5-Oxoprolinuria (Pyroglutamic Aciduria)

Wellner

Sekura

Meister

et al. 1974

Proc. Natl. Acad. Sci. U.S.A.

135

View full text Add to dashboard Cite

show abstract

“…Hereditary hemolytic disorder associated with reduced glutathione deficiency has been reported in 6 different families in Holland [16,19], Germany [12,23], France [3] and USA [15] (table 111). Combined with stomatocytosis it has been described in one case by M iller et al in USA [14] (table IV).…”

Section: Discussionmentioning

confidence: 99%

Hemolytic Anemia Associated with Decreased Concentration of Reduced Glutathione in Red Cells

Lo¹,

Marti²,

Hitzig³

1971

Acta Haematol

View full text Add to dashboard Cite

Three cases of hemolytic anemia with decreased concentration of reduced glutathione in red cells are described. They all have had signs of hyperhemolysis from early infancy and 2 exchange-transfusions had to be performed in one of them. In 2 of them stomatocytes are present in their blood smears and in one of them high sodium and low potassium in the erythrocytes is observed. Family studies reveal several apparently healthy members with the same deficiency and presenting evidence of mild to moderate hyperhemolysis. Genetic transmission was dominant-autosomal. The phenotypic expression seems to differ greatly. In 1 case who presented with gallstones at the age of 19 years splenectomy beneficially influenced the intensity of the hemolytic process.

show abstract

“…It is unlikely that a resultant GSH de-ficiency alone can cause major shortening of erythrocyte survival since almost complete selective inhibition of intracellular erythrocyte GSH with N-ethylmaleimide does not seriously impair erythrocyte survival (24). Also, a hereditary absence of GSH is associated with only a mild hemolytic state (25).…”

Section: Effect Of Chromate-induced Gssg-r Deficiencymentioning

confidence: 99%

Studies on Chromated Erythrocytes. Effect of Sodium Chromate on Erythrocyte Glutathione Reductase*

Koutras¹,

Hattori²,

Schneider³

et al. 1964

J. Clin. Invest.

View full text Add to dashboard Cite

The marked affinity of erythrocytes for hexavalent chromate anion was reported in 1950 by Gray and Sterling (1). Since then, erythrocytes labeled with radioactive sodium chromate have been used extensively for the determination of erythrocyte survival in vivo (1-5) and the determination of blood volume (4-6). The anionic hexavalent form of chromium is bound firmly to erythrocytes, is not reutilized, and is excreted mainly in the urine (2). Gray and Sterling suggested that the hexavalent form of chromium in the erythrocyte is probably bound to hemoglobin. Recent work, however, has shown that not all of the chromium is attached to hemoglobin, but that some of it is combined with a substance of low molecular weight, possibly glutathione (7).Ebaugh, Emerson, and Ross (2) showed that small amounts of chromate, up to 9.5 Fg of chromium per ml of blood, had no apparent effect on the survival of erythrocytes in vivo. When 35 pg per ml of blood was used, however, there was significant hemolysis in vivo during the first 24 hours. Donohue and associates (5) found that amounts below 25 ug of chromium per ml of erythrocytes did not affect erythrocyte survival, but that larger amounts were toxic. In this paper we report the results of studies of the effect of chromate on erythrocyte enzymes. A marked inhibition of glutathione-reductase (GSSG-R) activity was observed. Upon incubation with acetylphenylhydrazine, chromatetreated erythrocytes had an increased tendency to form Heinz bodies, and there was some decrease in glutathione stability.

show abstract

Hereditary Absence of Reduced Glutathione in the Erythrocytes — a New Clinical and Biochemical Entity?

Cited by 96 publications

References 3 publications

Glutathione Synthetase Deficiency, an Inborn Error of Metabolism Involving the γ-Glutamyl Cycle in Patients with 5-Oxoprolinuria (Pyroglutamic Aciduria)

Glutathione Synthetase Deficiency, an Inborn Error of Metabolism Involving the γ-Glutamyl Cycle in Patients with 5-Oxoprolinuria (Pyroglutamic Aciduria)

Hemolytic Anemia Associated with Decreased Concentration of Reduced Glutathione in Red Cells

Studies on Chromated Erythrocytes. Effect of Sodium Chromate on Erythrocyte Glutathione Reductase*

Contact Info

Product

Resources

About