5-Oxoprolinuria: Biochemical observations and case report

Spielberg, Stephen P.; Kramer, Lloyd I.; Goodman, Stephen I.; Butler, J D; Tietze, Frank; Quinn, Patricia O.; Schulman, Joseph D.

doi:10.1016/s0022-3476(77)80819-6

Cited by 48 publications

(17 citation statements)

References 17 publications

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“…Lymphocytes from a patient with glutathione synthetase deficiency with 5-oxoprolinuria were compared with cells from several normal controls. The patient has been described in detail elsewhere (13,14). His Incubation conditions.…”

Section: Methodsmentioning

confidence: 99%

Nitrofurantoin cytotoxicity. In vitro assessment of risk based on glutathione metabolism.

Spielberg¹,

Gordon²

1981

J. Clin. Invest.

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A B S T R A C T Nitrofurantoin, a commonly used urinary tract antiseptic, has been associated with idiosyncratic pulmonary and hepatic damage. We have used human lymphocytes in vitro to explore the biochemical basis of susceptibility to nitrofurantoin toxicity. The drug itself did not damage the cells as assessed by trypan blue dye exclusion. In the presence of a mouse hepatic microsomal drug-activating system, however, nitrofurantoin metabolites produced dose-dependent toxicity to the lymphocytes. Inhibition of the enzyme epoxide hydrolase did not enhance toxicity; the metabolite thus does not appear to be a furan epoxide. Binding of reactive metabolites to cell macromolecules may lead directly to cell death, or in vivo, by acting as haptens to secondary immunologic responses. The metabolite caused a dosedependent depletion of lymphocyte glutathione content. Cells from a patient with glutathione synthetase deficiency showed markedly enhanced nitrofurantoin toxicity. The findings suggest that glutathione plays a major role in protecting cells from nitrofurantoin-induced damage, and that studies of lymphocyte toxicity and glutathione metabolism in

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Section: Methodsmentioning

confidence: 99%

Nitrofurantoin cytotoxicity. In vitro assessment of risk based on glutathione metabolism.

Spielberg¹,

Gordon²

1981

J. Clin. Invest.

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“…In addition to oxoprolinuric and nonoxoprolinuric forms of the disorder, we previously reported quantitatively different abnormal apparent enzyme affinities for glycine in two patients with oxoprolinuria (6). There are data which suggest the possibility of isozymic forms of glutathione synthetase in erythrocytes and nucleated cells.2 It is possible that other patients may present with abnormalities of one isozymic form of the enzyme leading to further heterogeneity among the oxoprolinuric and nonoxoprolinuric forms of glutathione synthetase deficiency.…”

Section: Resultsmentioning

confidence: 95%

“…Two different human syndromes are associated with decreased activity of erythrocyte glutathione synthetase (EC 6.3.2.3), one presenting in the newborn period with massive 5-oxoprolinuria (pyroglutamic aciduria), metabolic acidosis, and hemolytic anemia (1)(2)(3)(4)(5)(6), and the other at varying ages with isolated hemolytic anemia (7)(8)(9). In oxoprolinuria, erythrocytes, leukocytes, and cultured skin fibroblasts all have been shown to 27 December 1977. glutathione content (4,6).…”

Section: Introductionmentioning

confidence: 99%

“…In oxoprolinuria, erythrocytes, leukocytes, and cultured skin fibroblasts all have been shown to 27 December 1977. glutathione content (4,6). The low intracellular glutathione concentration may reduce feedback inhibition of y-glutamyl-cysteine synthetase (EC 6.3.2.2) with overproduction of 5-oxoproline from y-glutamyl-cysteine (3,10,11).…”

Section: Introductionmentioning

confidence: 99%

“…Y.). Cells were obtained from an oxoprolinuric patient reported by Spielberg et al (6) and from a nonoxoprolinuric patient studied by Mohler et al (9). Assays were performed on confluent cells.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Biochemical heterogeneity in glutathione synthetase deficiency.

Spielberg¹,

Garrick²,

Corash³

et al. 1978

J. Clin. Invest.

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Prenatal diagnosis of glutathione synthase deficiency

Manning

Davies²,

Olpin³

et al. 1994

Prenatal Diagnosis

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Prenatal diagnosis for glutathione synthase (EC 6.3.2.3) deficiency in two pregnancies of an at-risk couple was performed on amniotic fluid taken at 16 weeks' gestation. 5-Oxoproline (pyroglutamic acid) levels were 970 and 790 mumol/l compared with the normal mean value of 29 mumol/l (range 13-51 mumol/l). The pregnancies were terminated and the diagnosis in one case was subsequently confirmed by assay of glutathione synthase in cultured fetal fibroblasts. In the other, post-mortem tissue samples failed to grow.

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5-Oxoprolinuria: Biochemical observations and case report

Cited by 48 publications

References 17 publications

Nitrofurantoin cytotoxicity. In vitro assessment of risk based on glutathione metabolism.

Nitrofurantoin cytotoxicity. In vitro assessment of risk based on glutathione metabolism.

Biochemical heterogeneity in glutathione synthetase deficiency.

Prenatal diagnosis of glutathione synthase deficiency

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