Serum Gamma-Glutamyl Transpeptidase Deficiency

Goodman, Steffie; Mace, John; Pollak, Shlomo

doi:10.1016/s0140-6736(71)90970-6

Cited by 46 publications

(13 citation statements)

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“…The first patient with glutathionuria, briefly reported by O'Daly (1968), has recently been shown also to be ~/-GTP deficient (O'Daly, personal communication), as is the only other case so thr described, the patient thoroughly documented by Goodman et al (1971) and Schulman et al (1975). All three patients are mentally retarded, although three cases are insufficient evidence to decide whether the mental defect and behaviour problems are a result of the enzyme deficiency or coincidental.…”

Section: Discussionmentioning

confidence: 98%

“…Glutathionuria due to ;,-glutamyl transpeptidase (7-glutamyl transferase, EC 2.3.2.2; },-GTP) deficiency has been described in a 33-year-old male with moderate mental retardation (Stanford-Binet IQ 62) but no other noteworthy somatic or psychiatric features (Goodman et al, 1971 ;Schulman et al, 1975). 7-GTP catalyses the transfer of the ?~-glutamyl moiety of glutathione to a number of L-amino acids and peptides.…”

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confidence: 99%

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Glutathionuria: γ‐Glutamyl transpeptidase deficiency

Wright

Stern

Ersser

et al. 1979

J of Inher Metab Disea

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A mentally retarded young woman with severe behaviour problems was found to excrete large amounts of glutathione due to a generalized gamma-glutamyl transpeptidase deficiency. As in the only other case described in detail, plasma levels and renal reabsorption of the amino acids were normal. In the parents' urine, plasma and leukocytes, enzyme activity was normal but in their cultured fibroblasts it was below the minimum for the control range. An autosomal recessive mode of inheritance is suggested. The implications of these findings for possible role of the gamma-glutamyl cycle in amino acid transport are briefly discussed.

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Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

Glutathionuria: γ‐Glutamyl transpeptidase deficiency

Wright

Stern

Ersser

et al. 1979

J of Inher Metab Disea

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“…GGT knockout mice and the human subjects with GGT deficiency or single nucleotide polymorphism (SNP) would be good models for such studies. Fortunately, the human GGT deficiency, which is associated with mental retardation, is apparently very rare and only several cases have been reported (70)(71)(72)(73)(74), while there is no report of SNPs for human GGT so far. Another important aspect for future study is the regulation of GGT genes, especially in humans.…”

Section: Future Perspectivementioning

confidence: 99%

Redox Regulation of γ-Glutamyl Transpeptidase

Zhang

Forman

2009

Am J Respir Cell Mol Biol

137

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g-Glutamyl transpeptidase (GGT) catalyzes the transfer of the glutamyl moiety from glutathione, and glutathione S-conjugates to acceptors to form another amide or to water to produce free glutamate. Functionally, GGT plays important roles in glutathione homeostasis and mercapturic acid metabolism. The expression of GGT is increased as an adaptive response upon the exposure of oxidative stress. The underlying mechanism of this, however, is nebulous, as GGT gene structure is complex and its transcription is usually controlled by multiple promoters that generate several subtypes of GGT mRNAs. Studies reveal that signaling pathways such as Ras, ERK, p38MAPK, and PI3K are involved in the induction of GGT gene expression in response to oxidative stress. Thus, not surprisingly, induction of GGT mRNA subtypes and the involvement of multiple signaling pathways vary depending on cell type and stimuli.

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“…The first evidence for this proposal came from the characterization of a patient who was found to be deficient in 7-glutamyltranspeptidase (72). Deficiency of this enzyme was based on the inability to measure 7-glutamyltranspeptidase activity with a variety of substrates in cultured fibroblasts (72) or in blood (20). The patient exhibited glutathionemia (5-fold increase) and glutathionuria (850 mg/day).…”

Section: Extracellular Degradation Of Glutathionementioning

confidence: 99%

Characterization and Physiological Function of Rat Renal γ-Glutamyltranspeptidase

Curthoys

Hughey²

1979

Enzyme

135

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Rat renal γ-glutamyltranspeptidase is an intrinsic membrane glycoprotein. The larger of its two subunits is apparently folded into two distinguishable domains which are separated by a protease-sensitive sequence of amino acids. Membrane binding of γ-glutamyltranspeptidase results from the hydrophobic interaction of the nonpolar domain of the amphipathic subunit with the lipid bilayer. Localization of at least a portion of the γ-glutamyl binding site on the smaller subunit limits the active site of the enzyme to one side of the membrane. Within the kidney, the enzyme is primarily associated with the luminal surface of the brush border membrane of the proximal straight tubule. Comparison of the kinetic properties of γ-glutamyltranspeptidase with the pH and the substrates available within the tubular fluid suggests that the physiologically significant reaction catalyzed by the transpeptidase is the hydrolysis of glutathione and its S-derivatives. The glutathionemia and glutathionuria observed in a patient who lacks detectable γ-glutamyltranspeptidase activity and in mice following specific inhibition of transpeptidase, support the hypothesis that the enzyme plays a major role in glutathione catabolism. It now appears that the activities attributed to the γ-glutamyl cycle do not participate in amino acid transport, but instead constitute three separate metabolic pathways; the intracellular synthesis of glutathione, the intracellular degradation of γ-glutamyl peptides and the extracellular hydrolysis of glutathione. The finding that various cells release reduced and oxidized glutathione indicates that glutathione turnover may be a process of intracellular synthesis, excretion and extracellular degradation.

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Serum Gamma-Glutamyl Transpeptidase Deficiency

Cited by 46 publications

References 0 publications

Glutathionuria: γ‐Glutamyl transpeptidase deficiency

Glutathionuria: γ‐Glutamyl transpeptidase deficiency

Redox Regulation of γ-Glutamyl Transpeptidase

Characterization and Physiological Function of Rat Renal γ-Glutamyltranspeptidase

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