Membrane-Bound γ-Glutamyl Transpeptidase

Meister, Alton; Tate, Suresh S.; Ross, Leonard L.

doi:10.1007/978-1-4684-2658-8_13

Cited by 74 publications

(40 citation statements)

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“…Earlier studies on -y-glutamyl transpeptidase have emphasized its localization in epithelial cells (1,2). Thus, the present finding of the enzyme in lymphoid cells, which are of mesenchymal origin, indicates that this enzyme enjoys a broader distribution in mammalian cells than previously recognized.…”

Section: Discussionsupporting

confidence: 54%

“…This membrane-bound enzyme is known to be localized in epithelial cells, for example, those of the intestinal mucosa, proximal renal tubules, ciliary body, and choroid plexus (1,2). Hypotheses concerning the physiological role of this enzyme, such as a function in amino acid transport across epithelial membranes (2)(3)(4)(5), have been based largely on information derived from studies on intact animals or organs and on isolated enzymes; studies on free cell systems have not yet been carried out.…”

mentioning

confidence: 99%

“…In general, the specificities shown in Table 4 closely resemble those observed previously with purified human (19) and rat kidney (6,18) 'y-glutamyl transpeptidases, respectively. L-Serine, in the presence of borate, strongly inhibited the activity of intact cells; such inhibition occurs with -y-glutamyl transpeptidases from other sources (2,20).…”

mentioning

confidence: 99%

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gamma-Glutamyl transpeptidase, a lymphoid cell-surface marker: relationship to blastogenesis, differentiation, and neoplasia.

Novogrodsky¹,

Tate²,

Meister³

1976

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

106

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'y-Glutamyl transpeptidase, an enzyme that catalyzes y-glutamyl transfer from y-glutamyl compounds to amino acid and peptide acceptors, and which is known to be localized in the membranes of many epithelial cells, was found in a variety of lymphoid cells. The lymphoid cell enzyme is located on the cell surface and exhibits substantially the same substrate specificity as the enzyme found in epithelial cells. Lymphocyte Cultures. Human peripheral blood lymphocytes were obtained from normal subjects by the Ficoll-Hypaque method (7). They were further purified from the adhering cells by passing through a nylon-wool column, and the bone marrow-derived (B-) and thymus-derived (T-) cells were separated by the sheep erythrocyte resetting method (8). The lymphoc4ytes which did and did not form rosettes with sheep erythrocytes are referred to as T-lymphocytes and B-lymphocytes, respectively. Mouse (CBA strain; male, 6-12 weeks of age), rat (Sprague-Dawley; male, 250 g), and guinea-pig (strain 13; male, 250 g) lymphocytes were obtained from spleens and lymph nodes as described (9). The erythrocytes were selectively lysed by incubation in a buffer containing 0.15 M NH4Cl, 0.017 M Tris-HCl (pH 7.2) at 00 for 10 min. Mouse, rat, and guinea pig lymphocytes (2 X 106 cells per ml) and human peripheral blood lymphocytes (1 X 106 cells per ml) were cultured in RPMI 1640 medium containing 5% fetal calf serum (heat inactivated) and supplemented with penicillin (100 units/ml) and streptomycin (100 Mug/ml) at 370 in an atmosphere of 95% air-5% CO2.In the [3H]thymidine incorporation studies, aliquots (1 ml) of cell cultures were incubated for 2 hr with [3H]thymidine (2.5 1.Ci) and isotope incorporation into 5% trichloroacetic acidinsoluble material was measured (9).

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Section: Discussionsupporting

confidence: 54%

mentioning

confidence: 99%

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gamma-Glutamyl transpeptidase, a lymphoid cell-surface marker: relationship to blastogenesis, differentiation, and neoplasia.

Novogrodsky¹,

Tate²,

Meister³

1976

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

106

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“…Such a transport mechanism may also be present to some extent in other tissues as well, especially in anatomic locations known to possess relatively high concentrations of y-glutamyl transpeptidase [e.g., choroid plexus (15), ciliary body (16), and jejunum (17,18)]. It seems notable that a low but detectable uptake of -y-glutamylMet(SO2) was found in the liver and pancreas.…”

Section: Discussionmentioning

confidence: 99%

Transport of gamma-glutamyl amino acids: role of glutathione and gamma-glutamyl transpeptidase.

Griffith¹,

Bridges²,

Meister³

1979

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

146

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This work relates to the hypothesis that one of the mechanisms that mediates amino acid translocation across cell membranes involves the action of membrane-bound 'y-glutamyl transpeptidase on intracellular glutathione and extracellular amino acids to form y-glutamyl amino acids. Ac-cording to this idea, the latter are translocated into the cell where the y-glutamyl moiety is removed to yield free amino acids. Previous studies in this laboratory showed that intracellular glutathione is translocated out of many cells. We have now directly examined the transport of 'y-glutamyl amino acids into tissues in the mouse by use of the model substrate L--y-glutamyl-L4[4Cjmethionine sulfone. Of 11 tissues examined, only the kidney showed strong and preferential uptake of the substrate. A substantial amount of the administered L-y-glutamyl-L{14Ctmethionine sulfone was found intact in the kidney; the total uptake of this compound was greater (by about 2-fold) than that of free L-methionine sulfone. Studies with a number of other y-glutamyl amino acids and y-glutamyl compounds indicate that the kidney has a relatively specific transport system for y-glutamyl amino acids. Small but significant amounts of y-glutamylmethionine sulfone were found in the liver and pancreas, suggesting that other tissues may also have this system. Transport of y-glutamylmethionine sulfone into the kidney was inhibited by inhibitors of glutathione synthesis and of y-glutamyl transpeptidase. The results suggest that both the transpeptidase and glutathione may be involved in transport of -y-glutamyl amino acids. Results of recent studies on glutathione metabolism in which the function of the y-glutamyl cycle was studied in vivo are consistent with the idea that the cycle serves as one of the systems that mediates translocation of amino acids across cell membranes (1-5). According to this hypothesis (see ref. 5 for background), amino acids are translocated across the cell membrane as the corresponding y-glutamyl amino acids, which are formed by the action of membrane-bound -y-glutamyl transpeptidase on glutathione and amino acids. Glutathione is predominately intracellular, whereas a major fraction of the cellular y-glutamyl transpeptidase is on the external surface of cell membranes. The finding of an enzyme on one side of a membrane and of its major substrate on the other has been illuminated by the discovery that intracellular glutathione is translocated out of many cells. In vivo studies on mice in which 'y-glutamyl transpeptidase was inhibited by administration of L-or D-'y-glutamyl(o-carboxy)phenylhydrazide and in which glutathione synthesis was inhibited by giving prothionine sulfoximine indicated that translocation of glutathione occurs across cell membranes in kidney and in other organs (3). Studies on human lymphoid cells that have markedly different y-glutamyl transpeptidase activities (6) and on human fibroblasts (7), as well as observations on isolated perfused liver preparations (8), have provided additional evidence for efflux of ...

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“…Introduction yGlutamy1 transpeptidase catalyzes the initial step in the breakdown of glutathione. A proposed role for the enzyme in transport processes [ 1,2] is consistent with its localization in the plasma membranes of a variety of epithelial cells [3,4]. The enzyme is also present in human and rat lymphoid cells and the activity can be increased by treatment of the cells with mitogenic agents [5].…”

mentioning

confidence: 89%