scholarly journals Probing the Interactions of Sulfur-Containing Histidine Compounds with Human Gamma-Glutamyl Transpeptidase

Marine Drugs ◽  
2019 ◽  
Vol 17 (12) ◽  
pp. 650 ◽  
Author(s):  
Alfonsina Milito ◽  
Mariarita Brancaccio ◽  
Michael Lisurek ◽  
Mariorosario Masullo ◽  
Anna Palumbo ◽  
...  
Keyword(s):  
Redox Homeostasis ◽  
Glutathione Metabolism ◽  
Embryonic Cells ◽  
Gamma Glutamyl Transpeptidase ◽  
Docking Analysis ◽  
Gamma Glutamyl ◽  
A Cell ◽  
Human Use ◽  
Further Development ◽  
Glutamyl Transpeptidase

Gamma-glutamyl transpeptidase (GGT) is a cell surface enzyme involved in glutathione metabolism and maintenance of redox homeostasis. High expression of GGT on tumor cells is associated with an increase of cell proliferation and resistance against chemotherapy. GGT inhibitors that have been evaluated in clinical trials are too toxic for human use. We have previously identified ovothiols, 5(Nπ)-methyl-thiohistidines of marine origin, as non-competitive-like inhibitors of GGT that are more potent than the known GGT inhibitor, 6-diazo-5-oxo-l-norleucine (DON), and are not toxic for human embryonic cells. We extended these studies to the desmethylated form of ovothiol, 5-thiohistidine, and confirmed that this ovothiol derivative also acts as a non-competitive-like GGT inhibitor, with a potency comparable to ovothiol. We also found that both 5-thiohistidine derivatives act as reversible GGT inhibitors compared to the irreversible DON. Finally, we probed the interactions of 5-thiohistidines with GGT by docking analysis and compared them with the 2-thiohistidine ergothioneine, the physiological substrate glutathione, and the DON inhibitor. Overall, our results provide new insight for further development of 5-thiohistidine derivatives as therapeutics for GGT-positive tumors.

scholarly journals Early elevated serum gamma glutamyl transpeptidase after liver transplantation is associated with better survival

F1000Research ◽  
2014 ◽  
Vol 3 ◽  
pp. 85 ◽  
Author(s):  
Edris M Alkozai ◽  
Ton Lisman ◽  
Robert J Porte ◽  
Maarten W Nijsten
Keyword(s):  
Liver Transplantation ◽  
Aspartate Aminotransferase ◽  
Alanine Aminotransferase ◽  
Total Bilirubin ◽  
Elevated Serum ◽  
Glutathione Metabolism ◽  
Gamma Glutamyl Transpeptidase ◽  
Gamma Glutamyl ◽  
Increased Risk ◽  
Glutamyl Transpeptidase

Background: Gamma glutamyl transpeptidase (GGT) is a membrane bound enzyme that plays a key role in the synthesis of the antioxidant glutathione. Epidemiological studies have linked high GGT with an increased risk of morbidity and cardiovascular mortality. In contrast, GGT is usually elevated in liver transplant recipients that experience good outcomes.Aims: To study if and how GGT is correlated with mortality following liver transplantation.Methods: We analyzed the prognostic relevance of serum GGT levels during the early and late postoperative period after liver transplantation in 522 consecutive adults. We also studied alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels.Results: Early after transplantation, the peak median (interquartile range) GGT levels were significantly higher in patients who survived more than 90 days compared to non-survivors: 293 (178-464) vs. 172 (84-239) U/l, p<0.0001. In contrast, late after transplantation, GGT levels were significantly lower in patients who survived more than 5 years than those who did not (p<0.01). The pattern of GGT levels also differed from those of alanine aminotransferase, aspartate aminotransferase, and total bilirubin early after transplantation, while these patterns were congruent late after transplantation. Kaplan-Meier survival analysis showed that early after transplantation the higher the GGT levels, the better the 90-day survival (p<0.001). In contrast, late after transplantation, higher GGT levels were associated with a lower 5-year survival (p<0.001).Conclusions:  These paradoxical findings may be explained by the time-dependent role of GGT in glutathione metabolism. Immediate postoperative elevation of GGT may indicate a physiological systemic response while chronic elevation reflects a pathological response.

Relationship Between Gamma-glutamyl Transpeptidase Activity and Inflammatory Response in Lichen Planus

2018 ◽  
Vol 69 (3) ◽  
pp. 739-743 ◽  
Author(s):  
Madalina Irina Mitran ◽  
Ilinca Nicolae ◽  
Corina Daniela Ene ◽  
Cristina Iulia Mitran ◽  
Clara Matei ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Lichen Planus ◽  
Inflammatory Process ◽  
Molecular Mechanisms ◽  
Functional Adaptation ◽  
Physical Factors ◽  
Inflammatory Disorder ◽  
Gamma Glutamyl Transpeptidase ◽  
Gamma Glutamyl ◽  
Glutamyl Transpeptidase

Chemicals used in the manufacture of synthetic fibers have been associated with undesirable side effects such as itching or skin lesions and it seems that they are involved in the induction of pathological processes such as oxidative stress and inflammation. Lichen planus (LP) can be regarded as an inflammatory disorder, chemical and physical factors playing an important role in the perpetuation of the inflammatory process. Gamma-glutamyl transpeptidase (GGT) plays an important role in the preservation of skin architecture and modulation of skin inflammation. In this study, we found that GGT activity is increased in LP patients with mild inflammation, whilst GGT is inactivated under conditions of severe inflammation. Therefore, GGT is involved in the inflammatory process, but there is no a positive correlation between its activity and the intensity of the inflammatory response. This functional adaptation of the enzyme may be due to down-regulation of its synthesis under free radical overload conditions. Understanding the molecular mechanisms involved in the modulation of intracellular redox homeostasis is an important step in the pharmacological management of patients with LP.

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