Erythrocyte glutathione transferase: a potential new biomarker in chronic kidney diseases which correlates with plasma homocysteine.

The erythrocyte glutathione S-transferase (e-GST) is a member of a superfamily of inducible enzymes involved in cell detoxification that shows an increased expression in chronic kidney disease (CKD) patients. We propose a new automated analysis procedure for e-GST activity that has been validated in 72 CKD patients and 62 maintenance hemodialysis patients (MHD). Regression analysis was carried out to assess association between e-GST activity data, main clinical variables, and plasma homocysteine (Hcy), a modified sulfur amino acid known as potential risk factor for cardiovascular disease that is increased above normal levels in more than 90% of the uremic patients.

The extended catalysis of glutathione transferase.

Glutathione transferase reaches 0.5-0.8 mM concentration in the cell so it works in vivo under the unusual conditions of, [S]≪[E].

Trypanothione efficiently intercepts nitric oxide as a harmless iron complex in trypanosomatid parasites.

Trypanosomatids are protozoan organisms that cause serious diseases, including African sleeping sickness, Chagas' disease, and leishmaniasis, affecting about 30 million people in the world. These parasites contain the unusual dithiol trypanothione [T(SH)(2)] instead of glutathione (GSH) as the main intracellular reductant, and they have replaced the otherwise ubiquitous GSH/glutathione reductase redox couple with a T(SH)(2)/trypanothione reductase (TR) system. The reason for the existence of T(SH)(2) in parasitic organisms has remained an enigma.

Tetramerization and cooperativity in Plasmodium falciparum glutathione S-transferase are mediated by atypic loop 113-119.

Glutathione S-transferase of Plasmodium falciparum (PfGST) displays a peculiar dimer to tetramer transition that causes full enzyme inactivation and loss of its ability to sequester parasitotoxic hemin. Furthermore, binding of hemin is modulated by a cooperative mechanism. Site-directed mutagenesis, steady-state kinetic experiments, and fluorescence anisotropy have been used to verify the possible involvement of loop 113-119 in the tetramerization process and in the cooperative phenomenon.

Glutathione transferases sequester toxic dinitrosyl-iron complexes in cells. A protection mechanism against excess nitric oxide.

It is now well established that exposure of cells and tissues to nitric oxide leads to the formation of a dinitrosyl-iron complex bound to intracellular proteins, but little is known about how the complex is formed, the identity of the proteins, and the physiological role of this process. By using EPR spectroscopy and enzyme activity measurements to study the mechanism in hepatocytes, we here identify the complex as a dinitrosyl-diglutathionyl-iron complex (DNDGIC) bound to Alpha class glutathione S-transferases (GSTs) with extraordinary high affinity (K(D) = 10(-10) m). This complex is formed spontaneously through NO-mediated extraction of iron from ferritin and transferrin, in a reaction that requires only glutathione.

Electrostatic association of glutathione transferase to the nuclear membrane. Evidence of an enzyme defense barrier at the nuclear envelope.

The possible nuclear compartmentalization of glutathione S-transferase (GST) isoenzymes has been the subject of contradictory reports. The discovery that the dinitrosyl-diglutathionyl-iron complex binds tightly to Alpha class GSTs in rat hepatocytes and that a significant part of the bound complex is also associated with the nuclear fraction (Pedersen, J. Z.