Structure Of Glutathione Research Articles

Density functional theory study of the antioxidant activity of glutathione: Reaction with alloxan and its derivatives

The reactions of alloxan and its derivatives with glutathione (γ-glutamylcysteinylglycine, GSH), a sulfhydryl (-SH) antioxidant, antitoxin, and enzyme cofactor, were studied using the density functional theory (DFT). The potent reducing power of GSH is responsible for its free-radical scavenging, electron-donating, and sulfhydryl-donating capacities. Alloxan reacts with GSH to produce alloxan AH and glutathione GS radicals. AH reacts with another GSH molecule to produce dialuric acid. The reactions involved in the alloxan-dialuric acid redox cycle with glutathione participation were also investigated. According to our research on the structure of glutathione and its reaction with alloxan, the dissociation of the sulfhydryl group results in the formation of a sulfur-centered radical (HAT mechanism), which is the cause of the scavenging reaction. This reacts with an alloxan radical and either converts it to a dialuric acid anion or forms a complex known as ‘Compound 305′ with it. The calculated redox potentials at physiological pH indicate that one-electron reduction is not thermodynamically possible. Instead, a two-electron reduction occurs, which directly produces a dialuric acid anion. In addition, a systematic study was conducted on alloxan-like substances that do not cause diabetes, to determine the changes in these substances that are responsible for the loss of diabetogenicity. The lipophilicity and electron affinity of alloxan derivatives were found to be inversely correlated, indicating that increasing the chain length of N-substituted derivatives decreased diabetogenicity in both counts. The electron affinity appears to be the most important parameter for determining the diabetogenicity of alloxan-like compounds derived from uric acid.

High-pressure in situ methods revealing the effect of pressure on glutathione structure

High-pressure processing is a nonthermal method of food processing that is widely used in sterilization and enzyme inactivation. Although some works on technological parameters and quality evaluation have been performed, the mechanism of high pressure on food is still unclear. Due to the complexity of food ingredients, a tremendously important tripeptide in food proteins, orthorhombic l-glutathione, was employed in this work. In addition, in situ methods such as high-pressure Raman, infrared, and X-ray diffraction were used to investigate the structural changes in the pressure range of 0–10 GPa. Experimental results showed that the sample underwent two phase transitions in pressure intervals of 1.8–2.2 and 4.1–5.3 GPa. In addition, the strength of the hydrogen bonds (NH⋯O; OH⋯O; SH⋯O; CH⋯O) also changed in the two pressure intervals. This work may have potential research value for revealing the mechanism of high-pressure processing on food proteins.

Gamma-glutamyltransferases: exploring the complexity of a multi-functional family of enzymes

Gamma-glutamyltransferases: exploring the complexity of a multi-functional family of enzymes

Chemical and cellular antioxidant activity of two novel peptides designed based on glutathione structure

Two novel peptides, ECH (Glu-Cys-His) and YECG (Tyr-Glu-Cys-Gly), were designed based on glutathione (Glu-Cys-Gly, GSH) and their antioxidant activities were studied. Various chemical methods based on single-electron-transfer (SET) and hydrogen-atom-transfer (HAT) were applied to evaluate the antioxidant activities of the peptides. For SET-based assay, tripeptide ECH displayed the highest DPPH radical scavenging activity (80.16%) and the strongest reducing power (A700=0.378). Besides, ECH also exhibited the best inhibition activity toward linoleic acid peroxidation with inhibition rate 98.25% at 7th day, which is a HAT-based assay. However, for another two HAT-based assays, it was tetrapeptide YECG that showed extraordinary oxygen radical absorption capacity (ORAC value=2.42μM Trolox/μM) and ABTS free radical scavenging ability (8.88mM Trolox/mM). In vitro cultured PC12 cell model also suggested that YECG gave the best protection for PC12 cells to resist H2O2-treated necrosis. It was found that the discrepancy of antioxidant capacity between ECH and YECG was caused by the presence of antioxidant amino acids (His/Tyr) and their position in peptide chain. With His located at C-terminal position, ECH demonstrated good electrons donating capacity, while with Tyr at N-terminal position, YECG exhibited strong oxygen radical absorbance capacity.