Background
Glutathione reductase (GR) is a crucial flavoenzyme in the antioxidant defense system. Reduced glutathione (GSH) is used by glutathione peroxidase to detoxify hydrogen peroxide and in the precess is converted to oxidized glutathione (GSSG). The GSSG is then recycled back to GSH by glutathione reductase (GR) using NADPH that is then converted to NADP+. The regenerated GSH is then available to detoxify more hydrogen peroxide. The enzyme uses FAD as a cofactor. GR and glutathione peroxidase may inhibit lipid peroxidation by functioning as antioxidant enzymes in sperm. Glutathione reductase shares a structural motif with a number of other proteins including aspartyl proteases, Citrate synthase, EF hands, hemoglobins, lipecalins, and α/β hydrolases. GR is stimulated by melatonin and is reportedly irreversibly inhibited by a number of oxygen radical generating systems.
Synonyms
EC 1.6.4.2; 9001-48-3; Glutathione Reductase; GR; glutathione reductase; glutathione reductase (NADPH); NADPH-glutathione reductase; GSH reductase; GSSG reductase; NADPH-GSSG reductase; glutathione S-reductase; NADPH:oxidized-glutathione oxidoreductase
Glutathione reductase (glutathione reductase) is an enzyme that uses reduced NAD (P) to catalyze the reaction of oxidized glutathione (GS-SG) into reduced form (GSH). Glutathione reductase (gluathione reductase) is one of the most important enzymes in the redox system of the human body, and is the main flavozyme that maintains the content of reduced glutathione (GSH) in cells. With the participation of NADPH, oxidized glutathione is converted into reduced glutathione, which plays an important role in preventing the oxidative decomposition of hemoglobin, maintaining the activity of sulfhydryl protein, ensuring the reducibility of sulfhydryl protein and cell integrity.
Figure 1. Protein structure of GR.
Clinical diagnosis significance
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Physiological increase of GR
Strong exercise: strenuous exercise can significantly increase GR and slower recovery during exercise. ALT activity is still increased by 30%-50% after 1 hour of stopping exercise. Therefore, avoid strenuous exercise before measuring GR to avoid the increase of GR due to activities, which will affect the correct interpretation of the measurement results.
Meals: The effects of meals on GR are due to individual differences between individuals. For a small number of individuals, meals can slightly increase GR activity.
Drinking: When alcohol is ingested into the human body, it varies from individual to individual. A certain amount of alcohol intake will increase GR activity.
Newborns: GR levels will increase, 1 to 3 times higher than normal adults, mainly due to jaundice, which can drop to normal adult levels 3-6 months after birth
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Pathologically increased GR
Liver diseases: acute hepatitis, drug-induced liver damage, toxic hepatitis, chronic hepatitis, liver cancer, early liver cirrhosis, etc. have obvious concomitant increases. Among patients with acute infectious hepatitis, serum GR activity was significantly increased. In the early stage of liver cirrhosis, GR will increase to varying degrees due to individual differences. However, in the late stage of cirrhosis, GR is often normal. In primary hepatocellular carcinoma and extensive metastatic liver tumors, serum GR increases significantly.
Functions
GSH is an antioxidant that protects -SH in protein molecules from oxidation and protects the activity of sulfhydryl proteins and enzymes. Under the action of glutathione peroxidase, GSH can reduce the H2O2 produced in the cell to produce H2O. At the same time, GSH is oxidized to oxidized glutathione (GSSG), which is in glutathione reductase. Under the catalysis, GSH is formed again. Therefore, glutathione reductase can reduce oxidized glutathione (GSSG) to produce reduced glutathione (GSH), which is one of the key enzymes in the glutathione redox cycle (usually GR in insects is Replaced by TrxR). Glutathione reductase catalyzes NADPH to reduce GSSG to produce GSH, which helps to maintain the ratio of GSH/GSSG in the body. Glutathione reductase plays a key role in the removal of reactive oxygen species in the oxidative stress reaction. In addition, GR also participates in the ascorbic acid-glutathione cycle pathway. Glutathione reductase is distributed in many tissues and can maintain sufficient levels of reduced glutathione (GSH) in cells. The absence of glutathione reductase makes cells more sensitive to oxidants and antibiotics.
Common measurement principles:
Glutathione reductase can catalyze the reduction of GSSG by NADPH to regenerate GSH, and at the same time NADPH dehydrogenation to generate NADP+; NADPH has a characteristic absorption peak at 340 nm, on the contrary, NADP+ has no absorption peak at this wavelength; NADPH desorption is determined by measuring the rate of decrease in absorbance at 340 nm. Hydrogen rate to calculate glutathione reductase activity.
Clinical significance
For patients with liver damage, the detection of glutathione reductase can help us understand whether the body's glutathione antioxidant system is functional. The decrease of glutathione reductase indicates that liver cells have decreased detoxification and antioxidant capacity. Supplementing exogenous GSH will help recovery. Normal or elevated glutathione reductase indicates normal liver detoxification function, without the need to supplement exogenous GSH. In addition, GSH can protect the sulfhydryl groups in certain proteins, such as protecting the sulfhydryl groups on the red blood cell membrane from oxide damage, protecting the integrity of the red blood cell membrane, and maintaining the normal structure and function of red blood cells. Therefore, the lack of GSH by red blood cells is very important. sensitive. Often in liver function tests, an increase in indirect bilirubin is associated with a decrease or depletion of GSH.