Redox metabolism is an important metabolic pathway in all apicomplexans. This pathway shows the series of oxidation/reduction activities involved in removal of oxidative radicals such as superoxide anions, hydrogen peroxide and other toxic nucleophiles produced from different metabolic reactions. These reactive oxygen species cause oxidative damage to DNA, lipids and proteins. There are several antioxidant systems present in cells to protect them from these damages. This includes enzymes such as superoxide dismutase which reduces superoxide anion to H2O2 and catalase which reduces H2O2 to water and oxygen. The enzyme peroxiredoxin also reduces H2O2. The oxidised peroxiredoxin can be reduced back by thiols such as glutathione and thioredoxin. The glutathione system consists of glutathione and the enzymes glutathione peroxidase, glutathione reductase and glutathione S-transferase. Glutathione is a tripeptide of glutamine-cysteine-glycine and synthesised de novo in two reactions steps. This glutathione synthesis is also included in this pathway. Glutathione peroxidase and glutathione S-transferase catalyse reduction of oxidative radicals by oxidising glutathione. Glutathione can be reduced back by glutathione reductase. Although glutathione synthase and glutathione S-transferase are present in Piroplasma species, glutathione peroxidase and glutathione reductase are absent in the gene models. Another redox protein thioredoxin is important in reduction of ribonucleotides to deoxyribonucleotides and its partner thioredoxin reductase catalyses reduction of oxidised thioredoxin using NADPH as electron donor. Catalase is also absent in Piroplasma species.
Redox metabolism Proteins
Peroxidases are a class of oxidoreductases produced by microorganisms or plants that can catalyze many reactions. Peroxidase is an enzyme that catalyzes the oxidation of a substrate by hydrogen peroxide as an electron acceptor. It is mainly present in the peroxisome of the carrier. It uses iron porphyrin as a prosthetic group. It can catalyze hydrogen peroxide, oxidize phenols and amines, and hydrocarbon oxidation products. It has the elimination of hydrogen peroxide and phenols and amines. The dual effects of toxicity of aldehydes, aldehydes and benzenes. Peroxidase is a type of oxidoreductase. It is distributed in milk, white blood cells, platelets and other body fluids or cells. The co-group of this enzyme is also heme. H2O2 is an electron acceptor that catalyzes the oxidation of substrates. It catalyzes H2O2 to directly oxidize phenols or amines, such as cereals. Glutathione peroxidase, eosinophil peroxidase, and thyroid peroxidase, etc., have the dual effect of eliminating the toxicity of hydrogen peroxide and phenolic amines. The reaction is as follows: R + H2O2RO + H2O or RH2 + In the clinical diagnosis of H2O2-R + 2H2O to observe the presence or absence of occult blood in stool, it is to use the activity of peroxidase in red blood cells to oxidize benzidine to a blue compound.
Figure 1. Protein structure of peroxidases.
Thioredoxin is a protein that acts as an antioxidant by promoting the reduction of other proteins through cysteine thiol-disulfide exchange. Thioredoxin is found in almost all known organisms and is vital to mammalian life. Various in vitro substrates of thioredoxin have been identified, including ribonuclease, chorionic gonadotropin, coagulation factors, glucocorticoid receptors, and insulin. Reduced insulin is often used as an activity test. The amino acid sequence level of thioredoxin is characterized by the presence of two ortho-cysteines in the CXXC motif. These two cysteines are key to the ability of thioredoxin to reduce other proteins. Thioredoxin also has a characteristic tertiary structure called thioredoxin folding. In a NADPH-dependent response, flavinase thioredoxin reductase keeps thioredoxin in a reduced state. Thioredoxin acts as an electron donor for peroxidase and ribonucleotide reductase.
Figure 2. Protein structure of thioredoxin.
Like thioredoxin, glutathione has an active central disulfide bond. It exists in reduced or oxidized form, where two cysteine residues are linked by intramolecular disulfide bonds. Glutathione toxin acts as an electron carrier in the glutathione-dependent deoxyribonucleotide synthesis of ribonucleotide reductase. In addition, GRX exerts antioxidant defense by reducing dehydroascorbic acid, redox protein, and methionine sulfoxide reductase. In addition to their role in antioxidant defense, bacterial and plant GRX have also been shown to bind iron-sulfur clusters and deliver clusters to enzymes as needed. Glutaraldehyde is oxidized by the substrate and non-enzymatically reduced by glutathione. In contrast to thioredoxin, which is reduced by thioredoxin reductase, there is no oxidoreductase that specifically reduces glutaraldehyde toxin. In contrast, glutathione is reduced by oxidation by glutathione. The oxidized glutathione is then regenerated by glutathione reductase. These components together make up the glutathione system.
Figure 3. Protein structure of glutathione.
1. Atamna H.; et al. Amyloid-beta peptide binds with heme to form a peroxidase: relationship to the cytopathologies of Alzheimer's disease. Proceedings of the National Academy of Sciences of the United States of America. 2006, 103 (9): 3381-6.