The superoxide dismutases (SOD) or superoxide oxidoreductases, are a family of enzymes ubiquitous in nature, whose function is main defending the aerobic organisms against oxygen free radicals, especially superoxide anionic radicals.
The reaction that these enzymes catalyze occurs in virtually all cells that are capable of breathing (aerobic) and is essential for their survival, as it removes toxic free radicals from oxygen, both in eukaryotes and prokaryotes.
Graphic representation of a Cu-Zn Superoxide Dismutase (SOD) (Source: Jawahar Swaminathan and MSD staff at the European Bioinformatics Institute via Wikimedia Commons)
Many diseases in animals are related to the accumulation of different reactive oxygen species, and the same is true for plants, since the environment imposes numerous and constant types of oxidative stress that are overcome thanks to the activity of superoxide dismutases.
This group of enzymes was discovered in 1969 by McCord and Fridovich and since then considerable advances have been made regarding these enzymes and the reactions they catalyze in living things.
characteristics
Superoxide dismutases react with superoxide radicals at very high rates, which translates into a very effective line of defense for the removal of these molecules.
In mammals, at least three isoforms have been described for superoxide dismutase known as SOD1, SOD2, and SOD3, respectively.
Two of these isoforms have copper and zinc atoms in their catalytic centers and differ from each other in their location: intracellular (cytosolic, SOD1 or Cu / Zn-SOD) or with extracellular elements (EC-SOD or SOD3).
The SOD2 or Mn-SOD isoform, unlike the previous two, has a manganese atom as a cofactor and its location seems to be restricted to the mitochondria of aerobic cells.
SOD1 isoenzymes are found mainly in the cytosol, although they have also been detected in the nuclear compartment and in lysosomes. SOD 3 isoenzymes, on the other hand, have been described in human blood plasma, lymph, and cerebrospinal fluids.
Each of these isoforms is encoded by different genes, but belonging to the same family and their transcriptional regulation is essentially controlled by extra- and intracellular conditions, which trigger different internal signaling cascades.
Other superoxide dismutases
Superoxide dismutases with catalytic sites that possess copper and zinc or manganese ions are not unique to mammals, they are also present in other organisms including plants and bacteria of different classes.
There is an additional group of superoxide dismutases, which are not found in mammals, and which are easily recognizable, since in their active site they contain iron instead of any of the three ions previously described for the other classes of superoxide dismutases.
In E. coli, the iron-containing superoxide dismutase is a periplasmic enzyme that is also responsible for the detection and elimination of oxygen free radicals generated during respiration. This enzyme is similar to that found in the mitochondria of many eukaryotes.
Plants have the three types of enzymes: those that contain copper and zinc (Cu / Zn-SOD), those that contain manganese (Mn-SOD) and those that contain iron (Fe-SOD) in their active center and in these organisms. they exert analogous functions to those of non-vegetable enzymes.
Reaction
The substrates of superoxide dismutases are superoxide anions, which are represented as O2- and which are intermediates in the oxygen reduction process.
The reaction they catalyze can be broadly viewed as the transformation (dismutation) of free radicals to form molecular oxygen and hydrogen peroxide, which are released into the medium or used as a substrate for other enzymes, respectively.
Hydrogen peroxide can be subsequently eliminated from cells thanks to the action of any of the enzymes glutathione peroxidase and catalase, which also have important functions in cell protection.
Structure
The superoxide dismutases isoenzymes in humans may differ from each other in certain structural aspects. For example, the SOD1 isoenzyme has 32 kDa molecular weight, while SOD2 and SOD3 are homotetramers of 95 and 135 kDa molecular weight, respectively.
The other group of superoxide dismutases, the Fe-SODs present in plants and organisms other than mammals, are dimeric enzymes with identical subunits, that is, they are homodimers.
In some plants, these Fe-SOD contain a putative N-terminal signal sequence for transport into chloroplasts and others contain a C-terminal tripeptide sequence for transport to peroxisomes, so its subcellular distribution is presumed to be restricted to both compartments.
The molecular structure of the three types of superoxide dismutase enzymes is essentially made up of alpha helices and B-folded sheets.
Features
Superoxide dismutases defend cells, organs, and body tissues from the damage that oxygen free radicals can cause such as lipid peroxidation, protein denaturation, and DNA mutagenesis.
In animals, these reactive species can also cause heart damage, accelerate aging, and participate in the development of inflammatory diseases.
Plants also require the essential enzymatic activity of superoxide dismutase, since many stressful conditions in the environment increase oxidative stress, that is, the concentration of deleterious reactive species.
In humans and other mammals, the three isoforms described for superoxide dismutase have different functions. The SOD2 isoenzyme, for example, participates in cell differentiation and tumorigenesis and also in protection against hyperoxia (elevated oxygen concentration) -induced pulmonary toxicity.
For some species of pathogenic bacteria, SOD enzymes function as "virulence factors" that allow them to overcome many oxidative stress barriers that they may face during the invasion process.
Related diseases
A decrease in superoxide dismutase activity can occur due to several factors, both internal and external. Some are related to direct genetic defects in the genes encoding SOD enzymes, while others may be indirect, related to the expression of regulatory molecules.
A large number of pathological conditions in humans are related to SOD enzymes, including obesity, diabetes, cancer, and others.
With respect to cancer, it has been determined that there are a large number of cancerous tumor types that possess low levels of any of the three mammalian superoxide dismutases (SOD1, SOD2, and SOD3).
The oxidative stress that superoxide dismutase activity prevents, is also associated with other joint pathologies such as osteoarthritis, rheumatoid arthritis. Many of these diseases are related to the expression of factors that inhibit SOD activity, such as factor TNF-α.
References
- Fridovich, I. (1973). Superoxide Dismutases. Annu. Rev. Biochem., 44, 147-159.
- Johnson, F., & Giulivi, C. (2005). Superoxide dismutases and their impact upon human health. Molecular Aspects of Medicine, 26, 340–352.
- Oberley, LW, & Bueftner, GR (1979). Role of Superoxide Dismutase in Cancer: A Review. Cancer Research, 39, 1141-1149.
- Taylor, P., Bowler, C., Camp, W. Van, Montagu, M. Van, Inzé, D., & Asada, K. (2012). Superoxide Dismutase in Plants. Critical Reviews in Plant Sciences, 13 (3), 37–41.
- Zelko, I., Mariani, T., & Folz, R. (2002). Superoxide dismutase Multigene Family: A comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) Gene Structures, Evolution, and Expression. Free Radical Biology & Medicine, 33 (3), 337–349.