Selenium performs its functions as an integral component of proteins and enzymes, respectively. Relevant enzymes include selenium-containing glutathione peroxidases (GPxs), deiodases – types 1, 2, and 3 -, thioredoxin reductases (TrxR), selenoprotein P as well as W, and selenophosphate synthetase.Selenium deficiency leads to loss of activity of these proteins.
Selenium-dependent enzymes
Glutathione peroxidases The four known glutathione peroxidases include cytosolic GPx, gastrointestinal GPx, plasma GPx, and phospholipid hydroperoxide GPx. Although each of these selenium-containing enzymes has its specific functions, they share the common task of eliminating oxygen radicals, particularly in the aqueous environment of the cytosol and the mitochondrial matrix, respectively, thus contributing to protection against oxidative damage. For this purpose, selenium-rich proteins reduce organic peroxides such as hydrogen peroxide and lipid hydroperoxide to water. Hydrogen peroxide (H2O2) can form in nature wherever atomic oxygen acts on water. It is formed during the oxidation of inorganic and organic substances in air, as well as during many biological oxidation processes, such as respiration or fermentation. If peroxides are not broken down, they can lead to cell and tissue damage. The selenium-containing glutathione peroxidases are mainly found in the erythrocytes (red blood cells), the thrombocytes (blood platelets), the phagocytes (scavenger cells) such as in the liver and in the eyes. These reach their maximum activity at a selenium intake of 60-80 µg/day. Furthermore, selenium is present in high concentrations in the thyroid gland. Sufficient selenium intake is essential for normal thyroid function. As a component of glutathione peroxidases, selenium protects the endocrine organ from hydrogen peroxide attack during thyroid hormone synthesis. Glutathione peroxidases work closely with vitamin E in eliminating oxygen radicals. Vitamin E is a fat-soluble vitamin and therefore exerts its antioxidant effect in the membrane structure. Selenium and vitamin E can substitute each other in their effect. If the supply of vitamin E is good, it can scavenge oxygen radicals formed in the cytosol when selenium is deficient and protect the membrane from oxidative damage. Conversely, if selenium supply is sufficient, selenium-containing glutathione peroxidase is able to compensate for a deficiency of vitamin E by also removing peroxides in the cytoplasm, thereby protecting membranes from lipid peroxidation. Deiodases As a component of type 1 iodothyronine 5′-deiodase, which is found primarily in liver, kidney, and muscle, selenium is important in the activation and deactivation of thyroid hormones. Deiodase catalyzes the conversion of the prohormone thyroxine (T4) to the biologically active thyroid hormone 3,3′ 5-triiodothyronine (T3), as well as the conversion of T3 and reverse T3 (rT3) to inactive 3,3’diiodothyronine (T2). If selenium intake is insufficient, there is an increase in the serum T4 to T3 ratio, which may be associated with thyroid dysfunction. Similarly, selenium intake in excess of requirements leads to changes in thyroid hormone metabolism. By regulating the supply of T4 and T3 from the mother to the fetus during pregnancy, selenium-dependent type 3 deiodases protect the fetuses from excessive amounts of T3. Type 3 deiodases also influence local concentrations of T3 in other organs, especially in the brain. Selenoprotein P and W The function of selenoprotein P is not yet fully understood. It is suspected that it is important as an extracellular antioxidant – degradation of peroxinitrite – and protects biomembranes from lipid peroxidation. In addition, selenoprotein P may be responsible for mobilizing selenium from the liver to other organs such as the brain and kidney. The involvement of the protein in heavy metal binding is also discussed. Selenoprotein W is predominantly found in muscle tissue, but is also present in the brain and other tissues. Little is known about its function. However, it has been demonstrated that muscular dystrophies in humans can be positively influenced by selenium administration. Thioredoxin reductases The selenium-containing thioredoxin reductase family, which includes TrxR1, TrxR3 and TGR, plays an essential role in the reduction of oxidized thioredoxin and other substances such as dehydroascorbic acid and lipid hydroperoxides.The thioredoxin-thioredoxin reductase system regulates redox-sensitive transcription factors and protein folding via a reduction of disulfide bridges. In addition, selenium is involved in DNA biosynthesis, cell growth and apoptosis (programmed cell death) of tumor cells via thioredoxin reductases. In addition, the selenium-containing enzyme is important for the regeneration of antioxidant vitamin E. Selenophosphate synthetase Selenophosphate synthetase depends on sufficient selenium supply to control the first step of biosynthesis of other selenoproteins.
Other selenoproteins
In addition to the proteins mentioned above, there are other enzymes that require selenium for optimal activity. One example is the selenoprotein with a molecular weight of 34 kDa. This is found primarily in the gonads and in the prostate epithelium. Accordingly, selenium is essential for spermatogenesis and reproduction (reproduction). According to studies, male mammals in particular become infertile (infertile) when deficient in selenium. Furthermore, selenoproteins are present in the female ovaries, adrenal glands and pancreas. Quite a few selenoproteins are currently still being investigated with regard to their function and may also be important in tumorigenesis (cancer development).
Immune function
Selenium is said to have numerous immunomodulatory effects as a stimulator of humoral and cellular immunity:
- Production of antibodies, particularly IgG, gamma interferon, and tumor necrosis factor (TNF).
- Stimulation of neutrophil chemotaxis.
- Inhibition of suppressor cell activity
- Increasing the cytotoxicity of natural killer (NK) cells and cytotoxic T lymphocytes.
These effects of selenium depend on the level of selenium intake. Both a deficiency of selenium, as a result of inadequate intake, and an overdose of the trace element can lead to an impairment of the immune system. For example, selenium deficiencies negatively affect the activity of glutathione peroxidases, resulting in increased radical formation and increased accumulation of lipid hydroperoxides. This, in turn, is associated with increased formation of pro-inflammatory prostaglandins.
Heavy metal binding
Selenium is able to protect the body from harmful heavy metals such as lead, cadmium and mercury. The trace element forms a poorly soluble biologically inactive selenide-protein complex with the heavy metals, rendering them harmless. Finally, the absorption of lead, cadmium and mercury is significantly reduced. Excessive exposure to heavy metals can significantly increase the need for selenium, as the trace element must be constantly provided for heavy metal binding.
