PRDX6 contributes to selenocysteine metabolism and ferroptosis resistance.

Selenocysteine (Sec) metabolism is crucial for cellular function and ferroptosis prevention and begins with the uptake of the Sec carrier, selenoprotein P (SELENOP). Following uptake, Sec released from SELENOP is metabolized via selenocysteine lyase (SCLY), producing selenide, a substrate for selenophosphate synthetase 2 (SEPHS2), which provides the essential selenium donor, selenophosphate (HSePO), for the biosynthesis of the Sec-tRNA. Here, we discovered an alternative pathway in Sec metabolism mediated by peroxiredoxin 6 (PRDX6), independent of SCLY.

PRDX6 contributes to selenocysteine metabolism and ferroptosis resistance.

Selenocysteine (Sec) metabolism is crucial for cellular function and ferroptosis prevention and has traditionally been thought to begin with the uptake of the Sec carrier selenoprotein P (SELENOP). Following uptake, Sec released from SELENOP undergoes metabolisation via selenocysteine lyase (SCLY), producing selenide, a substrate used by selenophosphate synthetase 2 (SEPHS2), which provides the essential selenium donor - selenophosphate - for the biosynthesis of the selenocysteine tRNA. Here, we report the discovery of an alternative pathway mediating Sec metabolisation that is independent of SCLY and mediated by peroxiredoxin 6 (PRDX6).

Maternal seafood consumption is associated with improved selenium status: Implications for child health.

Selenium (Se) is required for synthesis of selenocysteine (Sec), an amino acid expressed in the active sites of Se-dependent enzymes (selenoenzymes), including forms with essential functions in fetal development, brain activities, thyroid hormone metabolism, calcium regulation, and to prevent or reverse oxidative damage. Homeostatic mechanisms normally ensure the brain is preferentially supplied with Se to maintain selenoenzymes, but high methylmercury (CHHg) exposures irreversibly inhibit their activities and impair Sec synthesis. Due to Hg's high affinity for sulfur, CHHg initially binds with the cysteine (Cys) moieties of thiomolecules which are selenoenzyme substrates.

Prolonged maternal exposure to glucocorticoids alters selenoprotein expression in the developing brain.

Aberrant activation of the stress-response system in early life can alter neurodevelopment and cause long-term neurological changes. Activation of the hypothalamic-pituitary-adrenal axis releases glucocorticoids into the bloodstream, to help the organism adapt to the stressful stimulus. Elevated glucocorticoid levels can promote the accumulation of reactive oxygen species, and the brain is highly susceptible to oxidative stress.

Selenium Protects Mouse Hypothalamic Cells from Glucocorticoid-Induced Endoplasmic Reticulum Stress Vulnerability and Insulin Signaling Impairment.

The use of glucocorticoid medications is known to cause metabolic side effects such as overeating, excess weight gain, and insulin resistance. The hypothalamus, a central regulator of feeding behavior and energy expenditure, is highly responsive to glucocorticoids, and it has been proposed that it plays a role in glucocorticoid-induced metabolic defects. Glucocorticoids can alter the expression and activity of antioxidant enzymes and promote the accumulation of reactive oxygen species.

Metabolism of Selenium, Selenocysteine, and Selenoproteins in Ferroptosis in Solid Tumor Cancers.

A potential target of precision nutrition in cancer therapeutics is the micronutrient selenium (Se). Se is metabolized and incorporated as the amino acid selenocysteine (Sec) into 25 human selenoproteins, including glutathione peroxidases (GPXs) and thioredoxin reductases (TXNRDs), among others. Both the processes of Se and Sec metabolism for the production of selenoproteins and the action of selenoproteins are utilized by cancer cells from solid tumors as a protective mechanism against oxidative damage and to resist ferroptosis, an iron-dependent cell death mechanism.

Selenium and selenoproteins in thermogenic adipocytes.

Selenium (Se) is involved in energy metabolism in the liver, white adipose tissue, and skeletal muscle, and may also play a role in thermogenic adipocytes, i.e. brown and beige adipocytes.

Challenging Aspects to Precise Health Strategies in Native Hawaiian and Other Pacific Islanders Using Statins.

Cardiometabolic disorders (CD), including cardiovascular disease (CVD), diabetes, and obesity, are the leading cause of health concern in the United States (U.S.), disproportionately affecting indigenous populations such a Native Hawaiian and Other Pacific Islanders (NHOPI).

Selenotranscriptome Network in Non-alcoholic Fatty Liver Disease.

Observational studies indicate that selenium may contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Transcriptomic exploration of the aetiology and progression of NAFLD may offer insight into the role selenium plays in this disease. This study compared gene expression levels of known selenoprotein pathways between individuals with a healthy liver to those with NAFLD.

Female Mice with Selenocysteine tRNA Deletion in Agrp Neurons Maintain Leptin Sensitivity and Resist Weight Gain While on a High-Fat Diet.

The role of the essential trace element selenium in hypothalamic physiology has begun to come to light over recent years. Selenium is used to synthesize a family of proteins participating in redox reactions called selenoproteins, which contain a selenocysteine residue in place of a cysteine. Past studies have shown that disrupted selenoprotein expression in the hypothalamus can adversely impact energy homeostasis.

The Impact of Selenium Deficiency on Cardiovascular Function.

Selenium (Se) is an essential trace element that is necessary for various metabolic processes, including protection against oxidative stress, and proper cardiovascular function. The role of Se in cardiovascular health is generally agreed upon to be essential yet not much has been defined in terms of specific functions. Se deficiency was first associated with Keshan's Disease, an endemic disease characterized by cardiomyopathy and heart failure.

Regulation of thyroid hormones and branchial iodothyronine deiodinases during freshwater acclimation in tilapia.

Euryhaline fishes are capable of maintaining osmotic homeostasis in a wide range of environmental salinities. Several pleiotropic hormones, including prolactin, growth hormone, and thyroid hormones (THs) are mediators of salinity acclimation. It is unclear, however, the extent to which THs and the pituitary-thyroid axis promote the adaptive responses of key osmoregulatory organs to freshwater (FW) environments.

Intersection between Obesity, Dietary Selenium, and Statin Therapy in Brazil.

Obesity is among the most alarming health concerns, impacting public health and causing a socioeconomic challenge, especially in developing countries like Brazil, where approximately one quart of the population presents obesity. As an established risk factor for numerous comorbidities with a multifactorial etiology, obesity is a consequence of energy-dense overfeeding, however with significant undernourishment, leading to excessive adipose tissue accumulation and dysfunction, dyslipidemia, and micronutrient deficiencies. About 60% of patients with obesity take statins, a cholesterol-lowering medication, to curb dyslipidemia, with ~10% of these patients presenting various myopathies as side effects.

Effect of statin treatment in obese selenium-supplemented mice lacking selenocysteine lyase.

People with obesity are often dyslipidemic and prescribed statins to prevent cardiovascular events. A common side effect of statin use is myopathy. This could potentially be caused by the reduction of selenoproteins that curb oxidative stress, in turn, affecting creatine metabolism.

Adaptive Thermogenesis in a Mouse Model Lacking Selenoprotein Biosynthesis in Brown Adipocytes.

Selenoproteins are a class of proteins with the selenium-containing amino acid selenocysteine (Sec) in their primary structure. Sec is incorporated into selenoproteins via recoding of the stop codon UGA, with specific and factors required during translation to avoid UGA recognition as a stop codon, including a Sec-specific tRNA, tRNA, encoded in mice by the gene . Whole-body deletion of in mouse is embryonically lethal, while targeted deletion of in mice has been used to understand the role of selenoproteins in the health and physiology of various tissues.

Effects of selenium supplementation on diet-induced obesity in mice with a disruption of the selenocysteine lyase gene.

Background: The amino acid selenocysteine (Sec) is an integral part of selenoproteins, a class of proteins mostly involved in strong redox reactions. The enzyme Sec lyase (SCLY) decomposes Sec into selenide allowing for the recycling of the selenium (Se) atom via the selenoprotein synthesis machinery. We previously demonstrated that disruption of the Scly gene (Scly KO) in mice leads to the development of obesity and metabolic syndrome, with effects on glucose homeostasis, worsened by Se deficiency or a high-fat diet, and exacerbated in male mice.

Combined Omics Reveals That Disruption of the Selenocysteine Lyase Gene Affects Amino Acid Pathways in Mice.

Selenium is a nonmetal trace element that is critical for several redox reactions and utilized to produce the amino acid selenocysteine (Sec), which can be incorporated into selenoproteins. Selenocysteine lyase (SCL) is an enzyme which decomposes Sec into selenide and alanine, releasing the selenide to be further utilized to synthesize new selenoproteins. Disruption of the selenocysteine lyase gene () in mice ( or Scly KO) led to obesity with dyslipidemia, hyperinsulinemia, glucose intolerance and lipid accumulation in the hepatocytes.

Selenocysteine β-Lyase: Biochemistry, Regulation and Physiological Role of the Selenocysteine Decomposition Enzyme.

The enzyme selenocysteine β-lyase (SCLY) was first isolated in 1982 from pig livers, followed by its identification in bacteria. SCLY works as a homodimer, utilizing pyridoxal 5'-phosphate as a cofactor, and catalyzing the specific decomposition of the amino acid selenocysteine into alanine and selenide. The enzyme is thought to deliver its selenide as a substrate for selenophosphate synthetases, which will ultimately be reutilized in selenoprotein synthesis.

From Selenium Absorption to Selenoprotein Degradation.

Selenium is an essential dietary micronutrient. Ingested selenium is absorbed by the intestines and transported to the liver where it is mostly metabolized to selenocysteine (Sec). Sec is then incorporated into selenoproteins, including selenoprotein P (SELENOP), which is secreted into plasma and serves as a source of selenium to other tissues of the body.

SEXUAL DIMORPHISM IN SELENIUM METABOLISM AND SELENOPROTEINS.

Sexual dimorphism, the condition in which males and females in a species differ beyond the morphology of sex organs, delineates critical aspects of the biology of higher eukaryotes, including selenium metabolism. While sex differences in selenium biology have been described by several laboratories, delineation of the effects of sex in selenium function and regulation of selenoprotein expression is still in its infancy. This review encompasses the available information on sex-dependent parameters of selenium metabolism, as well as the effects of selenium on sex hormones.

Relationship between selenoprotein P and selenocysteine lyase: Insights into selenium metabolism.

Selenoprotein P (SelenoP) functions as a plasma transporter of selenium (Se) from liver to other tissues via incorporation into multiple selenocysteine (Sec) residues. Selenocysteine lyase (Scly) is an intracellular enzyme that decomposes Sec into selenide, providing Se for the synthesis of new selenoproteins. Both SelenoP and Scly are mostly produced by the liver.

Sexual Dimorphism in the Selenocysteine Lyase Knockout Mouse.

Selenium (Se) is an essential micronutrient known for its antioxidant properties and health benefits, attributed to its presence in selenoproteins as the amino acid, selenocysteine. Selenocysteine lyase (Scly) catalyzes hydrolysis of selenocysteine to selenide and alanine, facilitating re-utilization of Se for de novo selenoprotein synthesis. Previously, it was reported that male Scly mice develop increased body weight and body fat composition, and altered lipid and carbohydrate metabolism, compared to wild type mice.

Selenium and Metabolic Disorders: An Emphasis on Type 2 Diabetes Risk.

Selenium (Se) is a micronutrient that maintains biological functions through the action of Se containing proteins known as selenoproteins. Due to the known antioxidant effects of Se, supplements containing Se have been on the rise. While Se supplementation may be beneficial for Se deficient populations, few are at risk for Se deficiency due to the transportation of food from Se-rich regions and the rise of Se-enriched foods.