Selenium and Selenocysteine

///Selenium and Selenocysteine

Selenium and Selenocysteine

Selenium and Selenocysteine: the functional selenium for antioxidant benefits and combatting commercial stresses

 

 

Peter SURAI1 & Pierre-Andre GERAERT2

1FeedFood Ltd, 2Adisseo France SAS

 

In breeder and broiler industries, the environment and external parameters can induce stress factors, which may result in a lower production and reproduction for birds. Stressful conditions cause consequences on the metabolism, and especially in the hypothalamic-pituitary-adrenal axis, the autonomic nervous system and the immune system are in charge of setting up back homeostasis. In order to re-establish the correct balance, many regulatory reactions are triggered, using energy and provoking a change in the metabolism, lowering growth performance and feed efficiency. In the poultry industry, four main types of stress are accounted: technological, environmental, nutritional and internal. Research works demonstrated that most cellular-level stressors for poultry production are linked with an excessive reactive oxygen species (ROS) or an inappropriate antioxidant protection. This is supported by a large feed intake to reach a rapid growth of the broilers leading as well to an enhanced oxidative metabolism and the formation of free radicals.

 

In order to fight against ROS and reactive nitrogen species (RNS), scientific communities agreed that living organisms developed specific antioxidant protective mechanisms. Moreover, it is thanks to these natural systems that living organisms can survive in oxygen rich environment, usually named “antioxidant system”. It is varied and in charge of protecting the cells from the actions of free radicals.

 

Table 1: Categories included in the antioxidant system

CategoryExampleS
Natural fat-soluble antioxidantsVitamins A, E, carotenoids, ubiquinones
Water-soluble antioxidantsAscorbic acid, uric acid, taurine, carnitine
Antioxidants enzymesGlutathione peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD)
Thiol redox systems consisting of a glutathione systemGlutathione, glutathione reductase, glutathione peroxidase
Thiol redox systems consisting of a thioredoxin systemThioredoxin peroxidase, thioredoxin reductase

 

Generally, in both intra and extracellular antioxidant systems, all the components have a specific function and work together in order to create an efficient defense system. Selenium is one of the main player in the antioxidant defense. Recently, this concept has been updated, especially on cell signaling. In animal kingdom, including poultry, RIS are used in redox signaling pathways to transfer signals from different sources to the nucleus to regular various functions, like growth, differentiation, proliferation or apoptosis for instance.

 

Selenium: molecular mechanisms in poultry nutrition

Selenium is the main component of selenoproteins and plays an active role to determine their biological functions. For chicken, 25 SeCys-based proteins have been identified. They have diverse distribution, subcellular localization and function. For instance, the following compounds can be cited to:

  • Detoxify oxidants: glutathione peroxidase (GSH-Px)-1, -2, -3, -4, TrxR-1, -2 and -3, selenoprotein P;
  • Reduce free and protein-bound oxidized Met: selenoprotein R/MsrB1;
  • Ensure redox homeostasis: selenoproteins K, M, N and H.

 

Knowledge of chicken selenoproteins is still limited, despite the identification of half of them as being oxidoreductases. It is known that they are involved in glutathione-dependent hydroperoxide removal, reduction of thioredoxins, selenophosphate synthesis, activation and inactivation of thyroid hormones, thioredoxin-dependent repair of oxidized methionine residues and endoplasmic reticulum associated protein degradation. It explains more the role of selenium in animal health and reinforces its importance in antioxidant defense, immune system regulation and other functions. High tissue specificity is one characteristic of the expression of individual eukaryotic selenoproteins, but the Se availability, which is hormones dependent is another one which can be referenced. If the expression is compromised, it enhances various pathological conditions (Surai, 2006).

 

 

Selenocysteine: the functional selenium

 

Selenium roles can be explained in the major part through specific SeCys-containing proteins, as well in humans. Due to its late identification, SeCys is considered to be the 21st amino acid and deciphering selenoprotein synthesis mechanisms definitely helped with the understanding of the genetic code. In the middle 1960s, only 20 amino acids were taken into account in the code for the newly synthetized proteins. It created 64 possible codons in which 3 were identified as being terminators for protein synthesis. However, scientists discovered that UGA was not only dedicated for a terminal codon, but serves as well a SeCys codon. When SeCys is incorporated into protein, this dual role codon moves from translation termination to a specific one to SeCys. It makes the identification of novel selenoproteins genes more difficult.

If SeCys is located in the catalytic site of selenium-dependent antioxidant enzymes, it promotes the kinetic properties and enhances the catalytic activity of antioxidant enzymes against biological oxidants when compared with sulfur-containing species. This rare amino acid plays a critical role can be illustrated by mutagenesis studies of mammalian and bacterial selenoproteins. For every experiment, there was a significant decrease of the catalytic activity if the native active-site selenocysteine was replaced by a cysteine residue.

SeCys represents a unique proteinogenic amino acid in the way it includes an essential trace element, selenium, and requires complex tRNA-dependent synthetic machinery for its synthesis, delivery to the ribosome and insertion into the nascent selenoprotein. Indeed, cysteine and SeCys are involved in many redox pathways, unlike any other amino acid, including exchange and radical reactions as well as atom, electron-, and hybrid-transfer reactions. Additionally, selenium is classified in the periodic table between the metals and non-metals, which confer selenoproteins effective catalyst properties for many biological redox transformations (Jacob et al., 2003). Selenoproteins expression in various chicken tissues mostly depends on selenium availability and stress.

 

OH-SeMethionine: a source of functional selenium as SeCys

 

Historically, selenium supplementation was made through mineral sources. However, to cover selenium requirements with a minimum addition for enzyme synthesis, selenate or selenite are not efficient enough to enable Se deposition in the tissues compared to SeMet. In return, organic sources of selenium have shown positive results in SeMet deposition and this for different tissues. This way, when the organism is undergoing oxidative stress, SeMet reserve can be used. The reserve form of selenium in the tissues can only be as SeMet, non-specifically deposited within proteins, unlike methionine, or as SeCys, part of the selenoproteins. Levels of SeMet and SeCys can thereafter be measured in every tissue. For example in dairies, whereas milk is rich in SeMet, blood contains more SeCys. In chickens and swine, SeMet is in a higher amount in deposition tissues, like muscles, while SeCys is mainly found in metabolic tissues, like the liver, kidneys and pancreas.

 

L-SeMet and OH-SeMet, which are pure sources of organic Se, have shown better results than selenised yeasts or other so-called organic forms of Se in terms of increasing SeMet deposition in the tissues (figure 1).

Figure 1: Se Muscle deposition in 7Day-chickens, fed with various sources of selenium expressed relative to SO: SO (OH-SeMet), SM (L-SeMet), ZnSM (Zn chelate of SeMet), SYH (SeYeast containing 72% SeMet), SYL (SeYeast containing 32% SeMet), HLAN (SeYeast containing mainly Se-HomoLanthionine), SeP (Se proteinate), SeG (Se glycinate), NaS (sodium selenite)

For low doses of supplementation (0.2-0.3ppm of Se), SeMet and OH-SeMet show equivalent results in terms of Se deposition. However, in order to build SeCys from Se already involved in SeMet is not tissue or protein specific during oxidative stress and antioxidant demand. This is why creating enough reserves through selenoproteins in the metabolic tissues is crucial to help the organism fight against oxidative stress. OH-SeMet enhances more SeCys synthesis than SeMet, and thus helps the enrichment of tissues in selenoproteins, which is the functional form of Se for antioxidant purposes (figure 2). It comes with surprise the higher SeCys:SeMet ratios in various tissues in broilers, layers, swine and even dairies.

 

Figure 2: SeCys content (%) measured in various species (chickens, layers and dairies) and in different tissues (blood, muscle, egg); *: P<0.05; Broiler muscle: breast

 

 

Perspectives

 

Research to improve genetics has changed drastically the farm animals into optimized species able to eat a large amount of feed, with a strong metabolic rate and protein deposition. In the same time, this progress has increased the exposure to free radicals, ROS and NOS, because the tremendous metabolic rate involves a need for antioxidant protection and allows them to express in a complete way their genetic potential. Additionally, under specific conditions like in southern hemisphere and hot countries, the exposure to more challenged feeds due to diverse raw materials or mycotoxins reinforces the need for antioxidant protection. Selenium is a major actor in the antioxidant balance. Indeed, it is located in the catalytic sites of selenoproteins involved in redox homeostasis through SeCys. This way, it is essential to supplement feed with readily available sources of functional selenium. OH-SeMet seems to be the adequate solution to provide SeCys.

Selenium and Selenocysteine: the functional selenium for antioxidant benefits and combatting commercial stresses

 

Peter SURAI1 & Pierre-Andre GERAERT2
1FeedFood Ltd, 2Adisseo France SAS

 

In breeder and broiler industries, the environment and external parameters can induce stress factors, which may result in a lower production and reproduction for birds. Stressful conditions cause consequences on the metabolism, and especially in the hypothalamic-pituitary-adrenal axis, the autonomic nervous system and the immune system are in charge of setting up back homeostasis. In order to re-establish the correct balance, many regulatory reactions are triggered, using energy and provoking a change in the metabolism, lowering growth performance and feed efficiency. In the poultry industry, four main types of stress are accounted: technological, environmental, nutritional and internal. Research works demonstrated that most cellular-level stressors for poultry production are linked with an excessive reactive oxygen species (ROS) or an inappropriate antioxidant protection. This is supported by a large feed intake to reach a rapid growth of the broilers leading as well to an enhanced oxidative metabolism and the formation of free radicals.

In order to fight against ROS and reactive nitrogen species (RNS), scientific communities agreed that living organisms developed specific antioxidant protective mechanisms. Moreover, it is thanks to these natural systems that living organisms can survive in oxygen rich environment, usually named “antioxidant system”. It is varied and in charge of protecting the cells from the actions of free radicals.

Table 1: Categories included in the antioxidant system
CATEGORY EXAMPLES
Natural fat-soluble antioxidants Vitamins A, E, carotenoids, ubiquinones
Water-soluble antioxidants Ascorbic acid, uric acid, taurine, carnitine
Antioxidants enzymes Glutathione peroxidase (GSH-Px), catalase (CAT), superoxide dismutase (SOD)
Thiol redox systems consisting of a glutathione system Glutathione, glutathione reductase, glutathione peroxidase
Thiol redox systems consisting of a thioredoxin system Thioredoxin peroxidase, thioredoxin reductase

Generally, in both intra and extracellular antioxidant systems, all the components have a specific function and work together in order to create an efficient defense system. Selenium is one of the main player in the antioxidant defense. Recently, this concept has been updated, especially on cell signaling. In animal kingdom, including poultry, RIS are used in redox signaling pathways to transfer signals from different sources to the nucleus to regular various functions, like growth, differentiation, proliferation or apoptosis for instance.

Selenium: molecular mechanisms in poultry nutrition
Selenium is the main component of selenoproteins and plays an active role to determine their biological functions. For chicken, 25 SeCys-based proteins have been identified. They have diverse distribution, subcellular localization and function. For instance, the following compounds can be cited to:
• Detoxify oxidants: glutathione peroxidase (GSH-Px)-1, -2, -3, -4, TrxR-1, -2 and -3, selenoprotein P;
• Reduce free and protein-bound oxidized Met: selenoprotein R/MsrB1;
• Ensure redox homeostasis: selenoproteins K, M, N and H.

Knowledge of chicken selenoproteins is still limited, despite the identification of half of them as being oxidoreductases. It is known that they are involved in glutathione-dependent hydroperoxide removal, reduction of thioredoxins, selenophosphate synthesis, activation and inactivation of thyroid hormones, thioredoxin-dependent repair of oxidized methionine residues and endoplasmic reticulum associated protein degradation. It explains more the role of selenium in animal health and reinforces its importance in antioxidant defense, immune system regulation and other functions. High tissue specificity is one characteristic of the expression of individual eukaryotic selenoproteins, but the Se availability, which is hormones dependent is another one which can be referenced. If the expression is compromised, it enhances various pathological conditions (Surai, 2006).

Table 2: Selenoprotein functions in avian species

Selenocysteine: the functional selenium

Selenium roles can be explained in the major part through specific SeCys-containing proteins, as well in humans. Due to its late identification, SeCys is considered to be the 21st amino acid and deciphering selenoprotein synthesis mechanisms definitely helped with the understanding of the genetic code. In the middle 1960s, only 20 amino acids were taken into account in the code for the newly synthetized proteins. It created 64 possible codons in which 3 were identified as being terminators for protein synthesis. However, scientists discovered that UGA was not only dedicated for a terminal codon, but serves as well a SeCys codon. When SeCys is incorporated into protein, this dual role codon moves from translation termination to a specific one to SeCys. It makes the identification of novel selenoproteins genes more difficult.
If SeCys is located in the catalytic site of selenium-dependent antioxidant enzymes, it promotes the kinetic properties and enhances the catalytic activity of antioxidant enzymes against biological oxidants when compared with sulfur-containing species. This rare amino acid plays a critical role can be illustrated by mutagenesis studies of mammalian and bacterial selenoproteins. For every experiment, there was a significant decrease of the catalytic activity if the native active-site selenocysteine was replaced by a cysteine residue.
SeCys represents a unique proteinogenic amino acid in the way it includes an essential trace element, selenium, and requires complex tRNA-dependent synthetic machinery for its synthesis, delivery to the ribosome and insertion into the nascent selenoprotein. Indeed, cysteine and SeCys are involved in many redox pathways, unlike any other amino acid, including exchange and radical reactions as well as atom, electron-, and hybrid-transfer reactions. Additionally, selenium is classified in the periodic table between the metals and non-metals, which confer selenoproteins effective catalyst properties for many biological redox transformations (Jacob et al., 2003). Selenoproteins expression in various chicken tissues mostly depends on selenium availability and stress.

OH-SeMethionine: a source of functional selenium as SeCys

Historically, selenium supplementation was made through mineral sources. However, to cover selenium requirements with a minimum addition for enzyme synthesis, selenate or selenite are not efficient enough to enable Se deposition in the tissues compared to SeMet. In return, organic sources of selenium have shown positive results in SeMet deposition and this for different tissues. This way, when the organism is undergoing oxidative stress, SeMet reserve can be used. The reserve form of selenium in the tissues can only be as SeMet, non-specifically deposited within proteins, unlike methionine, or as SeCys, part of the selenoproteins. Levels of SeMet and SeCys can thereafter be measured in every tissue. For example in dairies, whereas milk is rich in SeMet, blood contains more SeCys. In chickens and swine, SeMet is in a higher amount in deposition tissues, like muscles, while SeCys is mainly found in metabolic tissues, like the liver, kidneys and pancreas.

L-SeMet and OH-SeMet, which are pure sources of organic Se, have shown better results than selenised yeasts or other so-called organic forms of Se in terms of increasing SeMet deposition in the tissues (figure 1).

Figure 1: Se Muscle deposition in 7Day-chickens, fed with various sources of selenium expressed relative to SO: SO (OH-SeMet), SM (L-SeMet), ZnSM (Zn chelate of SeMet), SYH (SeYeast containing 72% SeMet), SYL (SeYeast containing 32% SeMet), HLAN (SeYeast containing mainly Se-HomoLanthionine), SeP (Se proteinate), SeG (Se glycinate), NaS (sodium selenite)
For low doses of supplementation (0.2-0.3ppm of Se), SeMet and OH-SeMet show equivalent results in terms of Se deposition. However, in order to build SeCys from Se already involved in SeMet is not tissue or protein specific during oxidative stress and antioxidant demand. This is why creating enough reserves through selenoproteins in the metabolic tissues is crucial to help the organism fight against oxidative stress. OH-SeMet enhances more SeCys synthesis than SeMet, and thus helps the enrichment of tissues in selenoproteins, which is the functional form of Se for antioxidant purposes (figure 2). It comes with surprise the higher SeCys:SeMet ratios in various tissues in broilers, layers, swine and even dairies.

Figure 2: SeCys content (%) measured in various species (chickens, layers and dairies) and in different tissues (blood, muscle, egg); *: P<0.05; Broiler muscle: breast

 

Perspectives

Research to improve genetics has changed drastically the farm animals into optimized species able to eat a large amount of feed, with a strong metabolic rate and protein deposition. In the same time, this progress has increased the exposure to free radicals, ROS and NOS, because the tremendous metabolic rate involves a need for antioxidant protection and allows them to express in a complete way their genetic potential. Additionally, under specific conditions like in southern hemisphere and hot countries, the exposure to more challenged feeds due to diverse raw materials or mycotoxins reinforces the need for antioxidant protection. Selenium is a major actor in the antioxidant balance. Indeed, it is located in the catalytic sites of selenoproteins involved in redox homeostasis through SeCys. This way, it is essential to supplement feed with readily available sources of functional selenium. OH-SeMet seems to be the adequate solution to provide SeCys.

2017-06-26T14:05:19+00:00