Selenoprotein P (SELENOP) und Selenoprotein-P-Autoantikörper: the pathway in the body

Selenoprotein P (SELENOP) und Selenoprotein-P-Autoantikörper is part of the pathway “Selenium”. This page shows the whole pathway; the station of Selenoprotein P (SELENOP) und Selenoprotein-P-Autoantikörper is highlighted.

Where this laboratory value sits: Selenoprotein P — selenium in the blood. When reading the genetic code, the cell inserts selenocysteine at the UGA codon; a signal in the RNA (SECIS element) makes this possible. The liver releases selenoprotein P into the blood; it carries selenium to the tissues. It falls early with low supply. Source 3, 1

In brief

Selenium is a trace element that the body incorporates into proteins as selenocysteine. These selenoproteins convert peroxides to water and switch thyroid hormones into their active or inactive form. When little selenium arrives, the body distributes it by rank.

The pathway step by step

Each station states what the compound does there. Three signs: ↑ supplies — builds up or makes available · ↓ depletes — inhibits, consumes or withholds · ↕ both, depending on amount. Behind it stands what the statement rests on: established physiology, observed in studies, or contested. The signs do not grade; they name the direction.

1. Selenium in food → Selenide Selenocysteine lyase · Vitamin B6 (PLP) Selenocysteine lyase releases the selenium from the amino acid. Selenide is the common hub that feeds all further steps. From here one path leads into selenoproteins, another to excretion. Source 1, 2↕ both, depending on amount Selenide is the junction: from here selenium goes either into selenoproteins or into methylation for excretion. Free selenide is highly reactive and is therefore processed quickly. established physiology Source 2, 1
   ⚖ When the balance tips

   too much — If selenide builds up, it reacts with sulphur groups and oxygen; in cell culture this produces reactive oxygen species. This is the process by which very large amounts of selenium strain the cell.

   too little — If little selenide is available, all following steps stall at once, because every selenoprotein is built from this one pool.

   observed in studies · Source 2

2. Selenide → Selenophosphate SEPHS2 · ATP Selenophosphate synthetase 2 attaches selenide to a phosphate from ATP. Only in this form can selenium be built into proteins. Without ATP no selenium enters the selenoproteins. Source 2↑ supplies Selenophosphate is the only form in which the cell provides selenium for incorporation. The reaction uses ATP; without it no selenium enters selenoproteins, however much selenide is present. established physiology Source 2
   ⚖ When the balance tips

   too much — More selenophosphate does not bring unlimited incorporation: the amount of selenocysteine tRNA and the reading steps at the ribosome set the limit.

   too little — If little selenophosphate is available, less selenocysteine forms on the tRNA, and all selenoproteins are replenished more slowly.

   established physiology · Source 2

3. Selenophosphate → Selenocysteine on tRNA SEPSECS · Serine on tRNA, PSTK Serine is first bound to a dedicated transfer RNA, phosphorylated and then converted into selenocysteine with selenophosphate by the enzyme SEPSECS. When little selenium is available, the most important selenoproteins are served first. Source 2↑ supplies The loaded tRNA brings selenocysteine to the ribosomes. It is the bottleneck between the selenium pool and the number of selenoproteins a cell can make. established physiology Source 2
   ⚖ When the balance tips

   too much — If plenty of loaded tRNA is present, all selenoproteins are made up to their full amount; beyond that their number does not rise further.

   too little — If little loaded tRNA is available, the cell keeps making housekeeping selenoproteins such as GPX4 and the thioredoxin reductases, while others such as GPX1 fall markedly.

   established physiology · Source 2

4. Selenocysteine on tRNA → Selenoprotein P Insertion at UGA codon · SECIS element When reading the genetic code, the cell inserts selenocysteine at the UGA codon; a signal in the RNA (SECIS element) makes this possible. The liver releases selenoprotein P into the blood; it carries selenium to the tissues. It falls early with low supply. Source 3, 1↑ supplies Selenoprotein P carries up to ten selenocysteines and is the vehicle for selenium in the blood. It brings selenium from the liver to tissues such as the brain, testes and kidneys. established physiology Source 3, 1
   ⚖ When the balance tips

   too much — With good supply, selenoprotein P in the blood reaches saturation: further intake hardly raises it; additional selenium then appears as selenomethionine in other proteins and in the urine.

   too little — If little selenium arrives, selenoprotein P in the blood falls early and markedly; the liver releases less, and tissues with their own receptor, such as the brain, keep their selenium longest.

   established physiology · Source 3

5. Selenium in the cell → Glutathione peroxidases This enzyme family carries selenocysteine in its active centre. It converts hydrogen peroxide and other peroxides into water. It uses up glutathione; if it works more slowly, peroxides persist longer. Source 4, 2↓ depletes The glutathione peroxidases break down peroxides before they alter membrane fats and proteins; GPX4 defuses lipid peroxides directly in the cell membrane. To do so they use up glutathione. established physiology Source 4, 2
   ⚖ When the balance tips

   too much — If peroxidase activity is high, hydrogen peroxide that the cell uses in small amounts as a messenger is also intercepted; this signal then becomes weaker.

   too little — If the glutathione peroxidases work more slowly, peroxides persist longer and alter fats in the membranes; in cell culture and animal models, cells without GPX4 activity are not viable.

   observed in studies · Source 4

6. Selenium in the cell → Deiodinases The deiodinases also carry selenocysteine. They remove single iodine atoms from thyroid hormones and so determine which form is present in the tissue. When little selenium is available, they are made preferentially for a long time. Source 5↕ both, depending on amount The deiodinases determine how much active T3 is present in the tissue: DIO1 and DIO2 make T3 from T4, DIO3 converts T4 and T3 into inactive forms. Each tissue thus controls its own hormone action. established physiology Source 5
   ⚖ When the balance tips

   too much — If DIO3 activity predominates, more T4 and T3 are inactivated, and less hormone action reaches the tissue even if the thyroid releases enough.

   too little — If little selenium is available, the deiodinases are made in preference to other selenoproteins for a long time; if their activity still declines, T4 is converted to T3 more slowly.

   established physiology · Source 5

7. Hydrogen peroxide → Water Glutathione peroxidase · Glutathione (GSH) Glutathione peroxidase transfers electrons from glutathione to the peroxide; water and oxidised glutathione remain. Glutathione reductase regenerates GSH from the oxidised glutathione using NADPH. Source 4↑ supplies At the end there are water and oxidised glutathione (GSSG). Glutathione reductase regenerates GSH from GSSG with NADPH, so the cycle can continue. established physiology Source 4
   ⚖ When the balance tips

   too much — If a lot of oxidised glutathione accumulates, the GSH to GSSG ratio shifts – a sign that a lot of peroxide is currently being broken down.

   too little — If little glutathione is recovered, for example because NADPH is scarce, the peroxidase has fewer electron donors and the breakdown of peroxides slows.

   established physiology · Source 4

8. Thyroxine (T4) → Triiodothyronine (T3) Deiodinase Deiodinases remove one iodine atom, forming T3, which binds to receptor sites in the cell nucleus. Other deiodinases convert the hormones into inactive forms. T3 helps set energy turnover, heat production and heart rate. Source 5↑ supplies T3 binds to receptors in the cell nucleus and switches on and off genes that set energy turnover, heat production and heart rate. How much T3 reaches a cell is regulated locally by the deiodinases. established physiology Source 5
   ⚖ When the balance tips

   too much — If a lot of T3 is present in the tissue, energy turnover, heat production and heartbeat speed up; DIO3 then increasingly converts T3 into inactive forms.

   too little — If little T3 is present in the tissue, energy turnover and heat production slow down, and the genes concerned are read less often.

   established physiology · Source 5

9. Selenoprotein P → SELENOP + autoantibody · autoantibody (IgG) Some people form autoantibodies against selenoprotein P. They bind to the transport protein in the blood; they are measured separately from selenoprotein P itself. Source 6↓ depletes In cell experiments such autoantibodies inhibited the uptake of selenium via selenoprotein P; once bound, the transport protein reaches its receptors less well. observed in studies Source 6
   ⚖ When the balance tips

   too much — If a lot of selenoprotein P is bound, less selenium reaches the tissues; in studies, autoantibodies went along with lower activity of the glutathione peroxidase GPX3 in the blood.

   too little — If such autoantibodies are absent, selenoprotein P reaches its receptors unhindered, and tissue supply follows the selenium intake alone.

   observed in studies · Source 6, 7

   Field of research — Autoantibodies against selenoprotein P are studied in thyroid disorders and in persistent fatigue. Source 6, 7

Further stations

• Selenium in food — selenomethionine, -cysteine In food, selenium is mostly built into amino acids, as selenomethionine or selenocysteine. In water and soil it also occurs as selenate and selenite. Selenomethionine serves as an interim store. Source 1↑ supplies The body builds selenomethionine into any protein in place of methionine and thus stores selenium temporarily; selenocysteine and inorganic selenium go straight into the path to selenide. Both feed the same pool. established physiology Source 1
  ⚖ When the balance tips

  too much — If more selenium arrives than the selenoproteins need, the liver converts the excess into methylated forms; they leave via the urine and, in large amounts, also via the breath.

  too little — If little selenium arrives, it is distributed by rank: some selenoproteins and organs such as the brain and testes are supplied first, the rest get what is left.

  established physiology · Source 1

• Selenium in the cell — taken up via ApoER2 Cells bring selenoprotein P inside via receptors such as ApoER2 and release the selenium from it. From this they build their own selenoproteins. The brain and testes are supplied preferentially. Source 3, 1↑ supplies Via receptors such as ApoER2 or megalin, the cell absorbs selenoprotein P and breaks it down. The released selenium goes via selenide into the cell's own selenoproteins. established physiology Source 3
  ⚖ When the balance tips

  too much — If more selenium is available than the cell can build into selenoproteins, the excess goes into methylation and is excreted.

  too little — Tissues with ApoER2, such as the brain and testes, draw selenium preferentially even when supply is scarce; tissues without this receptor then get less.

  established physiology · Source 3, 1

• Hydrogen peroxide — formed in metabolism Hydrogen peroxide arises in many reactions in the cell and can alter proteins and membrane lipids. In small amounts it is also a signalling substance of the cell. Source 4↕ both, depending on amount Hydrogen peroxide is both: in small amounts a signalling substance that switches enzymes on and off, in larger amounts it alters proteins, fats and DNA. The peroxidases keep it within the signalling range. observed in studies Source 4
  ⚖ When the balance tips

  too much — If hydrogen peroxide builds up, it oxidises sulphur groups in proteins and fats in membranes; further peroxides form from the fats and continue the chain.

  too little — If there is very little hydrogen peroxide, signals are missing by which cells respond, for example, to growth factors; a cell is never entirely free of it.

  observed in studies · Source 4

• Thyroxine (T4) — storage form The thyroid releases mainly thyroxine. It carries four iodine atoms and itself acts only weakly at the cell’s receptor sites. Only in the tissue is it converted to T3 as needed. Source 5↑ supplies T4 is the storage and transport form: it circulates in the blood for a long time and is converted to T3 only in the tissue as needed. Each organ thus sets its supply independently of the blood level. established physiology Source 5
  ⚖ When the balance tips

  too much — If a lot of T4 is present, tissues reduce DIO2 activity and increase DIO3; less of it is then converted to T3 and more is inactivated.

  too little — If little T4 arrives, tissues such as the brain increase DIO2 activity and make more T3 from the available T4 to maintain their supply.

  established physiology · Source 5

Cofactors in this pathway

• Glutathione — Supplies glutathione peroxidase with the electrons it uses to convert peroxides to water; without it, breakdown stalls Source 4In the ORY catalogue as a laboratory value: Glutathion (GSH)
• Iodine — The selenium-containing deiodinases remove iodine atoms from T4 and T3 and so determine how much T3 acts in the tissue Source 5In the ORY catalogue as a laboratory value: Jod (Urin)
• Serine — Converted into selenocysteine on its own tRNA; without serine no selenocysteine forms Source 2In the ORY catalogue as a laboratory value: Serin
• Vitamin B6 (PLP) — Cofactor of selenocysteine lyase, which releases selenium as selenide; with little PLP, less selenium is released Source 1, 2In the ORY catalogue as a laboratory value: Vitamin B6
• ATP — Provides the phosphate with which SEPHS2 activates selenide to selenophosphate; without ATP no selenium is built in Source 2
• NADPH — Electron donor for the thioredoxin reductases, which are themselves selenoproteins; also for recovering glutathione Source 2

Sources

1. Burk RF, Hill KE. Regulation of Selenium Metabolism and Transport. Annu Rev Nutr 2015 · PubMed 25974694
2. Labunskyy VM, Hatfield DL, Gladyshev VN. Selenoproteins: molecular pathways and physiological roles. Physiol Rev 2014 · PubMed 24987004
3. Schomburg L. Selenoprotein P - Selenium transport protein, enzyme and biomarker of selenium status. Free Radic Biol Med 2022 · PubMed 36067902
4. Brigelius-Flohé R, Maiorino M. Glutathione peroxidases. Biochim Biophys Acta 2013 · PubMed 23201771
5. Köhrle J. Deiodinases control local cellular and systemic thyroid hormone availability. Free Radic Biol Med 2022 · PubMed 36206932
6. Sun Q, Mehl S, Renko K et al. Natural Autoimmunity to Selenoprotein P Impairs Selenium Transport in Hashimoto's Thyroiditis. Int J Mol Sci 2021 · PubMed 34884891
7. Sun Q, Oltra E, Dijck-Brouwer DAJ et al. Autoantibodies to selenoprotein P in chronic fatigue syndrome suggest selenium transport impairment and acquired resistance to thyroid hormone. Redox Biol 2023 · PubMed 37423160

Whole pathway: Selenium

Related pathways

• 8-OHdG — hydrogen peroxide
• Glutathione — hydrogen peroxide
• Antioxidant capacity — hydrogen peroxide
• Folic acid — Serin, Vitamin B6
• IgE antibodies and mast cells — Glutathion (GSH), Vitamin B6

As of 2026-09-16. Draft written by Claude to schema v2; sources checked in PubMed; expert review pending
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