Image - Molecular Structure of Selenocysteine
Molecular Structure of Selenocysteine

Let’s discuss about Selenocysteine – an amino acid which takes part in the production of some very important proteins in our body, but the medical biochemistry books are quite deficient of information regarding it. So this article will specifically be on the medical significance of Selenocysteine.


Why is it called Selenocysteine?

It has the same molecular structure of Cysteine amino acid except the Sulfur (S) group is replaced by Selenium (Se). Se is just below the S in the 16th group in the periodic table. They share many chemical properties including the valence. So it’s not too surprising if one of them replaces the other in a compound under specific conditions.


Image Showing the position of Sulfur and Selenium in Periodic Table
Position of S and Se


Why is it called 21st amino acid?

Before its discovery the known protein-forming amino acid pool contained 20 amino acids. They are listed in the image below. So it’s discovery introduced us the 21st member of proteogenic amino acid pool.



N.B. The name “21st amino acid” may be misleading, as Selenocysteine actually is the 21st PROTEOGENIC amino acid.


Image - 21 Proteogenic Amino Acids
21 Proteogenic Amino Acids


So now there are 21 proteogenic amino acids…right?

Actually, there are 22 of them discovered till now. The last one is named Pyrrolysine, but it makes proteins only in prokaryotes (methanogenic archaea and bacteria).


So is there any other amino acids that are not “PROTEOGENIC”?

The proteogenic pool of amino acid is only a small part of the whole amino acid pool. There are many times more amino acids that don’t produce proteins. Usually, the amino acids that don’t have any associated genetic code won’t produce proteins (they can’t take part in translation), and so are non-proteogenic.

This is quite logical. Any organic molecule having at least one of each amine and carboxyl group can be called an amino acid and we have only limited number of genetic codes.

Examples of non-proteogenic amino acids are – ornithine, citrulline etc. in hepatic metabolism. The argininosuccinic acid in the urea cycle, S-adenosylmethionine, azaserine in streptomycin, synthetically produced (at least commercially) penicillamine, somewhat controversial taurine etc.


What is the genetic code of selenocysteine?

The genetic code for selenocysteine is UGA. You may have noticed that it’s a stop codon, the other two being UAA and UAG. Another interesting finding is that the code for 22nd proteogenic amino acid pyrrolysine is carried by UAG stop codon. Quite clearly in both of these cases, these codons are not acting as stop codons…they encode for these specific amino acids.


You may have noticed that this change in function of UGA or UAG brings out an astonishing exception in the concept of the genetic code. All codons specifically code for one single amino acid (or makes a single meaning to the translating machinery). Though there may be multiple codons for a single amino acid, in this case, both the codons UGA and UAG means both stop signal as well as these amino acids.


So what causes the stop codons to change their function?

There are stem-loop sequences (parts of RNA containing both base-pairing and non-base pairing parts) in the mRNA for the proteins containing those specific amino acids. In the case of selenocysteine, it is called SECIS (SElenoCysteine Insertion Sequence) element and in the case of pyrrolysine called PYLIS downstream sequence. These sequences determine whether any tRNA would bind to the ribosome when the stop codon reaches its A-site.


Image - SECIS sequence


The tRNA for selenocysteine is different both in structure and function from other amino acid tRNAs. Selenium being a biologically reactive element is stored in Selenide form. During translation, the selenocysteine specific tRNA takes up a cysteine molecule and get attached to the ribosome. Then another enzyme comes and replaces the sulfur (in cysteine) with selenium.



What are the proteins that contain selenocysteine?

These proteins are called selenoproteins. They are being discovered till now. Examples of well-known selenoproteins in human beings are –

Image - PHYLIS Sequence


  1. Glutathione peroxidase
  2. Iodothyronine deiodinases
  3. Selenoprotein-P, -R, -S etc.
  4. Glycine reductase
  5. Thioredoxin reductases etc.



Arnab Mukherjee

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Further Reading

  1. A Forgotten Debate: Is Selenocysteine the 21st Amino Acid?,
  2. Biosynthesis of Selenocysteine, the 21st Amino Acid in the Genetic Code, and a Novel Pathway for Cysteine Biosynthesis,

  3. Selenocysteine Synthase,


Image Attributions

  1. 21 Amino Acids – By DancojocariOwn workPrint It HereThis vector graphics image was created with Adobe Illustrator.iThe source code of this SVG is valid., CC BY-SA 3.0, Link
  2. Position of S and Se – By Arnab Mukherjee.
  3. Molecular Structure of Selenocysteine – By YassineMrabetThis vector image was created with Inkscape.This image was created with PyMOLOwn work, CC BY 3.0, Link
  4. SECIS – This image is taken from the Rfam database, Public Domain, Link
  5. PYLIS – By Rfam – Rfam, Public Domain, Link


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One Comment

  • Anonymous Reply

    Wow, great. I had a question…what about Selenocysteine metabolism? How is it degraded?

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