Selenocysteine looks like cysteine, but with selenium instead of sulfur. Sulfur vs. selenium may not seem like a big deal, but it matters a lot when there are electrons to steal! And it might be rare, but Selenium (Se)’s chemical properties can imbue electron give-take-ing abilities to proteins, allowing our body’s natural antioxidant system to protect us from high-energy reactive oxygen species (ROS). And selenocysteine is special in another way - it’s able to “fool” our “foolproof” protein-making machinery into adding it instead of stopping. full text: [ Ссылка ]
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Selenocysteine's sidechain is a -CH₂-SeH group. -SeH is called a SELENOL & it’s more generous with its H⁺, as evidenced by it’s lower pKa. pKa is a measure of acid strength (more here [ Ссылка ]). The lower the pKa, the stronger the acid (it will give up an H⁺ more readily). pH is a measure of “free” H⁺ At a pH above a molecule’s pKa, there are fewer extra H⁺, so even a stingier acid will start to feel “guilty” and donate to the cause - it’s more likely to be deprotonated at a pH above the pKa (more basic/alkaline conditions) & below the pKa (more acidic conditions) it’s more likely to be protonated (there are plenty of free H⁺ around, why should I share?)⠀
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Se gives up an H⁺ more easily than S (in science-y terms we say it’s more acidic & has a lower pKa (the pKa of Sec is ~5.2 vs. 8.3 for Cys). The pH of our cells is ~7.4, which is above Sel’s pKa but below Cys’, so Cys is likely in its protonated thiol form (protein)-SH, BUT Sel is likely in it’s proton-less selenate form (protein)-Se⁻⠀
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Atoms are more stable when they’re neutral, but H leaves as a proton (H⁺) leaving behind its e⁻ and unbalancing the charge. Sel’s Se⁻ doesn’t like being charged - it only gave up an H⁺ because it saw that others needed it (well, not technically - it’s more like it just always loses it more easily and now there are less new ones to find when it does) So it will jump at the chance to get some positivity to even out its negativity. And where can you find positivity? In a nucleus (where the positive protons are) - so we call selenate a NUCLEOPHILE. [ Ссылка ]
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As a nucleophile, it will seek out & attack ELECTROPHILES (partially or fully charged things that want more e⁻) & form new bonds with them. BUT, it’s also more likely than S to lose those new bonds it forms. Why such a fair-weather friend?⠀
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S “needs” a partner more than Se does. Because Se’s bigger, it’s better able to spread out the extra charge that comes w/splitting up (think of a drop of food coloring in a pool vs a cup). It feels the loss of a partner less so is better able to cope without it. Additionally, just like it’s awkward for someone with a giant hand to shake a little kid’s hand, it’s awkward for a big atom like Se to form bonds w/smaller things, so the bonds it forms are weaker. Therefore, you wouldn’t want to rely on Sec-Sec bridges to hold a protein together outside the cell or Sec to hold on tight to an important metal ion (things Cys is good for) BUT the reversibility makes Sel a great sensor & protects proteins from “permanent” oxidative damage.⠀
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Going back to breaking up a disulfide bridge - you need a reducing agent & selenate (the -Se⁻ form) can step up to the plate! Remember, it has more e⁻ than it wants & oxidation is loss of e⁻. So it wants to be oxidized (which means something else has to be reduced, since you can’t have one without the other!) Therefore, it breaks up the disulfide bond by latching onto one of the S’s. But now you have a Se stuck to the S (a selenenylsulfide (1 Se & 1 S) instead of a disulfide (2 S’s)). (instead of protein-SH & HS-protein you have protein-S-Se-protein & HS-protein) Thankfully, that Se-S bond’s weaker than the S-S bond was so it can break off easier, giving you 2 reduced cysteines⠀
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Glutathione peroxidases (GpX’s) were the first identified selenoproteins & they’re one of the first lines of defense against oxidative stress. They catalyze (mediate & speed up) reduction of hydrogen peroxide (H₂O₂) &/or lipid peroxides to water & lipid alcohols with the help of glutathione. GpX’s selenol (GPx–SeH) reacts with the peroxide, neutralizing that threat but by grabbing one of its Os, and turning into selenic acid (GPx–SeOH) in the process. To get back to where it started, it latches onto glutathione’s sulfur, trapping it in a glutathionylated intermediate (GPx–Se–S–G) which then reacts with another glutathione & the glutathiones, now in the oxidized form (GSSG), leave together, giving you the selenol form again.⠀
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Other important selenoproteins are thioredoxin reductases (TrxRs), which work with little proteins called thioredoxin (Trx) to serve as an intracellular disulfide reduction squad to regenerate antioxidants and help regulate signaling pathways. TrxR’s Sec helps replenish Trx’s Cys’s. And iodothyronine deiodinases are involved in making thyroid hormones⠀

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