Xenon as an Everyday Indispensable Ligand

A couple of times, and that is plenty, I've had pointless discussions with people who themselves thought they were having victorious arguments, on the subject of substances so dilute their postulated biological effects had to exist. Precisely because such (unnamed) substances were impossible to measure, I was supposed to accept that they were capable of anything. No, I don't accept any such thing: you have to demonstrate it, and until you do, I don't care. Fortunately, one interlocutor was a longtime friend and the other a spare-time door-to-door political canvasser, and in both cases both of us were late for supper, so acrimony was minimal. And the idea's half-formedness is forgivable. It isn't wrong from the get-go; it just needs a lot of work. Below nutrients, micronutrients, and ultramicronutrients, is there yet another category of a-molecule-here-and-there nutrients?

Xenon isn't a nutrient, but under certain circumstances it has at least one biological effect (anesthesia) and it is known to bind to various proteins in measurable amounts at predictable points. It does what it is currently known to do only when delivered at concentrations well above its natural occurrence in air. But it is everywhere, every living thing must have a little inside it, getting all of it out of a living thing in order to test the consequences of its absence cannot be an easy experiment, and some xenon must be lodged on some biomolecules at any given time in any given lifetime. Might these very occasional and/or fleeting visitations be biologically significant?

Imagine the "biological significance" is that xenon's job is not to help something salubrious do its bit, but rather to keep something noxious off, or out, or prevent something noxious from ever being built. Xenon might be good for this: its concentration is steady and reliably low, no one's ever going to run out of it, and this kind of job suits a material that is after all inert. So, how might it do this?

1. A xenon atom - maybe just one - lodges itself within DNA, with very high affinity, and prevents RNA polymerases from working. Which is presumably good, because the gene product is postulated to be bad.
2. A transmembrane pore, and a very long one at that, has multiple binding sites for xenon. If just one binds, at any one of these, the pore is blocked. And again that is supposed to be good, because what's kept out is something bad.
3. A protein needs to oligomerize in order to form something functional - and bad - but just one xenon gets in the way of this.
4. A protein becomes harmful if some very large and very rigid ligand binds to it, and just one xenon atom blocks just enough of the site to keep the ligand off. That is, xenon is very much smaller than the ligand but can occupy any one of a great number of spots within the site.
5. A harmful protein needs to fold itself, through a very long series of steps, at any one of which just one xenon atom can fatallly interfere.

I like the last idea most, though there is no evidence for any of these ideas. Number 4 has some attraction, since steroid molecules (I imagine) form a large number of weak bonds with whatever they stick to, and the only way to make this thermodynamically tenable is for steroid molecules to be pretty stiff: they must lose little entropy upon binding. But I think with xenon, whose physiological concentration is probably nanomolar and whose binding constants with just about anything are probably millimolar at best, you'd need to picture a binding site with hundreds or thousands of contact points, as well as a ligand so broad and so braced that just "one stone in the shoe" is too painful. The bond formed at each contact point must be so weak that the loss of just one to an intruding xenon atom makes overall binding thermodynamically unfavorable.

Interference with protein folding is more plausible, if the kinetics are right. Depends on the protein. Also depends on how fast a xenon atom can get on or off the protein. Waving my hands, I picture a peptide which beccomes biologically significant only after its two ends meet and fold into an active site. The two ends being very far apart, there is little chance of them coming together on their own. The peptide must fold, starting at its midpoint and zipping its way up until the ends are finally brought together. I imagine such a peptide to be mostly hydrophobic amino acids, mostly aprotic ones too - Phe, Val, Leu, and Ile, I'd guess, ones with bulky side groups so as not to give the peptide chain too much rotational freedom, but not "interesting" enough to engage in more than van der Waals attractions with neighbors (or solvent molecules). I presume also that hydrophobic amino acids are what xenon usually sticks to. Neither enthalpy nor entropy should change much, the net has to be just barely in favor of folding, and just one xenon anywhere should be enough to spoil it.