What's wrong with Na+ ions?

Raphi asked a very interesting question in the comments section of the last post:

"Could you please expand on why you *think* Nick Lane might think what he does here?"

"[...] he seems wedded to proton translocation as being physically related to ferredoxin reduction, which I doubt is needed. It's not a "reduced FeS synthase-like" machine, as far as I can see. The generation of formate under simulated vent conditions needs nothing other than a completely randomly structured amorphous Fe/NiS matrix, nothing cell-like or translocating is required for this aspect in Lane's bench top reactor."

There are two aspects to this. One is the specificity of early life for protons, i.e. do we have to have a gradient of protons, and the other is what sort of process is involved in the generation of the thioester which is the precursor of acetyl CoA. Is there an "FeS-synthase" machine?

This current post is about the Na+ gradient aspect.

Nick Lane’s basic objection to the use of Na+ ions is that the the concentration of the ocean is very high, so to make a difference at the membrane you have to pump a lot more Na+ than H+. His exact footnote from The Vital Question is:

“The alert reader may be wondering why the cells don't just pump Na+? Indeed it is better to pump Na+ across a leaky membrane than to pump H+, but as the membrane becomes less permeable, that advantage is lost. The reason is esoteric. The power available to a cell depends on the concentration difference between the two sides of the membrane, not on the absolute concentration of ions. Because Na+ concentration is so high in the oceans, to maintain an equivalent three orders of magnitude difference between the inside and outside of the cell requires pumping a lot more Na+ than H+, undermining the advantage of pumping Na+ if the membrane is relatively impermeable to both ions”.

I have a lot of problems with this standpoint. First is that you are not trying to increase the extra cellular Na+. A few extra Na+ ions in the ocean, perhaps already at a sodium ion concentration of 450mmol/l in the region of a protocell, are hardly going to change the Na+ concentration around that protocell. I would regard the primordial extra cellular Na+ concentration as fixed. What you actually have to do is to drop the intra cellular Na+ concentration to 1/1000th the ocean concentration and you would then get those three orders of magnitude in to the gradient. Somewhere just under 0.5mmol/l within a cell versus an ocean at 450mmol/l outside the cell would do this.

This leads directly to the second problem I see. This is the concept that you might remotely need a 10^3 Na+ gradient.

The function of the 10^3 proton gradient provided by the vents, in the beginning and in Nick Lane’s reactor, is to provide FeS at a redox potential to reduce CO2 to CO using H2. That needs a big proton gradient.

Pumping Na+ ions is completely different. No one is talking about reducing FeS using Na+ ions. All the Na+ gradient is doing is trying to store energetic loose change to make a few ATP molecules. This does not need a 10^3 Na+ gradient. Acetobacterium woodii will grow with an extracellular Na+ concentration of about 50mmol/l, well below the speculated 450mmol/l of the primordial ocean. There is no way A woodii can generate a 10^3 Na+ gradient with 50mmol/l extracellular Na+ and A woodii grows quite nicely on very modest Na+ energetics. These energetics are completely dependent on an ATP synthase driven by a gradient of Na+ ions but this doesn't need a 10^3 Na+ gradient.

My third problem is that all of this only applies once ATP synthase becomes active as a synthase. I can't visualise a complex rotator stator evolving to run on a primordial H+ gradient. While both the pore-like structure and the ATP consuming helicase component appear to be very highly conserved across the archaea-bacterial divide, the method of joining these two common subunits together to form an ATP synthase is certainly not conserved. My conclusion from this is that while the precursor of ATP synthase was a component of LUCA, ATP synthase itself was not. If ATP synthase is not primordial there is no specific need for it to be running off of the primordial proton gradient. I described Koonin's idea that ATP synthase develop from a translocase in a previous post.

If we accept Koonin's concept as correct about the pore/helicase scenario and the functional role of Na+ ions in stabilising the pore structure, this naturally leads to the expulsion of Na+ ions from the cell without any clear cut benefit other than lowering the intracellular Na+ concentration.

I initially had no idea what the the benefit of a low intracellular Na+ concentration might be. Obviously ATP synthase would not be retained as a pump of Na+ ions unless there was some immediate benefit to the cell. Now I might have found a potential benefit to lowering intracellular Na+ which applies to the primordial generation of acetyl thioester which is core to substrate level phosphorylation at the start of life and has direct relevance to the use of the proton gradient.

The more I think about it the more it seems likely that there actually was a molecular machine running off of the proton gradient soon after the start of "life". But I do not think it was anything like ATP synthase, i.e. there are no molecular mechanics, no protons pushing bits of protein around in the way protons do in a modern ATP synthase.

How it all came together is an interesting area to speculate on. Perhaps in the next post.

Peter