Tuesday, June 23, 2015

Why sodium ions?

I will now try and shut up about the origins of life. But first I have to summarise the idea which threw itself at me as I tidied up the last post, before I can desist:

As a follow on to their ideas relating to the development of the ATP synthase complex, Koonin and his group have a paper suggesting that sodium bioenergetics were primordial to the origin of life. Happily, like their ATP synthase paper, it's free full text so people can make their own minds up as to how good the arguments appear. I think they may be correct.

They go on to suggest that the precursor to the ATP synthase complex used Na+ ions to stabilise the structure of its intra membrane section, derived from the membrane pore, and that it was these Na+ ions which were extruded as the changes occurred when a translocase became an ATP driven Na+ extruding motor.

I like this idea.


Koonin rejects a deep ocean origin of life scenario, largely on the premise that a high K+ environment within modern cells indicates that life started in a K+ rich environment. This has led him to land based geothermal ideas, foramide and Zn based photosynthesis. This is un necessary if we use his own Na+ pump to surmise a very early reduction in intracellular Na+ driven by ATP. No need for mud bubbles and foramide around a K+ rich geothermal vent...

Lane rejects Na+ only bioenergetics in a footnote on pages 146-8 of his latest book. The rejection is the weakest page in the whole text and he doesn't really explain it, excepting 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.

It dawned on me during the pre-posting tidy-up of the last post that you could use both ideas together.

Take Lane's ideas about a sustained source of reduced carbon compounds based on a pH differential, with a proton gradient being utterly essential for redox conditions but reject H+ translocation as being a mechanical essential for FeS reduction. What is needed is reduced FeS. This is available immediately, certainly within four hours, in the group's bench top reactor. Energetics would be based on formate and acetate, the later giving substrate level phosphorylation capable of yielding ATP.  For this scenario you have to reject a role for any sort of primordial H+ powered ATP synthase. This suits me.

What is then needed is some sort of support (I have none) for the idea that nascent metabolism occurs more effectively with a reduced sodium level within the cell. This might be testable. Quite how I don't know, but there are clever people out there that might have some ideas.

Assuming there is some net benefit to a cell from having lower Na+ levels within, then there is some benefit of the "accidental" generation of a sodium pump based on Koonin's scenario of ATP synthase formation. This makes ATP synthase in to the primordial Na+ pump, at the cost of ATP consumption. That's OK in a vent as ATP is fairly free, provided by the H+ gradient via acetyl phosphate. Though there might be better uses for the ATP if ATP-consuming pumping wasn't needed.

Subsequent development of a Na+/H+ anti porter would radically drop the Na+ concentration within the protocell, and it would do it completely for free, without needing to divert ATP to pumping. The rapid drop in intracellular Na+ then reverses the outward pumping of Na+ by ATP synthase which then allows ATP generation at the cost of allowing Na+ back in to the cell. This can be continuously corrected by the anti porter. The low Na+ intracellular environment then becomes beneficial in its own right and drives subsequent evolution to tailor protein function to run best run in a high K+, high Mg2+ and low Na+ environment.

To escape the vent H+ gradient the anti porter then needs to be converted to be driven by reduced ferredoxin from electron bifurcation rather than from a proton gradient based redox potential and away we go.

Just thinking. Makes sense of both camps.

I'll try and shut up about the origins of life now.

Peter

PS Conversion from Na+ to H+ pumping has occurred on several different occasions in microbial evolution. It's quite easy to drive ATP synthase by either ion, given the similarity in size and charge between the Na+ ion and the hydrated H+ ion, H3O+. The drive for H+ energetics appears to have been the development of redox chains with cytochromes, which are totally proton dependent. Nick Lane's ideas that Na+ energetics are limited to extremophile or acetate rich environments does not hold true for Na+ pumpers in the anoxic deep mud of Woods Bay. Simply evolving without cytochromes seems to be enough to preserve Na+ bioenergetics. Cytochromes are so powerful most organisms went that route. But not all.

Must. Shut. Up.

Peter

11 comments:

Richard B said...

Never shut up about the origin of life stuff! Its brilliant.

Having read through most of your blog more than once, especially the Proton series, but I am still a bit confused about some details.

Why exactly is beta-oxidation of long chain fatty acids better in terms of preserving mitochondrial function esp compared to glycolysis etc? It sort of eludes me, so I am missing something. I know you are more about investigation than preaching, but a summary of your position to date overall would be very useful. I promise not to take it as dogma.

Bob said...

"Must. Shut. Up."

Why? It's even further over my head than some of the more "conventional" stuff your write about. But, when I take the time to go through it carefully and repeatedly, it is interesting and makes reasonable sense.

Peter said...

Richard,

I have a whole stack of papers on mitochondrial biogenesis which life stopped me getting round to reading in detail . I suspect it will be a combination of superoxide generation through ETC input at electron transferring flavoprotein dehydrogenase causing reverse electron flow through complex I combined with a low cytoplasmic (i.e. nuclear) NADH:NAD+ ratio. i.e., markers that the ETC is struggling but there's not a terribly reduced cellular state, i.e. need more mitochondria...

Peter

Jack Kruse said...

I think K+ links to water by way or proteins because of Ling......so I am with Ling and Lane and not Koonin.

raphi said...

This paragraph was my Aha! light bulb moment on the importance of a low Na+ intracellular environment:

"Subsequent development of a Na+/H+ anti porter would radically drop the Na+ concentration within the protocell, and it would do it completely for free, without needing to divert ATP to pumping. The rapid drop in intracellular Na+ then reverses the outward pumping of Na+ by ATP synthase which then allows ATP generation at the cost of allowing Na+ back in to the cell. This can be continuously corrected by the anti porter. The low Na+ intracellular environment then becomes beneficial in its own right and drives subsequent evolution to tailor protein function to run best run in a high K+, high Mg2+ and low Na+ environment."

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."

What is it about ferredoxin reduction that would prefer an amorphous Fe/NiS matrix rather than reduction via proton translocation? Is it about reduction occurring via electron addition rather than proton removal?


Please continue on this Origins of Life thread - it's above anything else on the subject I've come across!

Peter said...

Raphi, I've drafted a couple of replies to this but I think I'll go back and re read exactly what he says in "The Vital Question" and in the Sousa paper. Might be a few days.

Peter

Peter said...

It's turning in to another post....

Peter

raphi said...

excellent! eagerly awaiting the follow-up

PS: what a pity I was studying (don't laugh) Italian & Management while at UCL and not there in the Science/Biology department - what a waste! Oh well...I'm repenting now haha

Caroline Spear said...

NOt related to you post and I need to ask.. how do you find out what fats are being used in an experiment? I refer to this http://www.nutraingredients-usa.com/Research/High-fat-diets-may-change-gut-microflora-and-signals-to-the-brain-Rat-data/?utm_source=newsletter_daily&utm_medium=email&utm_campaign=13-Jul-2015&c=o%2FwcmrThI2mgFYRrBdDQYw%3D%3D&p2&k=NIU-BBA-AM-Probiota

Which had me laughing as they refer to a high fat diet as being 34%!

MAny Thanks

Caroline Spear

Caroline Spear said...

I must finish reading Nick's first book..
Not related to you last post peter, but I don't know how else to contact you..
How do we find out what fats are used in experiments?
I refer to this one http://www.nutraingredients-usa.com/Research/High-fat-diets-may-change-gut-microflora-and-signals-to-the-brain-Rat-data/?utm_source=newsletter_daily&utm_medium=email&utm_campaign=13-Jul-2015&c=o%2FwcmrThI2mgFYRrBdDQYw%3D%3D&p2&k=NIU-BBA-AM-Probiota
Which says that the high fat diet is 34% ft.. high???
Many Thanks
Caroline

Peter said...

Hi Caroline, the definition of a high fat diet is that it is based on sucrose. No sucrose, not high fat! The exception is B6 mice and assorted rat strains which have been bred to get fat on a genuine high fat diet. Generaly that have problems with peroxisomal oxidation of VLC fatty acids, defects in acute insulin secretion and subsequent excess insulin secretion to try to control the subsequent hyperglycaemia. They have nothing to do with humans but massively expand our knowledge of the defects of the B6 mouse and similar rat strains. We know a great deal about B6 mice. All of it is basically useless for work with humans.

To find the actual fats used often involves digging through three layers of references to find that it was trans fat based Crisco... That's common!

Peter