Life (33) Transient hunger

Just a brief repeat that the origin of metabolism is this reaction at

pH 6:

CO₂ + 2e- + E(in) -> CO + O^2-

where the electrons and activating energy E(in) come from molecular hydrogen in solution at pH 10.

The next step is:

CO + O^2- + 2H⁺ -> HCOOH + E(out)

where E(out) is greater than E(in) , making the reaction exothermic and not reversible without the input of energy. Because there is no system for resupplying this energy to drive the reaction in reverse, you cannot convert the hydrocarbons back to molecular hydrogen and CO₂. Once the proto-metabolite hydrocarbons are formed they are stable and so able to accumulate as the building blocks of life. It's a one way process.

Biomolecules accumulate. They are energetically stable.

So if we look at these conditions:

there is no need for localised stability, the wiggly line of the interface can move left or right at random. So long as there is an interface, biomolecules will form, be stable and so accumulate.

That's step one.

Next comes the development of another use for the energy provided by hydrogen at an alkaline pH.

A very, very early product of evolution was the development of the ferredoxin (Fd) molecule, an FeS cluster bound to one of the most ancient but tightly conserved very small proteins on earth. It allows the capture of both the electrons and the activation energy from our primordial hydrogen source in to a storable form, rather than it being used immediately to fix CO₂. Again the electrons and energy come from hydrogen at pH 10, as per hydrocarbon formation.

Ferredoxin + 2e- + E(in) -> Ferredoxin^2-

If we take out all intermediate steps we can summarise the generation of Fd^2- near the origin of life like this

H₂ + Fd -> Fd^2- + 2H⁺

Fd^2- (reduced ferredoxin) can supply electrons and energy to drive metabolic processes throughout the protocell, well away from the site where pH gradient recapitulation is driving hydrogen oxidation. I think ferredoxin came well before ATP arrived but it did, and still does do, the same job.

This cannot happen in the core primordial situation. High energy ferredoxin in the presence of a catalyst would react with random protons immediately to regenerate molecular hydrogen and heat. Stability of Fd^2- requires a cell membrane to protect it from the catalytic primordial FeS and NiFeS surface.

This happens automatically when organics accumulate as a coating to the acidic area of the protocell surface. So now an amino acid derived "tube" is needed to get the pH 6 fluid in to the cell and the NiFeS and FeS clusters need to be embedded in some sort of amino acid derived structure to hold them in the correct pH zones. Like this:

which is the basis of this:

which we can declutter to this:

We are now in a position to speculate about what might happen in a protocell which experiences fluctuations in the supply of hydrogen rich alkaline vent fluid. Loss of vent fluid allows the pH of the protocell to drop towards the acidic pH 6 of the ocean, shown as the red alkaline fluid in the above doodle turning to a more blue acidic fluid, as here below:

Recall that organic molecules are safe from degradation under these circumstances but that ferredoxin is not. So it is very easy to degrade Fd^2- to molecular hydrogen, losing some of its stored energy as heat energy. Note the reversal of the arrows in the above diagram as this happens.

If this is a short term fluctuation there is the potential to preserve on-going protocell function in two ways. One is to stop the flow of electrons derived from Fd^2- jumping from the embedded FeS cluster to the embedded NiFeS cluster. All that is needed is either a conformational change to the NiFeS structure to move it physically away from the FeS cluster or to change its local environment to make it an unattractive target for electrons. Changing the shape of a protein in response to protonation is a very simple concept and I've illustrated in this next doodle where the acidified NiFeS support structure has moved the NiFeS cluster away from the FeS cluster due to such a shape change.

This stops the wasteful generation of molecular hydrogen from Fd^2-.

The second technique is to limit the ingress of protons from the acidic ocean fluid.

We currently have a situation where electrons are still free to travel from Fd^2- to the embedded FeS cluster, producing a net negative charge:

All that is now needed is a positively charged area of amino acids in the transmembrane tube structure, like this:

and we now have the potential to alter the shape of the transmembrane tube to stop the ingress of protons from the oceanic fluid. All that is needed is for a positively charged localised area of the transmembrane tube to move towards the now negatively charged FeS cluster and produce a conformational change. This can limit acidic fluid ingress and preserve whatever alkaline conditions are still present within the protocell. Note the reinstatement/preservation of some degree of red alkaline pH-ness in to the intracellular fluid zone and lack of blue acidic pH-ness in the protocell area of the catalytic FeS cluster:

This provides a temporary "pro-survival" state for the protocell using the remaining Fd^2- pool while awaiting the prompt (hopefully) return of vent fluid. Return of vent fluid's alkaline conditions removes protonation of the area around the NiFeS cluster, returning it to close proximity of the FeS cluster and establishing electron flow from the now resupplied hydrogen to the now depleted Fd^2- pool. This opens the transmembrane channel and allows normal cell function to return:

and we're back where we started from.

These thoughts came from a combination of Nick Lane's comment about the protonation of Ech (also read MBH, complex I or about 6 other membrane pumps from the same family) in the region of a transmembrane channel coupled with some degree of reverse engineering of complex I mechanism in these two papers, which are another post but if anyone wants to read ahead they're here:

Symmetry-related proton transfer pathways in respiratory complex I

especially figures 2A and 6

and here:

The coupling mechanism of respiratory complex I — A structural and evolutionary perspective

also figure 6 and the associated legend.

It's all about what is reversible and what is not. The above doodles describe a pre-adaptation to a situation where reversal will lead to proton pumping. They're not describing a pump per se but they provide the basis for a pump should that become advantageous.

Peter