Wednesday, May 20, 2015

Polyprenyl derivatives at the origin of life

I just wanted to put something down about the possible early membranes used by LUCA. There is a good case to be made for leaky membranes (certainly to protons) composed of polyprenyl phosphates. Here's the logic:

Start with the modern mevalonate pathway, from wiki.
















Now, let's butcher it down to its utter basics:



Isopentenyl pyrophosphate is the central cornerstone of polyprenyl phosphate generation by this reaction:


















You can make the polyprenyl phosphate lipid as long as you like, just add more isopentenyl derived units. This gives us the entry point, top centre, for this diagram:

















Down the left hand side we have the simple pathway to the archeal plasma membranes, as you might expect. Down the centre is the route to cholesterol, essential to animal cell membranes. The hopanoids, essential to bacteria but absent from archea, are left of centre.

Archea stayed with polyprenyls for their membrane, bacteria went for the fatty acids while retaining polyprenyl derived components. Derivatives of polyprenyls are ubiquitous. Metabolic cornerstones common to both archea and bacteria may well have been present in LUCA. Seems a reasonable argument to me.

There are a set of core enzymes present in both archea and bacteria which appear to have evolved before their divergence from LUCA. Perhaps the most significant is the rotator/stator ATP synthase, a piece of molecular nanotechnology of breathtaking complexity, considering that it appears to have evolved as one of the core early molecular machines of life. It's association with membranes suggest that membranes were there quite early on in evolution.

The presence of membranes allows us to think about some interesting questions. Such as why are cells powered by ATP? Because that is what ATP synthase produces. There is nothing intrinsically special about ATP. Reduced ferredoxin is a common power source in bacteria and archaea. Acetyl phosphate can be used too. But ATP is what is made by the ATP synthase machine and it can be produced in bulk, given a membrane potential. The hows and whys are interesting.

Peter

23 comments:

George Henderson said...

The polyprenyls are big in procaryotes too, giving us the terpenoids and carotenoids.

raphi said...

this is such cool detective work! really brings the story of the origins of life to...........life.

Yes, yes folks, I'm here all week!

Jack Kruse said...

I think Ling has the story correct on ATP. It is a chemical to move electrons to create a more negative net charge to change the redox potential of the CM and this allows for the construction of the exclusion zone of the intracellular water. This is how Gerald Pollack extended Ling's work. Ling thought structured water was a magnetic dipole but if that was true it should have a net zero charge. Pollack showed the world years ago the that exclusion zone in water excludes protons and it has a negative charge. This is a huge development in cell biology. I hope Peter gets back to the proton and electron story because Nick lane's latest book is pushing the boundaries toward this work. Peter's proton series was also headed there and then stopped. I have hope that Peter will read something in Lane, Pollack, or Khalili's latest works that stimulate his ideas further. Appreciate your insights you share Peter on your blog.

raphi said...

"Ling thought structured water was a magnetic dipole but if that was true it should have a net zero charge. Pollack showed the world years ago the that exclusion zone in water excludes protons and it has a negative charge. This is a huge development in cell biology." ==> I FINALLY have a basic understanding of how the EZ forms & that it's a charge separation without being a dipole.

In order to really get my head around the role of EZ water in cells...what example can you provide of a cellular function requiring EZ water which conventionally, we would otherwise think can occur without EZ water?

Does the negative charge in the mitochondrial cristae need it? Isn't it created by the proton gradient? Aren't we talking about about the (inner) cell membrane or is this at the level of every membrane, mitochondrial cristae included?

Also, how wouldn't the slightest EMF mess all this up? Where's the robusticity built in if EZ has the role it's purported to have?

Sorry for the stream of though question avalanche but I finally have some understanding to grasp. Granted, I haven't gotten around to Ling or Pollack yet...my bad.

Peter said...

Raphi, I read Ling's work many years ago. It's very simple to follow many of his arguments at the level of gelatin, it's OK to scale it up to conformational change in a single protein but I find it completely mind bending to try and visualise the TCA in his terms. It's beyond my classically educated mindset. I've said before in comments that water in cells is undoubtedly structured. But reading Pollack is in no way convincing that this is how life originated. I can see that water structure and water based metabolism come hand in hand. But I still buy in to concepts of nano machines with rotors, pores and conformational changes most easily describable in classical terms. Why make life difficult? Re origin of life: Pollack has to set up a reactor illuminated by green light which combines H2 with CO2 to give various derivatives on their way to methane. Even more overwhelming would be the conversion of CO2 to CO, which looks to be the core step in the derivation of acetate based metabolism. Nick Lane's group is very focused on methanogenesis, I think acetogenesis is closer to core utilisation of CO from reduced CO2...

Peter

Jack Kruse said...

Peter, Lane freely admits that both bacteria and Archea have wide diversity of metabolism.......yet he also says that diversity did not beget complexity of the eukaryotes. The key was the second pulse of the Great Oxidation when O2 tensions where raised high enough to build DHA in algae in the sea. DHA, O2 tensions, and eukaryotes are all linked to time. Here is the most interesting part Lane has not put together yet. Why is it that if we are to accept complexity and natural selection as the rule, has not DHA been replaced one time in eukaryotic cell membranes? Why is it in the eukaryotic kingdom that true animal and specifically mammal complexity is tied to the levels of DHA with the CNS and PNS of animals to allow it to control timing well? Here is the link: eukaryotic cells are loaded with internal double layered membranes that are jam packed with DHA.

Lane also says genes are not chimeric: His belief is clear in his latest book. The book is awesome but I think he left a lot of fat on and in the bone of where eukaryotic life came from. When you consider that 98% of the human genome is made from HERV viral parts I am not so sure Lane dogma fits the current evidence.

What ultimately could drive these processes? Highly powered energies from the environment that could inject energies into a cell that manifest in elevated ubiquitin processes that drive change quickly. This might be why you can't link bacteria to eukaryotes. The eukaryotic cells appears to be able to handle higher energies from the sun far better than the prokaryotes. Water is an electromagnetic repository for that energy. DHA has the ability to change solar radiation to a DC electric current in all plants and animals. This includes the eukaryotes. Pollack makes no claim on the origin of life.......but he gives us a far superior way to capture energy so we don't contravert the second law of thermodynamics. My one beef with Lane is that he holds Mitchell work in high regard. Ling undressed Mitchell because the chemiosmotic theory breaks the second law by an unreal margin.......Anything that breaks that specific law is a falsehood. The way Mitchell has us using protons is wrong. I do think he deserves credit for bringing protons to the table......but the mechanism he provided was simplistic and linear. Protons and electrons are the key in a cell designed to be far from equillibrium. Mithcell idea was born in an equillibrium biased scientific world. Albert Szent Georgyi and Erwin Schodinger were right about life because they looked to physics and not to biology because energy generation was the key. It manifests by way of semiconduction and quantum mechanisms at play. DHA gave the ability to cells to harness more quantum mechanisms because of their remarkable ability to be supreme antenna's for environmental radiation to store energy as a capacitor. Water extends that charge saving ability. This is why water is always found next to DHA in eukaryotes. http://www.ars.usda.gov/SP2UserFiles/person/4986/set4/Final%20DHA%202012.pdf When you read Jim Al Khalili book after Lane's papers, books, and layer that with Crawford's DHA work you begin to see a more clear picture of why the eukaryotic cells looks as they do and why bacteria and archea focused for 4 billion years on being Olympic athletes of biochemical pathways. You stay simple with biochemical lifestyle and you gain massive complexity using electrons and protons in quantum fashion. DHA O2 and eukaryotes all showed up at the same time.

Jack Kruse said...

Lane says clearly in Chapter 5 he favors Occam's razor viewpoint in looking at the data Peter. Let me ask you, what is Occam's Razor to say about the 39 steps of photosynthesis that are all quantized and far from anything that resembles the simpliest answer to explain data? My point is photosynthesis forms the entire food web on this planet. For Lane to assume a lot of what he did about LUCA without thinking about what Crawford and Khalili have published from his own country kind of surprised me. I think there is nothing in biology that follows Occam's razor. I believe humans believe this only because they have not thought about how all things work fundamentally. Where light hits atoms. That science is weird and far from equilibrium and resembles much of what life is capable of.

Jack Kruse said...

And Peter, Nick Lane's book in its opening mentioned protonicity. Proton conduction. I was hoping your proton series was headed to this video. You asked how Pollack and Ling tie to Lane. Here is the answer. https://www.youtube.com/watch?v=QufAlEqUZmU#t=153

Peter said...

Jack,

Good grief no, I'm more of an engineer that a mystic. The woman does not speak to me!

Peter

JohnN said...

For those interested Mae-Wan Ho's book can be downloaded here:
http://www.academia.edu/6167570/Living_Rainbow_H2O_by_Mae-Wan_Ho_World_Scientific



JohnN said...

Peter,
I, on the other hand, am quite open to consider mysticism as a shortcut to explain the not-yet explanable. Dark matter, string theory or black hole comes to mind.

Example: Lynn Margulis was once a heretic, staunchily defended her endosymbiosis theory for several decades before it is considered an established paradigm. Her support of Gaia hypothesis is clearly not founded on basic science as far as I know.
Or consider Fritjof Capra's classic The Tao of Physics that relates eastern mysticism to many notions of quantum mechanics.

On a different note: Gerald Pollack was an engineer (more credible?) before a biologist and I found his latest book on EZ Water very interesting. I suspect it will take another book or two before Pollack circle back to Gilbert Ling's AI hypothesis but he's already provided some hints.

John

raphi said...

@Peter
- "I still buy in to concepts of nano machines with rotors, pores and conformational changes most easily describable in classical terms. " ==> as do I. I don't really see the mechanical view being (entirely?) mutually exclusive to EZ water dynamics.
- the acetogenesis / methanogenesis pathways question is one I can't (yet) come down on either side of (again, this is where chemistry limits me). really interesting nonetheless.

@Peter/@Jack
- I watched the Mae-Wan Ho video presentation & have 2 big issues with it:
1) acupuncture is not hard to empirically test. it has been tested and has always failed to show an effect beyond mere placebo. she tried to use quantum physics arguments with lots of obfuscatory language to provide a mechanistic explanation of how it could work, revealing her foregone conclusion that it does work when it clearly doesn't.
2) i'm always highly skeptical of (& annoyed by) people who are more interested in 'saying what they have to say' at the expense of being understood. she did just that, in effect skirting the whole point of communicating clearly as to enable mutual scrutiny of ideas.

@Jack
- "The eukaryotic cells appears to be able to handle higher energies from the sun far better than the prokaryotes. Water is an electromagnetic repository for that energy. DHA has the ability to change solar radiation to a DC electric current in all plants and animals. This includes the eukaryotes. Pollack makes no claim on the origin of life.......but he gives us a far superior way to capture energy so we don't contravert the second law of thermodynamics." ==> that is a theory I can 'get behind' in terms of trying to learn the physics better to see what sense I can make of it. Fascinating stuff! :)

@JohN
- it's important not to confuse heretics with mysticism. The latter is won't get you any sympathy here & can never serve anything, as it 'explains' unfathomable complexity with even more unfathomable complexity.

Peter said...

JohnN, I have a post part written about my background. Tau of Physics was an early read as was Davies' "God and the New Physics", Fred Hoyle assorted writings, Chaitow's "The Acupuncture Treatment of Pain" alongside my BSc thesis on the substantia gelatinosa and Gate Theory of pain. Some ideas speak more plausibly than others. I built my first and admittedly only (knowingly) quantum device (a tunnel diode oscillator) in the early 70s.

Raphi, any device as small as an ATP synthase will be a quantum device. Get that small and QED butts in, sometimes more than others. Complex I conducts electrons by a mix of tunnelling and conduction. Acupuncture is pretty hard core. Naloxone blocks it nicely, conjoined circulation (between two goats if memory serves) cross transfers acupuncture analgesia from one to the other, steroids (which amongst many functions block phospholipase A, so no DHA release from neural membranes) also effectively block acupuncture. Acupuncture is like osteopathy. I recall crawling in to an osteopath's having had a wild day sailing and repeatedly capsizing a Fireball dinghy (great times). He crunched my spine. I walked out.

Do I believe all the stuff about realigning discs? Of course not. It's a rule of thumb for a process which works (if you don't fully prolapse a disc in the crunch!). Acupuncture is the same. It does something. I don't do all the ying and yang stuff, but it clearly does do something...

"2) i'm always highly skeptical of (& annoyed by) people who are more interested in 'saying what they have to say' at the expense of being understood. she did just that, in effect skirting the whole point of communicating clearly as to enable mutual scrutiny of ideas". People with correct ideas have a duty to communicate. Understandably. I gave up just after half way.

Peter

raphi said...

@Peter

Absolutely, electron transfers (reduction/oxidation) and ion channel function (for e.g.) have quantum mechanics at their heart. Re-reading what I wrote, that sentiment isn't clear actually - I didn't intend to present it as an either/or proposition.

Could it be that acupuncture is a particularly effective placebo? Can some placebos be more effective than others? David Colquhoun & Steve Novella make a convincing argument against acupuncture. I generally don't like Steve Novella, as he's a a bit of consensus-sheep. Nonetheless...http://www.dcscience.net/2013/05/30/acupuncture-is-a-theatrical-placebo-the-end-of-a-myth/

Jack Kruse said...

Peter,

You said, "Good grief no, I'm more of an engineer that a mystic. The woman does not speak to me!"

Check pg 227 of Lane. What did Nick say?
The more you learn the clearer it becomes that all the most interesting problems in physics are now in biology.

Sometimes you need to understand the mystic to view the problem from another perspective to solve it.

Jack

Jack Kruse said...

Raphi Accupuncture has been tested by Becker in the 1970's. NIH paid for it.

raphi said...

@Jack

I don't see why the funding source really matters, ultimately. I looked at acupuncture with an open mind and was even nearly convinced at some point that there was a very small but real effect. The more I read beyond those initial finding however, that tiny effect trends towards insignificance the more rigorous the study. Cumulatively, the better hypothesis seems to be that there is no effect beyond placebo (even a strong one, admittedly).

Either we do science or we fall for mysticism. Scientific advances do turn presents as the equivalent of magic into scientifically reality, granted. This does not change the fact that we need to approach any claim with the same standard of rigor. If not, then everyones pet theory gets a lower standard of evidence and no one benefits in the end.

Michael Frederik said...

"there is no effect beyond placebo"
Having read some of Ted Kaptchuk's work, I thought the same. But can what Peter describes above be placebo?
Or take homeopathy. Could there be any greater nonsense? Well, can't dismiss it according to Pollack. Talks about it here for 5 or 10 mins:
https://youtu.be/2edKFnVX5CE?t=59m0s
Sound like more nonsense to me, but I've been humbled too many times. I don't know.

Jack Kruse said...

Raphi where money comes from for a study is always germane. In fact it should be the first thing we look at even before we read the paper. My sensibilities are quite different from yours. My perspective is formed because of the what has happened to the literature. It is so abused it is close to useless and non functional for study and learning. My point is simple.......Read Nick Lane's new book. Chapter 5 to the bibliography, Nick is telegraphing to the world the answer is in the biophysics in the distance of the mosaic in the inner mitochondrial membrane and the distance and the magnetic and electric field landscape between the mito DNA and nuclear DNA. He has physics people in his lab now and is using math to measure things that biologist have no clue about. 1 angstrom different lowers quantum tunneling by a factor of ten. Do you know what this means for ATPase? It creates over one million times less ATP. Whether you believe Mitchell or Ling........that difference is massive and directly couples to ubiquitin rates and metabolic rates. Nick Lane is headed down the path of plenty. Peter likes Nick as I do. This book is telling every clinician and researcher the answer is in physics. These relationships all sit at the head of the table and the biochemical pathways are subservient to these hierarchical maneuvers. I been saying this.......a long time and now Nick is saying and writing it. I rather like that direction.

raphi said...

@Jack

Funding source is always germane but it can't speak louder than the actual data (assuming it's not fraudulent which is terribly difficult to figure out sometimes - sometimes not). I always highlight/make not of the funding & competing interests when I go over a paper, so I think we agree on its importance. Is the particular abuse your referring to concerning acupuncture studies? I'm open to changing my mind but the David Colquhoun link I posted above makes a convincing case. Feel free to link to something that'll overturn that.

I am slowly getting through Thomas Seyfried's tome on Cancer as a metabolic disorder for my master's thesis. Everything you mention about the physics seems relevant to Seyfried's work but mostly on an intuitive level for me - I've yet to acquire a better understanding to actual put that intuition to the test.

You may have convinced me - I'll make an effort to read Nick Lane's new book in parallel with Seyfried's and see if I can form a more cohesive picture and/or put my finger on contradicting points. I like that direction too Jack, although I'm careful as can be about not bringing extra pseudoscientific baggage** with me down the path of biophysics. What is poorly understood is easily abused and the easiest people to fool are ourselves.

** homeopathy certainly, acupuncture probably

George Henderson said...

Just a few more polyprenyls for consideration -

http://en.wikipedia.org/wiki/Dolichol

Peter said...

Thanks George, interesting

Peter

JohnN said...

'saying what they have to say' at the expense of being understood.
Nicely put. That's why I recommended a short read of her idea.
Not all lecturers are good conveyors of their idea, unfortunately.