Friday, August 10, 2012

We are not alone

Obviously anyone with even a basic interest in origin of life questions will be watching the progress of Curiosity on Mars. Those of us who buy in to the serpentine and alkaline hydothermal vents concept will be interested in whether the crustal chemistry of Mars is olivine based and whether major water bodies were even present. Or equally, whether a semblance of white non-smokers might be present when acidic ground-water interacts with olivine, without needing an ocean and vents... An interesting time for testing hypotheses about whether there is life "out there", in our own back yard...

EDIT: A quick google shows olivine, serpentine and methane plumes are all present on Mars. The methane could easily be abiotic in origin, the question is whether it actually is or not...

On the more down to Earth front, if anyone thinks my basic ideas about the ratio of FADH2 based input vs NADH input to the ETC determining superoxide production are not totally incomprehensible, we are definitely not alone. I had a very nice email from Dr Speijer in Amsterdam, a fellow thinker along these lines. He has come to exactly the same conclusions and published an hypothesis paper in Bioessays back in 2011. The first section is just excellent. We may diverge in interpretation (but not FADH2:NADH ratios) very slightly late in the essay on PUFA, but it really is full of very good thinking and an excellent paper.

His ideas about peroxisomes (a very early eukaryotic invention) of course addresses that age old question of "Who's (macroscopic) fat is it anyway?", the answer being that the gut bacteria own it. On the sub cellular front, fat is primarily made in cytoplasm but at the behest of the mitochondria, only secondarily in peroxisomes and, as peroxisomes are probably a response to deal with overly long (ie excessively high FADH2 generating) fatty acids, the answer would seem to be mitochondria order fatty acid production, they own them and they have their own agenda for them. It's a sort of intracellular parallel the the fiaf series on gut bacteria and adipocytes. Very interesting concept.

If mitochondria own fatty acids I would expect them to enjoy burning fatty acids. Whatever the generation of controlled superoxide is, it's what keeps mitochondria happy. Then there is the brain to think about, its avoidance of fatty acids, it's love of ketones for an occasional fling and its very probable long term love affair with lactic acid. All based on FADH2 to NADH ratios of course.

There's a lot to post about. Back to the Protons series next (I think).

Peter

11 comments:

Edward J. Edmonds said...

“If mitochondria own fatty acids I would expect them to enjoy burning fatty acids. Whatever the generation of controlled superoxide is, it's what keeps mitochondria happy. Then there is the brain to think about, its avoidance of fatty acids, it's love of ketones for an occasional fling and its very probable long term love affair with lactic acid. All based on FADH2 to NADH ratios of course.”

This is getting good. And you’re raising some questions I’ve been asking for a long time.

Just some thinking my angle might not make sense :) But when we are looking at things at a very fundamental level some other important questions come up.

Lactic acid… One of the problems I’ve been wrestling with is D-fructose and it’s isomers in metabolic pathways. I’m looking for a way to explain the presence of GLUT5 transporters in the body. From what I’ve read it seems like fructose metabolism is primitive. GLUT5 transporters presence in what seems like high energy organs is intriguing. I’ve not read any satisfying explanation for this. GLUT5 expression seems to be controlled by the cerebellum (http://goo.gl/9AtlI). Fructose seems to be converted to lactate in the brain (http://goo.gl/jxJ8b). Interesting (http://goo.gl/pGxdm).

With all the metabolic machinery in place to eliminate/use (depending on the perspective) one can’t help but ask at what point was the primitive environment filled with enough fructose to trigger these metabolic adaptations. Which came first the fruit or the metabolic pathway? Does fructose interfere with oxygen metabolism, if it does, is it harmful? Because I view the handling of oxygen or the lack thereof as something important.

I’ve always viewed mitochondria as an adaptation to handle extra atmospheric oxygen whether they were a symbiotic development or of eukaryotic origin (http://goo.gl/fgngw, seems neater). So the idea that fat would be the preferred fuel is cut and dry for most the organism. But fatty acids would have also had to be present in the early environment for the development of that mechanism. So we then would have to ask where did all the free fatty acids come from.

The preference for glucose and ketones in the brain seems straight forward in that the brain is made of fat (insulation) which tunnel higher energy things glucose/ketones (electricity if you will, bad analogy) when the brain becomes compromised i.e. changes in composition for whatever reason it would seem straight forward that glucose metabolism would become compromised/leaky and the thing would malfunction.

I’m coming to view the brain and “its” body in a rather selfish way… it seems like the body has plenty of mechanisms to make sure that it always has glucose or ketones. It really makes the brain/body very self-sufficient and more likely to survive if the source of fuel (some better than others) can vary yet continue to keep the brain energized. We can think about this in an evolutionary perspective. If we use are imagination we seem like one giant cell, all our sensory facilities, everything is for moving and navigating the brain through the environment like we are one giant single celled organism. Looking at the different body parts and organs some seems to prefer different fuel sources leading me to think the entire body is one giant symbiotic relationship. Our taste buds and drive for certain foods leading us to eat in a way to supply each component with its preferred fuel.

George Henderson said...

Electricity is not a bad analogy.
The car's onboard computer cannot run on petrol, but petrol supplies the energy to generate the electricity.
I see metabolism as a hybrid car, in which fat = electricity. You can load this from the mains or generate it from gas (carbs) as you drive on it. But this ignores the non-motor electrics/brain analogy, so back to the drawing board.

I'm leaning towards thinking fructose is favoured because of its all-or nothing presence in nature.
Grab it while it lasts; glucose is probably endogenous, fructose is always exogenous, so pull it in first.

The brain burns fat slowly. Probably most comes from converted glucose.

"In the rat the half life of depot lipid is about 8 days; in the liver of the rat, the fatty acids have a half-life of about 2 days; in the brain, 10 to 15 days."

O Numnos said...

At the risk of sounding a bit dim I've been trying to get ahead (less behind?) on the subject of superoxide and IR.

This has lead me to Acontiase and it's inhibition by superoxide and subsequent effects on mitochondrial respiration - sp citrate/pyruvate/malate - is this the likely connection (or bollox?)

Peter said...

Edward, Yes, I think very much along those lines. I can't recall where I heard that glucose might be a derivative and fructose was the primary carbohydrate, but the idea is out there and probably correct. No time to follow your links before dealing with the chickens, chicks and our ex-batt with healing broken leg (The morning and evening chicken shuffle as we don't have enough coops for the needed functions) but here are two links Dr Speijer fwded to me.

http://www.nature.com/nature/journal/v487/n7408/full/487435a.html

http://www.nature.com/nature/journal/v487/n7408/full/nature11314.html

George. I roughed out a post comparing fatty acids to a base load nuclear power station like my local Sizewell B vs glucose being more comparable to Gt Yarmouth's North Sea gas fired unit which seems to switch on and off to boil a kettle.

I still quite like the comparison...

O Numnos, aconitase looks to be a very interesting enzyme. I'm still thinking about general implications rather that very specific steps but the iron sulphur cluster does seem fundamentally different from the FeS clusters so ubiquitous in metabolism. Definitely somewhere to look. I really love FeS clusters. How common will iron sulphur compounds turn out to be on Mars?

Peter

Stan (Heretic) said...

Iron is very common over there, that's why the planet looks red. Sulfur is also common, since oxygen is depleted and lost due to low gravity, then sulfur generally takes up its role in the lithosphere and may in fact dominate but need not necessarily be very common on the surface since it is very reactive and quite volatile.

Re: fructose in the primary environment.

How come if that is one of the most reactive sugars? A more likely choice is probably cellullose as the primary ubiquitious substrate

Re: Edwards ideas on mitochondria's origin

It seem that fatty acids are close analogues to hydrocarbons, thus mitochondria could have originated as the free bacteria feeding off hydrocarbons seeping out from the depths (plenty of them in the environmanet, even now), oxidising them using sulfur first, then oxygen in the later epochs. Then when the amount of hydrocarbons available in the environment diminished, they became symbiotic to yeasts type of microorganisms , learned to live inside their cellullar structures and process fats instead of hydrocarbons. (P.S. thanks for the article link on F1,6BP and anticonvulsant - there is a very interesting connection mentioned between glucose metabolism in general, and epilepsy!)

Regards,
Heretic

blogblog said...

I've come to the conslusion that we are little more than life support sstems for our gut microbiota. They control what we eat.

Kindke said...

blogblog,

Yes that is exactly how I view it. Just like how multiculturalism will never work, because humans instinctively band together in "tribes", these tribes work together to defend their land ( and women! ) from other tribes.

Humans criteria for banding together is based on their "strain", just like bacteria.

The same behavior is evident in gut flora, similar strains of bacteria band together and work together. Our colon is "their" land, and they will defend it from other tribes ( other bacteria strains ).

If hostile aliens suddenly landed on mars and started invading earth, then I would expect all humans to band together to defend planet earth "our land". ( or wait...is that too naive of me? lawl )

The same phenomenon that exists on the microscopic scale is ultimately exhibited over to the macroscopic scale. A perfect example of how the universe is fractal.

George Henderson said...

Do microbes then display altruism, like animals or communal insects?
Is there even altruism of sorts in the sum of the interactions between related viruses in a host?

George Henderson said...

The beri beri weight loss diet; I've posted the thiamine hypothesis here.
http://hopefulgeranium.blogspot.co.nz/2012/08/the-role-of-vitamin-fortification-in.html

That should put the cat among the pigeons.

blogblog said...

@George Hendersen,
in reality most beer is an extremely poor source of thiamine (<0.05mg/L) because the yeast is removed before bottling. You would need to drink about 25 litres a day just to met the RDI.

George Henderson said...

There's carbohydrate in beer too, maltose which is a glucose dimer.

Lager style beers were found to contain significantly (p < 0.001) less thiamin than other tested styles of beers (lager, 35.7 μg/L; ale, 88.3 μg/L; stout/porters, 104.4 μg/L; wheat beers, 130.7 μg/L), which may be due to the raw material and extensive processing that occurs for this style. There was no statistical difference (p = 0.608) between the riboflavin content of each beer style. Furthermore, wines and ciders contain less thiamin and riboflavin than beer.
Australian beers; http://www.ncbi.nlm.nih.gov/pubmed/22087742

And spirits etc. would contain zero.
Of course a beer drinking alcoholic can easily drink 4 or 5 liters a night. A source, but not such a great one then.