From nitrogen to oxygen and everything in between.

Is it possible that our metabolic processes are multiple tiered, with oxygen dependent processes being only the most recent/top level process?

What mechanism in the selective process would allow us to completely abandon the nitrogen breathing/dependent process?

Do brains work by balancing different metabolic processes against each other?

Perhaps not nitrogen fixing, but a balanced aerobic and anaerobic process?

How much (if any behavior) is driven by this anaerobic/aerobic balance?

One step beyond a ribosome: The ancient anaerobic core – Interesting, so the supposition may actually be correct. Looks like the genetic heritage from Last Universal Common Ancestor (LUCA) is still intact even among aerobic organisms.

The prokaryote ancestor did possess, however, an Mrp-type H+/Na+ antiporter complex, capable of transducing geochemical pH gradients into biologically more stable Na+-gradients.

Okay, this is one of the questions I’ve had stuck in my head for awhile, whether hydrogen could sit on one side of the metabolic pump akin to lithium. Apparently so!

Animal plasma membrane energization by chemiosmotic H+ V-ATPases – Whoa! So the NKA pump is just a convenient steady state dependent on external conditions.

ATP synthase: Evolution, energetics, and membrane interactions – LUCA and the commonality of energy mechanics across life. Life has an anaerobic base.

New vocabulary – “Anoxygenic Photosynthesis”. Fascinating!

Animal plasma membrane energization by chemiosmotic H+ V-ATPases – I’ve never seen anything like this in any of the biology texts I’ve been exposed to up until this point.

Targeting molecular hydrogen to mitochondria: Barriers and gateways – Am I blanking so bad that I completely missed the hydrogen interactions inside of mitochondria?

So this is off topic and my brain is wandering a bit but… H+ seems like it would be the most perfect anti-oxidant ever, especially considering the “waste” product. My brain is telling me that I need to take another look at AQP mechanics. Considering the metabolic effects in mito, are we seriously looking at hydrogen for resolving neurodegenerative conditions right now? Maybe even diabetes or lipid synthesis as well?

Looking Back to the Future of Mitochondrial Research

It should also be mentioned that mitochondria play a key role in degenerative diseases, particularly muscular dystrophies and neurodegenerative conditions ranging from Parkinson’s to Alzheimer diseases, amyotrophic lateral sclerosis, multiple sclerosis; and in organ ischemia-reperfusion injury.

To be fair, this is a more recent understanding, but yes and I guess this is where I drew the inference from.

Remarkably, knockouts of mitochondrial pathways that are presumed to be essential, including complex I, grew relatively well at low oxygen (Jain et al., 2020). This approach is leading to the discovery of hundreds of genes linked to oxygen homeostasis, and there is more. Hypoxia has recently been shown to induce matrix acidification with release of Ca2+ from calcium phosphate precipitates, increased free [Ca2+] and matrix influx of Na+ on the Na+/Ca2+ exchanger (Hernansanz-Agustín et al., 2020).

Na+ interaction with phospholipids then reduced inner membrane fluidity, selectively decreasing mobility of free ubiquinone between complex II and III but not inside supercomplexes, thus leading to increased superoxide production at complex III, a novel control mechanism of redox signaling that may have profound consequences for cellular metabolism (Hernansanz-Agustín et al., 2020).

It always freaks me out when I make a wild ass guess then read it stated more explicitly in papers. I feel like I need to do a better job with opposing evidence but not even sure where to look.

The key role of the H+ V-ATPase in acid-base balance and Na+ transport processes in frog skin – A bit random, but provides some evidence to the mechanics of cellular pH management across ethological boundaries.

The metabolic network of the last bacterial common ancestor – Okay, back to the beginning.

The most important difference between anaerobes and aerobes is related to energy; anaerobic pathways such as fermentation, sulfate reduction, acetogenesis, and methanogenesis yield only a fraction of the energy when compared to aerobic pathways, but this is compensated by the circumstance that the synthesis of biomass costs 13 times more energy per cell in the presence of O2 than under anoxic conditions.

Wow!

That is, the absence of O2 offers energetic benefits of the same magnitude as the presence of oxygen does. Although the advent of O2 expanded routes for secondary metabolism, allowed novel O2-dependent steps in existing biosynthetic pathways, and allowed the evolution of new heterotrophic lifestyles by enabling the oxidation of unfermentable substrates, the advent of O2 did not alter the nature of life’s basic building blocks nor did it redesign their biosynthetic pathways.

And that was a big part of the question.

These genes are nearly universal and are among the most vertically inherited genes in prokaryotes (Table 1). These 146 families were rechecked manually with regards to functional annotation (Supplementary Data 3) to provide a list of gene functions that trace to LBCA. Around half of those families are involved in information processing, protein synthesis, or other structural functions (Table 1), and the other half can be mapped to at least one metabolic reaction in KEGG, the Kyoto Encyclopedia of Genes and Genomes (even if often also involved in information processing, e.g., the transfer RNA (tRNA) charging category), thus providing insights into LBCA’s physiology and lifestyle.

Man, how the hell did Chucky D guess this by looking at some damn birds? Amazing.

The compounds missing are the charged tRNAs for Lys, Met, Ile, Pro, Asn, Gly, and Gln and two cofactors (thiamine diphosphate and pyridoxal 5-phosphate). Using a network expansion algorithm48, adding all reactions encoded by non-LBCA genes to the network, and then sequentially and gradually removing them until the production of all universal metabolites was possible with the minimal set of reactions (see “Methods”), we found that the addition of only nine genes—seven aminoacyl tRNA synthetases (aaRS), ADP: thiamine diphosphate phosphotransferase and d-ribulose 5-phosphate, d-glyceraldehyde 3-phosphate pyridoxal 5′-phosphate-lyase—completes the network to generate all 57 universal compounds (Fig. 1 and Supplementary Data 4). It is likely that ancestors of the two classes of aaRS enzymes acted promiscuously in charging tRNA in LBCA49.

LMAO. The core metabolic mechanics have been barely changed for billions of years. I have a feeling that “more alike than different” is going to become a recurring future meme.

Energy at Origins: Favorable Thermodynamics of Biosynthetic Reactions in the Last Universal Common Ancestor (LUCA) – Last touch before going back up the chain.

Organisms that use the acetyl-CoA pathway still inhabit H2-producing geochemical systems, habitats that existed on the early Earth.

Oh man. Like 99% of behavior lives in this pathway.

Though the remaining chemical reactions of the core do not occur in all genomes, as auxotrophies arise recurrently in evolution, they are universal at the level of primary production, the process that has fueled all ecosystems from origins to today.

Okay, so aerobic processes are bolted on top of primary anaerobic processes, with aerobic processes largely being an adaptation to the oxygen explosion. Smell test for all of this… the size of animals/plants would be relative to amount of oxygen in the atmosphere. This would assert that back when dinosaurs and jesus were kicking it, atmospheric O2 was quite a bit higher. We should see a consistent tie between size of organisms and atmospheric O2.

An interesting parallel is that ice ages probably represent hypoxic events. What if mega-fauna extinctions are the result of this metabolic deficiency rather than other events? Could the Dryas extinction for instance been an artifact of drops in atmospheric O2 due to glacial advance? Could the difference between the survival of Sapiens vs. Neanderthal not have been about competition, but Neanderthal bodies not being able to shrink as fast as Sapiens did?

Okay, need to take another look at ammonia fixing processes next. Early atmosphere was mostly ammonia and it looks like the nitrogen in our atmosphere is mostly an artifact of the hydrogen fixing processes of early life. There’s probably some significant insight to be gleaned from the ammonia/urea fixing process in cells.

More crazy speculation, but did the ice giants/triton generate massive amounts of “life” (or at least it’s precursors) before earth had fully formed?

Absorption wavelength along chromophore low-barrier hydrogen bonds

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