Discussions and reflections on science and life

Dang are they weird…but what would we do without them?

with 3 comments

So, Val asked in the comments:

As someone with a sweet tooth for speculative biology, I can’t help inquiring as to the materials which you refer in this passage:
“although there have been some theories about alternate high yield ATP production pathways or schemata of power management”

Could you please point me towards sources where I can find out more about said hypothetical pathways and power management schemata?

And since it is an interesting question, and since I should be making a post today anyway, and since I made a mistake in that initial statement that needs to be fixed, I thought I would go ahead and take a shot at answering it out here on the frontpage.

Firstly, I need to admit that I mistyped that first part and clarify a bit. I am not personally aware of any proposed higher yield pathways (although I would not be surprised if they were out there, but that level of biochem is a region to which I venture only rarely). When we talk about the yield of a metabolic pathway we generally express it in terms of the amount of product per cycle or the amount of product per amount of reactant. What I meant to say was that there are theories concerning how to increase the amount of product per time. The distinction may seem academic, but a faster pathway generating less ATP per cycle is technically lower yield than a slow pathway generating more ATP per cycle, even if the faster one produces more net ATP in the same amount of time. So what I meant to say was that there were “theories about alternate high rate ATP production pathways“. I hope that clears things up.

For those of you who don’t know, our (and other aerobic metabolizers) primary method of ATP production is a process called oxidative phosphorylation, which is dependent on our mitochondria. It is a low rate, high yield process resulting in ~32 mol ATP per 1 mol glucose. The primary method of ATP production in anaerobes is fermentation. It is a high rate, low yield process resulting in 2 mol ATP per 1 mol glucose. This trade off between yield and rate seems to be a necessary physical constant due to thermodynamic principles. All eukaryotic, multicellular life is dependent on aerobic metabolism. It’s just good evolutionary sense, as detailed in “Cooperation and Competition in the Evolution of ATP Producing Pathways” (Pfieffer, et al. 2001). But does it have to be? The answer is: probably not.

In fact, depending on what your definition of eukaryotic, multi-cellular life, then the answer is a firm “no”. Most cancers do not make use of oxidative phosphorylation even in an aerobic environment. This phenomenon, known as the Warburg effect, hinges on two factors: (1) as Pfieffer, et al. show, high rate low yield ATP producing pathways are selected for in cases of competition for resources (and the cancer can be seen as an independently evolving, parasitic entity in competition with its host); and (2) the intermediates generated by glucose metabolism are requisites for growth, thus proliferating eukaryotic cells benefit more from a higher concentration of glycolytic intermediates than they do from a higher concentration of ATP. A good review of the history and current research on the Warburg effect is “Cancer metabolism: the Warburg effect today” (Ferreira 2010).

If we take the Warburg effect as a real-life, proof of concept, the speculation can extend down to main paths: (1) eukaryotic cells do not possess a pressure for high yields of ATP under all conditions; and/or (2) a sufficiently high rate in the appropriate environment could overcome the pressure towards high yields.

Towards the first point we can imagine a form of eukaryotic life that goes through metamorphic phases, for instance a proliferative phase that requires high metabolic intermediates and low ATP before metamorphosing to an active phase at which point ‘banked’ ATP could be used in one great sprint to breed and die. Something very similar occurs in the male fish of the family Cetomimidae which take up energy in a larval phase and expend it in a brief mature phase (Johnson, et al. 2009). Of course in our putative life form the immature phase would be in complete torpor, again something we see in the metabolism of certain existent creatures like hummingbirds that go through cycles of torpor and energy expenditure. An exploration of this concept can be found in the speculative fiction novel Blindsight, by Peter Watts.

The second path is a bit more open. Quantum tunneling has been shown to increase the rate of biochemical reactions by over 100 fold, as yet unknown enzymatic activity could boost reaction rate through conventional means, and once again environment has a definite role to play in exactly what constitutes a critical ratio of rate/yield. It has been shown that one of the consequences of mitochondrial variation across species is that the rate vs. yield of oxidative phosphorylation varies slightly, and in no species is it set up for highest possible yield (Pfeiffer, et al. 2001).

The important thing to remember here is that evolution is an environmentally-dependent and path-dependent process. Just because it has accomplished a specific end in a certain way, does not mean that was the only solution (or even the best one).

Sources & Further Reading

Written by Caudoviral

03/09/2011 at 18:54

Posted in Biology

Tagged with , ,

3 Responses

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  1. Thanks :)

    “Quantum tunneling has been shown to increase the rate of biochemical reactions by over 100 fold”

    Correct me if I’m wrong, but isn’t tunneling already accounted for in conventional reaction rates (IIRC the 100-fold figure comes from deuteration experiments, where rates of some reactions dropped by that value due to deuterium being introduced) ?


    03/10/2011 at 03:28

    • If I correctly understand what you mean by “conventional reaction rates”, then the answer is yes (although as far as I know you might be in error about how the figure was produced, everything I have read has derived these figures from the comparison of classically derived expected reaction rates vs. experimentally verified actual reaction rates). But I think you have missed my point.

      I am not saying that we could somehow mystically induce greater quantum tunneling at physiological conditions in the metabolism of common organisms and increase reaction rates. Those are already accounted for. The acknowledgement of quantum tunneling effect and its mention next to classical enzymatic effects was to show two axes of variation in these metabolic paths: the “over the barrier” classical requirement and the “through the barrier” quantum requirement. And these two requirements do not vary in proportion to one another as environment changes. For instance, tunneling reaction rates can be entirely temperature independent, a thermodynamic impossibility for classical reaction rates. Organic chem reactions have been accomplished through carbon tunneling at ~10K, a temperature at which the “over the barrier” classical requirement would render the chances of the reaction occurring effectively 0. Our conventional predictive equations work well in conventional circumstances, but are still are lagging behind observed phenomena. See “Chemical Reactions Involving Quantum Tunneling” (McMahon 2003).

      Essentially, we are capable of accomplishing reactions that would be considered impossible by classical chemistry, and this must of necessity cause us to widen our gaze in speculative biochemistry and in the study of extremophiles. Tardigrades and other polyextremophiles can survive in a number of environments that would play havoc with conventional chemistry, whatever biochemical reactions are occurring in those environments are not exactly at standard temperature and pressure.


      03/10/2011 at 12:11

      • Ah, okay, now I see.

        Hm… I distinctly recall the “100” figure being somehow connected with proton tunneling in enzymes and its shutdown upon deuterium introduction… Guess I’ll try to track down that paper.


        03/12/2011 at 15:32

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