Thursday, March 31, 2022

H2O2 too?

There are many hypotheses for the ‘crucial ingredient’ in the origin of life. Adding to this list is hydrogen peroxide, H2O2. That’s the suggestion of Rowena Ball and John Brindley in a review article with an intriguing title: “The Power Without the Glory: Multiple Roles of Hydrogen Peroxide in Mediating the Origin of Life” (Astrobiology 2019, 19, 675-684). It is clearly labeled as a Hypothesis article, and the authors carefully state that “this discussion is purposely (and necessarily) speculative… to stimulate further ideas concerning possible feedbacks between and evolving biomolecular system and its energetic medium, and how these interactions themselves may have shaped emergent life.”

 

H2O2 has long been cast as a villain. You’ve probably heard the standard joke of someone who walks into a bar, asks for H-2-O, gets a glass of clear liquid, drinks it up, and declares it refreshing. On hearing this another patron asks for H-2-O-too, gets a class of clear liquid, drinks it up, and dies! We think of H2O2 as toxic. We caution our students in chemistry lab to be careful when handling it because of its reactivity. The two are related. Because of its anomalously weak O–O (single) covalent bond, H2O2 is considered a ‘high-energy’ molecule and thus reacts favorably in exothermic reactions. It is part of the family of ‘Reactive Oxygen Species’ known in biology and the behemoth cosmetics industry as something that ‘causes damage’ broadly speaking.

 

Five years prior to this article, Ball and Brindley had examined the thiosulfate hydrogen peroxide (THP) redox oscillator. Thiosulfate and H2O2 react heartily and quickly according to the chemical equation:

 


Ball and Brindley argue that the THP oscillator provides a power source, i.e., its exothermic reaction releases energy that can potentially power anabolic reactions and build molecules required for biomass. This “chemiosmotic coupling”, they argue, provides “a viable alternative (or complementary) alternative to… proton gradients across alkaline hydrothermal vents” as proposed by Nick Lane and others. Ball and Brindley also claim that it “improves ribozyme activity [and] provides a possible resolution of the replication versus ribozyme activity paradox”. I haven’t read their cited paper, but I think their argument is that varying pH allows another route between functionally folded ribozymes acting as replicases and the need to also unfold as a template for replication.

 

One intriguing part of their paper is that their previous simulations with the THP oscillator lead to an unexpected probability distribution. Not having read the cited work, I don’t know how it works. But in any case, while we often observe the perturbation of a Gaussian distribution into a Maxwell-Boltzmann distribution (left-heavy with a long tail on the right) that all my students should recognize, the THP oscillator, under the appropriate non-equilibrium conditions, leads to a right-heavy perturbation. Here’s their figure showing the three cases: Gaussian, Maxwell-Boltzmann, and their New Distribution.

 


This result is potentially interesting but, without seeing how their new distribution is perturbed as other environmental conditions change, it’d difficult to assess its importance as a driving force for molecular assembly that builds order even while seeming entropically unfavorable. Nevertheless, it is intriguing. The authors tantalizing suggest that “characterizing this distribution in explicit form could effectively give us a fundamental equation of life which may provide useful guidance in designing molecular experiments: they should be messy… but not too messy.”

 

As to why all of life seems to use the same machinery (genetics and metabolism), they argue that the rise of catalase enzymes to effectively remove H2O2 cuts off the possibility for new life to begin powered by H2O2. In effect, this is “pulling up the ladder” after you’ve climbed up the tree so no one else can follow suit. They characterize evolution as “the burning of a succession of small bridges: the results of a transformational evolutionary step usually destroy the preconditions for its own occurrence.”

 

Personally, I’m skeptical that H2O2 plays such an important role. I can see how, if formed, it can be an energy source. But it’s highly unlikely to be a useful one that leads to a series of ‘forced trajectories’. Rather, I expect H2O2 in a prebiotic milieu would be indiscriminate in its reactivity. It’s akin to striking a match and burning your fuel directly, blowing off the released energy as heat, and going directly to low-energy ‘waste’ molecules, rather than the tortuous and intricate path used by life in its dance of anabolism and catabolism.

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