CHEMISTRY:

SUMMARY: The time required for biochemical evolution, regarding very slow reactions in a warm environment, is far less than commonly presumed, and primitive catalytic effects can increase with cooling temperatures. These observations plausibly explain how life may have established itself and evolved on Earth.

How did life become established on Earth? Scientists have developed a number of relevant hypotheses, e.g. that a comet impact may have catalyzed amino acid synthesis, the voids within ice crystals may have served as the first "living cell", and biomolecules may spontaneously organize themselves within a cell when the interior is crowded.

Such hypotheses answer questions of how the molecular constituents of life may have arisen, how self-replicating molecules may have begun to propagate themselves, and how cells developed the complexity necessary for advanced life. They do not convincingly answer the fundamental question of how modern life and its requisite biomolecules (e.g. enzymes) evolved relatively quickly on Earth.

The establishment of enzymes: A mystery.

Enzymes are critical to life as we know it. These biomolecules greatly speed up the chemical reactions required for life, e.g. those relevant to intracellular energy production.

How much time would be required to execute a biochemical reaction without enzymes? An extreme example is uroporphyrinogen decarboxylation, a step in heme protein synthesis (e.g. proteins for oxygen transport), which has a half-life of 2.3 billion years at 25°C.

In other words, half of the reactants are converted to products after more than 2 billion years. This is obviously a very slow reaction.

It's clear that such life-enabling reactions didn't "struggle along" at low temperatures, necessitating millions or billions of years to synthesize a few molecules, until enzymes gradually evolved over time; Earth is far younger than the time required for that to happen. Furthermore, life is thought to have established itself within the first 25% of Earth's history.

Is there some physical phenomenon that greatly accelerated the evolution of primordial biochemistry? If one is to propose such a phenomenon, it must plausibly explain how very slow biochemical reactions may have been accelerated, thereby establishing themselves on Earth and eventually developing into life as we know it today.

Richard Wolfenden (University of North Carolina Chapel Hill, United States) and coworkers point out that very slow reactions are greatly accelerated by the addition of heat. This simple yet underappreciated observation convincingly explains the relatively rapid development of primordial biochemistry on early Earth.

An underappreciated fundamental principle.

If you took a general or physical chemistry laboratory course at a university, at some point you probably performed the following experiment. You were instructed to determine the rate of a chemical reaction, at room temperature, that proceeds too slowly to directly measure.

With the knowledge that chemical reactions proceed faster with increasing temperature, you heated up your chemical solution. After determining the reaction rates at several elevated temperatures, you used an Arrhenius plot to extrapolate the theoretical reaction rate at room temperature.

This exercise is useful for illustrating the effect of temperature on chemical reactions. On the other hand, scientists generally don't appreciate the tremendous acceleration of many biologically-relevant reactions by heating to near the boiling point of water.

Consider the previously mentioned uroporphyrinogen decarboxylation reaction, which takes billions of years to complete at 25°C without an enzyme. Heating to 100°C reduces the half-life to 600 years.

Another example is fumarate hydration, a biochemical reaction important to intracellular energy synthesis. The half-life of this reaction, in the absence of an enzyme, is 700,000 years at 25°C; at 100°C, the half-life is only 10 years.

Wolfenden and coworkers have gathered experimental data on many such biochemical reactions. A pronounced trend in this data is that the slowest reactions increase most quickly with increasing temperature, essentially "leveling the playing field" of biochemical reactions.

How is this relevant to modern life? Biochemical evidence suggests that modern (common) life derived from microbes that thrive at high temperatures; such microbes are still alive today.

The reaction acceleration principles previously discussed supports such microbial evolution hypotheses. They also plausibly explain how primordial biochemistry may have originated relatively rapidly on a warm Earth.

Primitive biochemical reactions wouldn't have taken nearly as long on a warm planet as is commonly presumed. This in turn greatly reduces the length of time required for biochemical evolution.

Such reaction times, in years, are clearly still fairly slow. However, a simple catalyst (e.g. a metal ion) could presumably speed up reactions considerably from these more reasonable starting points.

How might life have evolved at lower temperatures on a subsequently cooling Earth? This is discussed next.

Life at lower temperatures.

A reaction that requires one million of years to complete at 37°C isn't plausibly favored from an evolutionary standpoint, even if a catalyst increases the rate by a factor of ten million (i.e. to 37 days). This leaves the question as to how cells developed the ability to function at such (relatively) low temperatures, after life was established at elevated temperatures.

A concept that may explain this question can again be found in general and physical chemistry. Whether or not a chemical reaction is thermodynamically favored (i.e. whether or not it can in principle proceed) is a function of the change in enthalpy (heat) and entropy (disorder) of the reaction.

A catalyst, e.g. a substance that facilitates a chemical reaction, must either reduce the enthalpy change (release more heat) or increase the entropy change (induce more disorder) of a chemical reaction's energy of activation. Which type of change is thermodynamically favored with reduced temperatures?

Wolfenden and coworkers plotted the rate enhancement of a generic chemical reaction by two catalysts, one that functions entirely by reducing enthalpy, and another that functions entirely by increasing entropy. They found that the former, not the latter, automatically increases reaction rates with decreasing temperature.

This suggests that primitive biocatalysts could have functioned more effectively in a cooling world by manipulating the enthalpy of their associated biochemical reactions. The scientists set out to test the plausibility of this hypothesis for the development of modern life.

They examined a number of biochemical reactions, all of which are executed in living cells with a nonenzymatic catalyst (e.g. a metal ion, such as Cs⁴⁺ in phosphate ester hydrolysis). They investigated the temperature dependency of each, and whether the catalysts act by reducing enthalpy or increasing entropy.

The effect of reducing enthalpy was favorable, and that of increasing entropy was unfavorable, in every case. Furthermore, many known enzymes function by reducing enthalpy, bridging the divide between simple and enzymatic catalysis.

Implications.

Wolfenden and coworkers propose that modern enzymes, more specifically their dependency upon reduced enthalpy change of activation, evolved into what they are today specifically due to their striking dependence upon temperature. Primitive catalysts were sufficient to get life started in a warm world, and more advanced catalysts (e.g. enzymes) evolved to take advantage of basic physical chemistry relevant to a cooling world.

There are clearly other important factors relevant to biochemical evolution not discussed herein, e.g. the development of specificity, referring to the observation that only a small number of enzymes can contribute to a specific biochemical reaction pathway in a complex environment (i.e. a cell) if there's to be some semblance of order and control. Nevertheless, basic principles from physical chemistry offer a plausible explanation for how the chemistry of life developed on early Earth and advanced to the state observed today.

NOTE: The scientists' research was funded by the National Institutes of Health.

Stockbridge, R. B., Lewis Jr., C. A., Yuan, Y., & Wolfenden, R. (2010). Impact of temperature on the time required for the establishment of primordial biochemistry, and for the evolution of enzymes Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.1013647107