June 21, 2004 | David F. Coppedge

Mystery of the Left-Handed Proteins: Solved?

Some molecules come in left- and right-handed forms that are mirror images of each other.  All biological proteins are composed of only left-handed amino acids.  How this could have come about in a primordial soup has long been a puzzle to origin-of-life researchers, since both L (levo, left-handed) and D (dextro, right-handed) forms react indiscriminately.  (That biology is single-handed was first noted in the 1800s by Louis Pasteur.)  For those familiar with the problem (see online book for background information), a press release from Imperial College, London is sure to draw attention.  Its optimistic title proclaims, “How left-handed amino acids got ahead: a demonstration of the evolution of biological homochirality in the lab.
    It refers to a paper in the German journal Angewandte Chemie1 by Blackmond et al., who begin their paper with a review of research on this mystery.  (Terms are defined in brackets.)

The origin of homochirality [one-handedness] has intrigued scientists ever since the biological importance of L-amino acids and D-sugars was first recognized.  Although a theoretical basis for the evolution of high optical activity [purity of one hand rotates polarized light, thus optical activity] from a minute initial imbalance of enantiomers [each hand is an enantiomer of the other hand] was suggested more than half a century ago, experimental proof of such a concept eluded scientists until a remarkable report by Soai and co-workers in 1995.  The Soai reaction offered the first, and to date the only, example of an asymmetric autocatalytic reaction employing a catalyst with a very low enantiomeric excess and ultimately yielding the catalyst with a very high enantiomeric excess catalyst as product.  While the Soai reaction serves as a mechanistic model for the evolution of homochirality, the dialkylzinc chemistry involved in the reaction is unlikely to have been of importance in an aqueous prebiotic environment.  Therefore speculation has continued concerning the types of transformations that might have been directly responsible for the development of high optical activity in biological systems.  The area of amino acid catalysis may hold significant clues to the evolution of prebiotic chemistry.

The paper presents a three-scheme model describing how, given an initial excess of one hand over the other, the products from a second and a third reaction scheme might act as catalysts, producing more reactants for the first scheme.   Here is their model in a nutshell:

We report herein a proline-mediated reaction exhibiting an accelerating reaction rate and an amplified, temporally increasing enantiomeric excess of the product.  Thus, catalysis with amino acids is implicated in an autoinductive, selectivity-enhancing process, providing the first general chemical strategy for the evolution of biological homochirality from a purely organic origin.

This hypothetical self-perpetuating, autocatalytic system might generate an excess of one hand.  The resulting purified mixture, if sufficiently isolated, might then contain the ingredients for primitive proteins.
    They used proline, the fourth-lightest amino acid, for these experiments.  A textbook describes it: “Proline, a cyclic secondary amino acid, has conformational constraints imposed by the cyclic nature of its pyrrolidine side group, which is unique among the ‘standard’ amino acids.”2
    The authors seemed surprised and delighted that the desired reaction sped up.  It was what they sought: “a process whereby the catalyst is improving over time, as in autocatalytic or autoinductive reactions, in which the reaction product either is itself a catalyst or promotes the formation of a more effective catalyst.”  To them, the non-linear rate increase was the signature of an autocatalytic reaction that amplified the desired product: “Amplification of the enantiomeric excess of the product is a key feature of a chemical rationalization of the evolution of biological homochirality.”  Despite earlier researchers’ linear reaction rate curves, that suggested no autocatalytic reaction, they saw a higher than expected rate increase.  “Rate acceleration and continuous improvement of enantiomeric excess are requisite characteristics for chemical models of the evolution of homochirality from precursors of low optical activity,” they noted.
    Some caveats were mentioned.  Cross-reactions of L- and D- reactants had to be prevented, and the environment had to be kept out of equilibrium, or it would have reverted to the mixed-handed (racemic) mixture: “However,” they speculate, “it is important to note that such erosion of enantiomeric excess is predicted only for a closed system such as that occurring in reaction vials in the laboratory.  In an open system, in which catalyst and product fluxes can exist across the system boundaries, the chemical propagation mechanism described in Scheme 1 would permit enantiomeric excess to continue to rise.  Kinetic amplification of enantiomeric excess as observed in the present studies could be sustained,” provided reaction rates between steps in the process are kept in favorable relation to one another, and enough free proline is available as input.  One other thing: since proline might condense with itself, it is unknown whether oligomers of proline would lead to “enhancement or suppression of the nonlinear effect.”  Other potentially damaging cross-reactions that might limit the effectiveness of the autocatalytic process are mentioned.
    Though limited in scope, these experiments lead the authors to believe their work is relevant to a purely mechanistic model for the origin of homochirality:

The experimental observation of an unexpectedly high, accelerating reaction rate and an amplified, temporally increasing enantiomeric excess of product in the proline-mediated aminoxylation of aldehydes is consistent with a mechanistic model for a selectivity-enhancing autoinductive process as given in Schemes 1-3.  This represents the first example of a purely organic reaction exhibiting characteristics that are key to a chemical rationalization of the evolution of biological homochirality.


1Mathew, Iwamura, and Donna G. Blackmond, “Amplification of Enantiomeric Excess in a Proline-Mediated Reaction,” Angewandte Chemie International Edition Volume 43, Issue 25, Pages 3317-3321, Published Online: June 21, 2004.
2Vogt and Vogt, Biochemistry 2nd ed., John Wiley & Sons (1995), p. 60.

Since evolutionists tend to take an inch and boast a mile, we need to bring out the tape measure to keep speculation in check.  In short, under very controlled, hypothetical conditions, one unique amino acid seemed to undergo chemical amplification of one hand.  Does this explain the 100% purity of biological proteins?  You decide.

  1. Only one amino acid was tested, and a unique one at that—proline.
  2. They did not state the value of their best enantiomeric excess.
  3. It is unrealistic to minimize the damaging effects of cross reactions.  Nature would not exclude products that would destroy any “progress.”
  4. It is also unrealistic to depend on open systems.  All real systems, both open and closed, are subject to the laws of thermodynamics.  All real systems, in time, tend toward equilibrium.
  5. The reaction required specialized ingredients and conditions.  For a feeling of this, the following paragraph from their paper is included—not that you need to understand it, but just for a look at the special care they had to take with ingredients and lab conditions.  Ask yourself how much of these special conditions tailored to proline could be generalized to the set of all amino acids, including those with polar and hydrophilic side chains.

    The key to the effectiveness of this system lies in the fact that the reaction product 3 is multifunctional; it is both an aldehyde and an amine.  Scheme 2 suggests that proline 4 may attack the carbonyl group of the reaction product 3 to form the new catalyst 5.  This reaction is virtually irreversible on the reaction timescale, since product racemization was not observed.  This species 5 is a special amine bearing an alpha-oxygen atom with lone pairs of electrons.  The alpha effect describes the unexpectedly high activity of such a nitrogen nucleophile, thought to be due in part to stabilization of the transition state by the lone pair on the oxygen alpha to the nucleophilic atom.  Thus 5 may be a highly efficient competitor to proline for nucleophilic attack on propionaldehyde, forming a new enamine, 6.  This enamine may be competent to attack PhNO, forming a transition state such as 7 by interaction with the carboxylic acid proton as a Brønsted acid cocatalyst.  This leads to the formation of product 3 and regeneration of the improved catalyst 5.

  6. The authors make no attempt to describe a plausible environment in which such specialized conditions would exist on a prebiotic earth.
  7. Any relaxation of the special conditions, and the enantiomeric excess reverses to equilibrium.
  8. The hypothesis is glued together with wiggle words like might, could, may, perhaps, and clues.
  9. Proteins require 100% pure one-handed amino acids.  Close enough is not good enough; the enantiomeric excess has to be 100%.  The addition of one wrong-handed link in a protein can destroy its function.
  10. What about sugars?  Even if a mechanism were found to amplify one amino acid, the sugars in nucleic acids are 100% right-handed.  No plausible naturalistic mechanism for creating nucleotides has been found, let alone purifying them to all one hand.
  11. Natural selection cannot be invoked unless a system can replicate itself with high fidelity.
  12. Remember, chemicals have no desire to evolve.  They are subject to the laws of mass action, thermodynamics, valency, and all the vagaries of their environment.  In a naturalistic world, with no chemist to care, the chemicals are no “better off” in one state or another.  To merely assume chemicals evolved into a living organism is an argument a posteriori based on naturalistic presuppositions.  Without a plausible demonstration of the entire sequence, it is illogical to assume, “We’re here, therefore it happened” (without a designer).

These are just a few of the problems with this story.  What’s more revealing in the paper than the bombast and hype are the damaging admissions.  They admit this has been a problem for over a hundred years, and that only a theoretical approach was suggested half a century ago.  Then, not until 1995 was there any experimental evidence for slight excess of one hand, but even then, the Soai reaction invoked unrealistic conditions for abiogenesis.  So now these authors claim theirs is the first experimental model to show any hope, subject to all the caveats listed above.  Are you impressed?
    Origin of life by the inch is a cinch; by the yard it’s hard (especially to get a yard full of trees, eventually).  We should go the extra mile for someone out of mercy, but not yield the extra inch for illogical and unsupportable claims.  Unwarranted extrapolation is undeserving of mercy.  Chemical evolution must be prosecuted to the full extent of the natural law.

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Categories: Origin of Life

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