Friday, April 24, 2009

Can watery asteroids explain why life is 'left-handed'?

It's time to re-visit the so-called "racemization" or "chirality" problem. The "problem" is thought to be the absolute preference for left-handed amino acids in living organisms.

Naturally occurring amino acids are racemic mixtures of both L- and D-amino acids. How did life come to select only one of the two possible stereoisomer for making proteins?

Sandwalk readers will know that I prefer an evolutionary explanation. In the beginning there were only a small number of amino acids that combined to make catalytically active peptides. One of these might have been glycine, which doesn't have L- and D- forms. Glycine might have formed spontaneously from acetate or glycerol.

Next came other simple amino acids whose biosynthesis might have been assisted by short polyglycine peptides with a few other naturally occurring amino acids. The peptides are biological catalysts, like modern enzymes only less efficient. It's possible that the primitive pathway might have favored the synthesis of amino acids like L-alanine and/or L-serine. (Many enzymatically catalyzed pathways are stereospecific—they make only one of the two possible forms.) The accumulation of L-alanine and L-serine could have been entirely by accident. It could just as easily have been D-alanine and D-serine.

Once the simple amino acids started to accumulate by biosynthesis, additional pathways started to evolve and more amino acids were added to the mix. These additional amino acids were all derived from the simple ones so they too were exclusively L- forms. Eventually life evolved from this chemical mixture and all the pathways were making the same form of amino acid. This process would have had to take place in a "warm little pond" in order to produce appropriate concentrations of the amino acids (and other things).

According to this scenario, the exclusive presence of L-amino acids instead of D-amino acids is just an accident. The fact that all amino acids are of the same form as the first ones is just a consequence of the fact that more complicated pathways started with the first ones as precursors.

Is there another theory? Yes there is. Some people think that life began in a soup containing all twenty or so common amino acids. They believe that all these amino acids formed spontaneously by chemical reactions rather than by the evolution of primitive catalysts from simple peptides.

Some people believe that the amino acids, and other chemicals, formed in outer space and they were delivered to Earth in meteorites. There has long been evidence that meteorites contain amino acids, lending support to this explanation.

Does this solve the chirality problem? No, it doesn't, because the amino acids found in meteorites are mixtures of L- and D-forms. People who support the idea that all twenty amino acids were present from the beginning would have to account for the selection of only one form from the mixture. Since this is highly unlikely, most favor a solution where some form of chemical synthesis preferentially results in a huge excess of left-handed amino acids. So far no example of such a reaction has been found.

On the other hand, there are hints that such a chemical reaction might be possible. There are 74 different amino acids in the Murchison meteorite and all of them are racemic mixtures (L- + D- forms). But in some cases there's a slight excess of the L- form of the amino acid suggesting that chemical formation of amino acids in outer space may favor the left-handed version—the same version that's found in living cells.

A recently published paper shows that the slight excess of one amino acid, isovaline, is enhanced by formation in liquid water (Glavin and Dworkin, 2009), giving rise to a press release that was reported in New Scientist as Watery asteroids may explain why life is 'left-handed'.

The scientific paper examines the chirality of amino acids found in several different meteorites. The main finding is that there's an excess of L-isovaline over D-isolvaline in most samples. The excess can be as high as 18%. Most other amino acids have equal amounts of the L- and D-forms.

Isovaline is not one of the naturally occurring amino acids found in protein and the difference is significant. All 20 of the common amino acids have a structure like that shown on the left of the figure below. The central carbon atom (called the α-carbon) is attached to an amino group (—NH3+) and a carboxyl group (—COO-). The carboxyl group makes it an acid and that's why these compounds are called amino acids.

Each carbon atom can have four covalent bonds. In the standard amino acids one of the other groups is always a hydrogen atom (—H). The other is a side chain shown as "R" in the figure. If the four groups bound to the α-carbon atom are different then the amino acid will exist in two different forms; L- and D-.1

The simplest amino acid is glycine where the R group is just a hydrogen atom. Thus, glycine is not a chiral compound and there's no such thing as L-glycine or D-glycine. All other natural amino acids are chiral.

Valine has a R group consisting of a branched 3-carbon chain. Isovaline, which is not a natural amino acid, is quite different. The hydrogen group found in all the standard amino acids is replaced by a methyl group (—CH3).

Why is this important? It's important for two reasons. First, because isolvaline is extremely rare on Earth you can be confident that the meteorite isn't contaminated by isovaline from living organisms. Second, all amino acids will spontaneously undergo racemization, or conversion of L- forms into D- forms and vice versa. Over million of years this reaction will lead to equal amounts of the two forms. With amino acids like isovaline, where there are four large chemical groups bound to the α-carbon atom, the rate of this reaction is very slow (billions of years rather than 10 million years).

The paper by Glavin and Dworkin suggests that there may be natural chemical processes leading to an increase of one stereoisomer over the other and this natural preference for L-amino acids may be the reason why life selected the L- forms over the D- forms. Because isovaline is so stable it may preserve the original bias that has been lost in the case of the other amino acids.

In order for extraterrestrial organic matter to have fueled the origin of life, a lot of meteorites carrying organic matter had to arrive on the primitive Earth. The problem of amino acid concentrations and stabiltity were discussed in a classic paper by Jeffrey Bada published in 1991.

Some of his calculations are worth remembering.

The current flux of extraterrestrial organic material is about 3 × 108 grams per year from cosmic dust and micrometeorites. About 1% of this is amino acids and most of them are not the ones found in living organisms. This should give rise over time to a concentration in the oceans of about 0.1 nM (10-10 M). That's not sufficient for life to have originated.

The flux in the past was almost certainly much greater and lots of organic material might have been delivered by large meteorites; however, it's unlikely that amino concentrations in the oceans could ever have been more than 10-100 pM for all amino acids combined.

Most amino acids will spontaneously degrade over time. There's a window of opportunity that only lasts about 10 million years because in that time all the water in the oceans will pass through hydrothermal vents and the high temperature will destroy most chemicals—including amino acids.

Bada concludes with ...
There are no known effective abiotic processes for generating chiral amino acids, which suggests that on the early Earth, only racemic amino acids would have existed. Because of the problem of racemization, it is likely that only after biotic protein synthesis became an efficeint process in the evolution of early life could the chirality of amino acids be maintained in proteins. Instead of amino acid chirality preceding the origin of life, it may have developed after life was well established, and possibly in close association with the origin of protein biosynthesis. As to why the protein amino acids consist only of the L-enantiomers, it is probably just a matter of chance.
The important lesson here is that there are several different scenarios leading to the preference for L- amino acids. It's wise to keep in mind that abiotic (chemical) synthesis of amino acids with a bias for the L- forms is not the only possibility.

1. It's better to call these L- and D- forms of the amino acids rather than "left-handed" and "right-handed." The "handedness" refers to the direction in which the stereoisomers rotate polarized light and in modern terminology there is no obligatory connection between the L- designation and the optical activity. As it turns out, most of the L-amino acids are also l-amino acids (levorotary = left-handed) actually d-amino acids (dextrorotary = right-handed), but there are some exceptions. L-cysteine, for example, is "right-handed" truly "left-handed" (see Specific Rotation and Temperature Coefficients of Amino Acids). Thanks to DK (see comments) for correcting my earlier mistake.

Bada, J. (1991) Amino acid cosmogeochemistry. Phil trans. R. Soc. Lond. 333:349-358.

Glavin, D.P. and Dworkin, J.P. (2009) Enrichment of the amino acid l-isovaline by aqueous alteration on CI and CM meteorite parent bodies. Proc. Natl. Acd. Sci. (USA) 106: 5487-5492 [DOI: 10.1073/pnas.0811618106]


  1. most of the L-amino acids are also l-amino acids (levorotary = left-handed), but there are some exceptions. L-cysteine, for example, is "right-handed." "Some" exceptions? I was under impression that majority of common L-amino acids are dextrorotary. See, for example, here. But Wikipedia says that only 9 out of 19 are (at 589 nm). In any case, chirality conventions are a mess and you probably meant to say that cysteine is the only one that has (R) absolute configuration.

  2. DK writes,

    I was under impression that majority of common L-amino acids are dextrorotary. See, for example, here.You are correct. I didn't pay attention when I first looked at the table.

    I've edited my posting.

    Thank-you very much.

  3. Link to New Scientist article is broken.

  4. Link to New Scientist article is broken.

    Thanks. I fixed it.

  5. hello there moran. great website. by any change do you have a twitter account were you update your post? Thanks. did you read about the 'What Came First in the Origin of Life? New Study Contradicts the 'Metabolism First' Hypothesis', can you write something about it?