Sunday, April 05, 2009

Amino acid chirality

We've discussed the mystery of amino acid chirality – the fact that all biological amino acids on Earth seem to be left-handed. Previous discussion and background are here.

In that earlier discussion we considered a hypothesis that was described last year. It is known that amino acids can be formed in interstellar space. The hypothesis suggests that the first amino acids on Earth were carried here by meteorites. Further, there was some excess of left-handed over right-handed amino acids (but not necessarily entirely the left-handed kind) that arrived this way.

The last detail is to explain how the imbalance of one handedness over the other occurred in space. That could be explained by the fact that light that is strongly polarized could selectively destroy one enantiomer (alternative chiral form of a molecule) of an amino acid. Such light is emitted by rapidly spinning neutron stars. But, as we'll see, there are other possibilities.

This hypothesis was expounded by Ronald Breslow of Colombia University. He has conducted experiments that showed a small initial imbalance could be amplified by successive evaporations of solutions containing phenylalanine, a process that could easily have occurred on Earth. [2] [3]

Although experiments were done to verify the plausibility of the various mechanisms required, there's no direct evidence that the supposed sequence of events is actually responsible for the observed chirality. However, ten years ago analyses of the Murchison meteorite by Sandra Pizzarello and John Cronin did find a preponderance of left-handed amino acids. There was a possibility that this finding could have resulted from some process occurring after the meteorite hit the ground. But last year Pizzarello and others analyzed another meteorite that fell in Antarctica and seemed especially pristine. The researchers reported that there was a similar chiral imbalance in that sample as well, and not only in amino acids but also in precursor aldehydes. [1]

Now there is still more evidence for chiral imbalances – in the Orgueil meteorite, which fell almost 150 years ago:

Clues To A Secret Of Life Found In Meteorite Dust (3/17/09)
Over the last four years, the team carefully analyzed samples of meteorites with an abundance of carbon, called carbonaceous chondrites. The researchers looked for the amino acid isovaline and discovered that three types of carbonaceous meteorites had more of the left-handed version than the right-handed variety – as much as a record 18 percent more in the often-studied Murchison meteorite. "Finding more left-handed isovaline in a variety of meteorites supports the theory that amino acids brought to the early Earth by asteroids and comets contributed to the origin of only left-handed based protein life on Earth," said [Dr. Daniel] Glavin.

There's also evidence about how the imbalance may have occurred:
The team also found a pattern to the excess. Different types of meteorites had different amounts of water, as determined by the clays and water-bearing minerals found in the meteorites. The team discovered meteorites with more water also had greater amounts of left-handed isovaline. "This gives us a hint that the creation of extra left-handed amino acids had something to do with alteration by water," said [Dr. Jason] Dworkin.

The researchers focused on the amino acid isovaline, because it can "preserve its handedness for billions of years, and it is extremely rarely used by life, so its presence in meteorites is unlikely to be from contamination by terrestrial life."

Here's the abstract of the research paper:

Enrichment of the amino acid l-isovaline by aqueous alteration on CI and CM meteorite parent bodies
A large l-enantiomeric excess (ee) of the α-methyl amino acid isovaline was found in the CM meteorite Murchison (lee = 18.5 ± 2.6%) and the CI meteorite Orgueil (lee = 15.2 ± 4.0%). The measured value for Murchison is the largest enantiomeric excess in any meteorite reported to date, and the Orgueil measurement of an isovaline excess has not been reported previously for this or any CI meteorite. The l-isovaline enrichments in these two carbonaceous meteorites cannot be the result of interference from other C5 amino acid isomers present in the samples, analytical biases, or terrestrial amino acid contamination. We observed no l-isovaline enrichment for the most primitive unaltered Antarctic CR meteorites EET 92042 and QUE 99177. These results are inconsistent with UV circularly polarized light as the primary mechanism for l-isovaline enrichment and indicate that amplification of a small initial isovaline asymmetry in Murchison and Orgueil occurred during an extended aqueous alteration phase on the meteorite parent bodies. The large asymmetry in isovaline and other α-dialkyl amino acids found in altered CI and CM meteorites suggests that amino acids delivered by asteroids, comets, and their fragments would have biased the Earth's prebiotic organic inventory with left-handed molecules before the origin of life.

Note that evidence in the samples analyzed was not consistent with circularly polarized light as a cause of the imbalance, and a process involving water seems more likely.

Other accounts of this research: [6], [7]

There's other relatively recent research that demonstrates another way enantiomeric excesses of one form of amino acid could be produced. When inorganic materials are irradiated with high-energy photons (e. g. X-rays), they may emit electrons whose spins are polarized in a specific direction by a magnetic field. Experiments showed that this could affect the chirality of organic molecules adsorbed on the surface of a magnetic material:

Electrons put a new spin on chirality (11/5/08)
Researchers in the US have shown that the presence of spin-polarized electrons can make a chemical reaction involving “right-handed” molecules occur faster than the same reaction involving “left-handed” molecules. The discovery could help scientists understand why nature favours a certain handedness in many biological molecules.

Although the organic molecule used in this experiment was butanol (not an amino acid), the researchers plan to perform a similar experiment with the amino acid alanine. While this research doesn't show this is the mechanism actually responsible for left-handedness of amino acids found on meteorites, it's a least a possibility.

Press release on this research: [4]
Glavin, D., & Dworkin, J. (2009). Enrichment of the amino acid L-isovaline by aqueous alteration on CI and CM meteorite parent bodies Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0811618106

References and further reading:

[1] Key To Life Before Its Origin On Earth May Have Been Discovered (2/28/08)

[2] Amplification of enantiomeric concentrations under credible prebiotic conditions – July 2006 research paper by Ronald Breslow and Mindy S. Levine

[3] Radiation-induced racemization and amplification of chirality: implications for comets and meteorites – February 2007 research paper

[4] Possible Mechanism For Creating 'Handedness' In Biological Molecules (12/2/08)

[5] Rock Offers Mirror-Image Clues to Life's Origins (10/5/08) – good overview article in the Washington Post

[6] Did lefty molecules seed life? (3/16/09) – The Scientist

[7] Southpaw Solar System (3/16/09) – ScienceNOW


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Sunday, May 04, 2008

The amino acid chirality mystery

If the analysis here is correct, it solves one of the more puzzling mysteries of life on Earth – namely, the fact that all 20 amino acids found in biological proteins are "left-handed".

Meteorites Delivered The 'Seeds' Of Earth's Left-hand Life, Experts Argue
In a report at the 235th national meeting of the American Chemical Society, Ronald Breslow, Ph.D., University Professor, Columbia University, and former ACS President, described how our amino acid signature came from outer space.

Chains of amino acids make up the protein found in people, plants, and all other forms of life on Earth. There are two orientations of amino acids, left and right, which mirror each other in the same way your hands do. This is known as "chirality." In order for life to arise, proteins must contain only one chiral form of amino acids, left or right, Breslow noted.

"If you mix up chirality, a protein's properties change enormously. Life couldn't operate with just random mixtures of stuff," he said.

Recall that a carbon atom can form up to four bonds with other atoms. (Sometimes there are 2 or more bonds with the same atom, such as a double bond to another carbon atom.)

You can imagine these bonds arranged in a tetrahedral shape, that is, from a central carbon atom in the direction of the 4 vertices of a tetrahedron. In an amino acid, three of the bonds are occupied by a hydrogen atom, an amino group (NH2), and a carboxyl group (COOH). The remaining bond is occupied by a fourth group, which is variable (but there are only 20 possibilities that normally occur in Earthly biology) and determines the specific amino acid. The simplest amino acid is glycine, in which the fourth bond is occupied by a single hydrogen atom.

If you think of the amino acid as a tetrahedron, with the carboxyl group at the top, the other three components are arranged around the three bottom vertices. In glycine, two of those positions will be hydrogen atoms. But in all other amino acids, there are two different orders in which the distinct components can be arranged. Think of the tetrahedron's axis running from the central carbon atom to the top. If you look down that axis towards the base of the tetrahedron, then the hydrogen atom will be in either the clockwise or counterclockwise direction from the amino group. The latter is (by convention) called the left-handed (L) version, and the former is called the right-handed (R) version.

A protein is a series of amino acids tied together by peptide bonds, which form between the amino group of one amino acid and the carboxyl group of the other (with an H2O molecule removed, since an H pairs with an OH). In biological proteins such bonds form only between amino acids of the same chirality (both R or both L). So all proteins must consist only of L or R amino acids. As it happens, only the L type of protein occurs in nature on Earth. Presumably that is because at some time back when life was first developing, L amino acids significantly outnumbered R amino acids, and hence L proteins predominated over R proteins.

So the mystery is reduced to that of why at some point in time there were many more L amino acids than the R form. It has been shown that amino acids can form spontaneously from inorganic materias under some conditions (the Miller-Urey experiments demonstrated this.) However, one would expect equal amounts of R and L amino acids under such circumstances.

But there's another way out, because we know that in fact amino acids can form in interstellar space, since they were found in parts of the Murchison meteorite (and later others) that were uncontaminated with Earthly material. Furthermore, there's one definite way that amino acids which existed originally in an equal mixture of L and R forms on a chunk of rock hurtling through space could have their proportion tilted in one direction or the other:
These amino acids "seeds" formed in interstellar space, possibly on asteroids as they careened through space. At the outset, they have equal amounts of left and right-handed amino acids. But as these rocks soar past neutron stars, their light rays trigger the selective destruction of one form of amino acid. The stars emit circularly polarized light--in one direction, its rays are polarized to the right. 180 degrees in the other direction, the star emits left-polarized light.

All earthbound meteors catch an excess of one of the two polarized rays. Breslow said that previous experiments confirmed that circularly polarized light selectively destroys one chiral form of amino acids over the other. The end result is a five to ten percent excess of one form, in this case, L-amino acids. Evidence of this left-handed excess was found on the surfaces of these meteorites, which have crashed into Earth even within the last hundred years, landing in Australia and Tennessee.

So, one asks, is it possible that this imbalance of R and L amino acids was transferred from a meteorite to prebiotic Earth? In a series of experiments Breslow confirmed that this could happen:
Breslow simulated what occurred after the dust settled following a meteor bombardment, when the amino acids on the meteor mixed with the primordial soup. Under "credible prebiotic conditions"-- desert-like temperatures and a little bit of water -- he exposed amino acid chemical precursors to those amino acids found on meteorites.

Breslow and Columbia chemistry grad student Mindy Levine found that these cosmic amino acids could directly transfer their chirality to simple amino acids found in living things. Thus far, Breslow's team is the first to demonstrate that this kind of handedness transfer is possible under these conditions.

On the prebiotic Earth, this transfer left a slight excess of left-handed amino acids, Breslow said. His next experiment replicated the chemistry that led to the amplification and eventual dominance of left-handed amino acids.

That's where things stand now. We have as yet no way of knowing whether this is the scenario that actually occurred. But it is the most credible scenario yet devised to explain the otherwise astonishing fact that essentially all life on Earth uses only left-handed amino acids.

Further reading:

Meteorite source for life's handedness (4/8/08)

Did a Cooked Meteorite Seed Life on Earth? (4/6/08)


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Saturday, October 21, 2006

Intrinsically unstructured proteins

It's long been the conventional wisdom that proteins have rigidly fixed shapes which are crucial to their function – at least those proteins which actually have important functions. But now, apparently, not so much:

First Major Study Of Mammalian 'Disorderly' Proteins
Unlike the classic description of proteins described in science textbooks, IUPs are not completely locked into rigid, 3-D shapes that determine their function in the cell. Instead, IUPs have varying amounts of flexibility within their sometimes spaghetti-like structures that is critical for function. For example, one protein named p27 initially looks like a Slinky™ toy. However, when p27 goes to work, it puts a vise-like grip on an enzyme that otherwise would promote uncontrolled cell division.

The St. Jude team developed a technique that uses heat to isolate IUPs in large, purified quantities from extracts of a standard type of cultured mouse cells called NIH3T3 fibroblasts. The IUPs were resistant to the heat, unlike more structured proteins, which fell apart. Based on these studies, the investigators were able to classify all proteins into one of three categories: IUPs; intrinsically folded proteins (IFPs, i.e., fully folded into specific shapes); or mixed ordered or disordered proteins (MPs), which have both structured and unstructured parts.

The point isn't that protein scientists have been wrong all this time, so much as that nature will often be able to find a use for building blocks in order to take advantage of varying characteristics that are available.

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