Origin of biological chirality & natural left preference

– A brief yet fascinating insight on Nature’s knack to write life with its left hand

Introduction –

Almost every other high school student who has taken science classes has deliberately come across the word ‘Chirality’. It derives from the Greek word for hand χειρ (kheir) & stands for ‘handedness’. Chirality is a phenomenon that is not only restricted to the world of chemistry but it is seen in many fields like physics, mathematics & of course in our day to day life.

It was in 1874, Jacobus Henricus van’t Hoff & Joseph Le Bel came with what I believe is one of the most revolutionary ideas in Chemistry, the very concept of tetrahedral disposition of the four valences of a Carbon atom. This later on lead to the advent of “Stereochemistry” (Organic Stereochemistry in this context). A very important field that has now become utterly crucial, especially in the biological world where not only connectivity of various atoms or groups of atoms is important but also their spatial disposition in a given chemical environment.

Putting it simply, we are interested in only that kind of stereochemistry here where we have a Carbon atom & four atoms or groups of atoms attached to it (say L1, L2, L3 & L4). Each of them pointing at the vertex of a tetrahedron. This kind of a Carbon is said to be “sp³ hybridized” by us chemists. A unique & very fascinating feature arises to such a Carbon atom if L1, L2, L3 & L4 are all different groups. By the term “different” I mean (here) that they are chemically different. In such a special case of arrangement of all these L’s around our Carbon atom we see that the mirror images of such an arrangement is non super imposable on the arrangement which generated it! No matter how hard you try, you’ll never be able to superimpose these two dispositions with each other without breaking a C-L bond.

You might think how & why is this so fascinating? The answer to that is, these two different dispositions are exactly identical in terms of the number & kinds of atoms involved to form them. They are exactly identical in terms of the mode of bonding adopted to form such an arrangement. But the only place where they differ is in the “Spatial Orientation” of the L groups around the central Carbon. This very difference is enough to alter the properties of them depending on their “Chemical Environment”.

To understand the concept of “Chemical environment” let’s look at a very frequently encountered situation from our day to day lives. Our “social behavior” is sensitive to the social environment surrounding us. You don’t wear disco clothes to a classroom. You don’t laugh out loud in front of a dying patient in a hospital. This is because the very “sense” of how to behave like this or that is blue printed in our brain. Some of these senses are acquired & may or may not change with time whereas some of these senses are a result of the natural course of evolution & is inherently programmed into our biological systems (hard wired into our brains).

Similarly these special molecules we were discussing are of significant interest in Chemistry & other associated fields because these molecules are “smart” & they have a “sense” of geometry. They know how to behave depending upon their chemical environment. Which means that they can interact with the other molecules around them in a way that is unique to them. The very origins of such “special interactions” can be traced back to chirality. Chirality is a very important from of molecular recognition that has been ever encountered.

In this article I will try to very lucidly discuss the miraculous observation that “Why Nature prefers left handed amino acid molecules over the right handed ones”? However I feel it is extremely essential to mention that so many scientists have tirelessly worked behind this difficult question (one of the greatest challenges in Biochemistry & Astrobiology) & all of this is a cumulative effort. While none of them have been able to be surely pin point a definitive reason to this peculiar choice of Nature but we do have few hypotheses which offer a plausible explanation. We hope than in near future with the fast paced advancement of Science we will come to something definitive & unravel the mysteries surrounding Nature.

Article –

Amino Acids & Proteins – A brief overview

Amino acids are the building blocks of proteins. They can be simply viewed as a tri substituted Methane (CH₄) derivatives. Amino acids are just an excellent example of the special molecules I just discussed in the introduction above.

They have the following general structure

This makes the central carbon chiral & thus it can exist as a pair of enantiomers (molecules with a non –super imposable mirror image relationship). The R group is called the variable group & different R’s five different amino acids. The other three groups are common features of any amino acid.

There are 20 naturally occurring amino acids & they react with each other in a biologically instructed sequence to form what are known as polypeptides(a chain of many peptide linkages).

Just like we have 26 alphabets in the English language which combine in different ways to form words, these 20 naturally occurring amino acids serve as chemical alphabets & the chemically combine (bond) in different combinations (biologically instructed sequence) & give rise to different proteins (huge polypeptides).

Proteins are very important in almost any biological system. They are used I several 1000 biological pathways & are absolutely indispensable molecules towards life. So they have interested a lot of Physicists, Chemists & of course Biologists.

A brief discussion on an experiment which discusses the chemical origin of life – The big question, WHAT IS LIFE?

Several theories have been proposed for the origin of life. Some very bizarre ones & some very elegant ones.

The one that I will very briefly discuss here is the famous “Urey Miller Experiment” done in 1952 by Stanley Miller & Harold Urey at the University Of Chicago & later the University of California, San Diego.

They were exploring the chemical origin of life & this I personally believe was a very logical way at looking for a possible origin of life.

In this experiment they basically tried to mimic (simulate) the physicochemical conditions that were presumed to be present on the early Earth.

Miller & Urey reported the identification of 5 different amino acids in 1952. In 2007, Jeffrey Bada, a student of Miller, further examined the original unused vials of Miller from early 1950s.

Using more modern & sophisticated experimental techniques like HPLC (High Performance Liquid Chromatography) & MS (Mass Spectrometry) it was found that the vials had much more organic molecules than those estimated by Miller in 1952. It was found that 22 amino acids are present in those very vials where Miller could detect only 5 of them at his time.

Paul Ehrlich (a German Physician & Scientist, also the recipient of the Nobel Prize in physiology in 1908) as a schoolboy once said that “Life is a chemical incident”.

I feel that these words are so powerful that they can leave you transfixed if you look at the origin life from a chemical point of view. How wild is it to imagine that we are just an aggregate of a huge collection of atoms, molecules & ions, so carefully crafted together. I mean the very thought of it just drives me crazy!

Back to the main question now – Why did Nature write life with its left hands?

Several scientists have worked a lot to try & answer this difficult question presented above. We see that only left handed amino acids are proteinogenic. Which means that only left handed amino acids are incorporated biosynthetically into proteins in our cellular machineries.

When I mentioned the Urey-Miller experiment above, I smartly avoided the question of chirality of the amino acids that were observed in Miller’s vials in 1952 and 2008. I will now introduce that question here. As mentioned before, the Urey-Miller experiment tried to simulate the physicochemical conditions present on early Earth. And we see that life forms on our planet Earth have the left handed or L amino acid as the proteinogenic ones.

(Caution: L is not standing for left here! It is “Stereo descriptor” that we chemists use to identify enantiomers. Readers are requested to kindly refer to any standard Organic Chemistry textbook for further details)

So in a real early Earth situation, something must have happened that lead to this bias towards the L amino acids & their extensive biological participation in all the life forms we see today. So did Urey & Miller identify only L amino acids in their experiment? The answer is NO!

Here comes a huge plot twist!

…Ready For It?

It was experimentally observed that both left handed (L) & right handed (D) (for further details lookup a standard Organic Chemistry text please!) optical isomers.

(Optical because these differently handed molecules interact with a special form of light in different ways, readers are advised to look through a standard Organic Chemistry textbook for further details)

But in biological systems it is well known that almost all compounds which exhibit chirality are non-racemic, i.e. only one particular handed form of them is present & not a mixture of both. So what extra thing did early Earth have that led to the creation of this molecular bias? Is there any well-defined mechanism that can explain this? Or was it completely a random thing? The debate still goes on amongst scientists & the answers to all these questions are inconclusive.

Scientists have traced back a plausible explanation to this natural molecular bias to the outer Space!

(I bet you did not see that coming but don’t worry, we’re on the same boat)

Researchers & NASA Scientists analyzed meteorite fragments that fell on a frozen lake in Canada to look for any possible explanation for the origin of life’s handedness. Their analysis revealed that water percolating through the asteroids must have played an important role in making the left handed amino acids that is found in all known life forms on Earth.

Previous research notifies us with the fact that synthetic (man-made in lab) proteins made up of mixed L & D amino acids simply don’t “work” biologically. This provides support to the fact that biological systems are homochiral.

Further studies on the amino acid content in the Lake Tagish (Canada) meteorite left the scientists baffled.

Liquid chromatographic & mass spectroscopic studies revealed that Aspartic Acid has a 4x excess of L form relative to the D form, this was as per the natural expectations. But the same sample showed a very slight excess (appx. 8%) of L form relative to the D form for Alanine. They finally concluded using isotopic analysis that these main acids being sampled were probably created inside these asteroids itself by some non-biological processes, as they had high contents of C-13 isotope of Carbon.

This C-13 enrichment along with the large left hand excess for Aspartic Acid provided strong evidence that some left handed proteinogenic amino acids that were once used by life to make proteins could have come from outer space.

Another group of scientists suggest that this large excess of left handed amino acids could arise from the interaction of the polarized electromagnetic radiation in solar nebula. Electromagnetic radiation consists of two vectors, the electric filed vector (denoted by E) & the magnetic field vector (denoted by B or H). These two vectors are mutually perpendicular to each other & they undergo periodic oscillations in all possible directions & the electromagnetic wave travels in a direction simultaneously perpendicular to the direction of these two field vectors.

Polarization (here) means that we are filtering off the oscillations of these field vectors from all possible directions to a particular direction of our choice by using a Polaroid.

Circular polarization is a special type of polarization (for further details, the readers are requested to kindly lookup any standard text book on Electrodynamics) that exists. In case of a circularly polarized electromagnetic radiation, the E vector doesn’t change in magnitude but it does rotate in a circular fashion & continuously changes its direction.

This type of polarization has been observed in Cat’s Paw nebula (located in the Scorpius constellation, 5000 light years away from us).

A team of astronomers at the National Astronomy Observatory, Japan discovered that about 22% of the Cat’s Paw Nebula is circularly polarized. This suggests that circular polarization maybe a common feature of star formation & could’ve potentially channelized this molecular bias in an indirect form.

Scientists suggest that the amino acids which were forming in the environment of this circular polarization could’ve been favored by the direction of the polarization & those “in sync” with the direction of polarization will be formed in an excess amount. The implications of this idea are multifold. We can exploit this idea (of course if we prove it) in the field of Synthetic Chemistry too. Just imagine the industrial & laboratory scope of such a phenomenon!

Conclusion –

Well the whole thing is pretty much inconclusive & its nascent stage right now. We hope that in future with the swift advancement in science we’ll be able to unravel this mystery of life. But let’s take a moment to encourage the fact that we have done some very good amount of research to get this question answered.

The origin of life, I believe is certainly chemical & I think this unanswered question can only be answered if we have intensive collaborative research which is well coordinated amongst out astronomers, astrophysicists, astrochemists, astrobiologists & biochemists.

Chirag Arora

Chemistry undergraduate

Dept. Of Chemistry

St. Xavier’s College, Kolkata

Link to his own blog : https://chemchirag13.wixsite.com/lumierelmi

References –

Origin of biological chirality & natural left preference

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