OOL VI - Chirality and Sugars.

From: Perplexed in Peoria (jimmenegay_at_sbcglobal.net)
Date: 03/09/05 

Date: Wed, 9 Mar 2005 01:56:32 -0500 (EST)

One of the things that distinguishes organic chemistry is the possibility
of chirality. I had originally intended a full posting or two regarding
chirality, but Larry Moran has called my attention to this essay that he
produced for "the other place". It says just about everything I wanted to
say on the subject, and it also shows that at least some of the ideas I am
suggesting here are not all that unorthodox. It is worth a look, even
though it does not share my assumptions regarding autotrophy.
http://groups-beta.google.com/group/talk.origins/msg/083969befdafeca7

It may also be worthwhile to take a look at a paper by Benner and
Ellington which appeared in CRC Critical Reviews in Biochemistry (vol 23,
issue 4, 1988). They discuss the difficulty of distinguishing "fossil"
evidence from evidence of more recent selection. I have tried to use
their methodology as much as possible in constructing my theories. This
paper also touches on the chirality question in a backward sort of way.

So far, in terms of reactions, we have looked primarily at nucleophilic
substitutions - connecting and disconnecting building blocks, and changes
in the N, O, and S groups that "decorate" the carbon skeletons of
molecules. We have also seen some redox reactions, which interchange an H
substituent at a carbon with an N, O, or S. In this posting, we begin to
look at reactions that change the carbon skeletons - that create or
destroy carbon-carbon bonds.

I will classify these reactions into three broad categories:

1. Rearrangements. These shift the bonding within a single molecule.
They are fairly uncommon in biochemistry, though there is an interesting
example of an Amadori rearrangement in the synthesis of valine and
isoleucine:
http://biocyc.org/ECOLI/new-image?type=PATHWAY&object=VALSYN-PWY&detail-level=4
There are also some Dimroth rearrangements in the co-enzyme pathways. I
will have nothing to say about these, other than to point out that they
may seem mechanistically difficult if you have only studied biochemistry,
but if you have also studied organic chemistry, they can be seen to be
easy and not to require much catalysis.

2. Carbon fixation (and decarboxylation). These create (and destroy)
carbon-carbon bonds between organic molecules and inorganic carbon sources
such as CO2 or HCN). Clearly, a strictly autotrophic theory of life's
origin must account for carbon fixation. This will be the main subject
matter of my next posting, and will be revisited in later postings. It is
only a slight exaggeration to say that accounting for carbon fixation at
each stage of life's existence is THE central problem in OOL.

3. Condensation (and cleavage). These reactions join (or separate) two
organic molecules with the creation (destruction) of a carbon-carbon bond.
These are the subject of this posting.

These are not easy reactions to catalyze. In modern biochemistry, there
is almost always a co-enzyme which acts as a carrier for one of the two
organic molecules and also assists with the catalysis. The two most
important are pantotheine (CoA) and thiamine. Each of them participate in
a large variety of reactions. Here we will focus on thiamine and its role
in the reactions of sugar metabolism - though its role in the citric acid
cycle and in the biosynthesis of valine is also interesting. (Same basic
reactions, but a difference in what is being carried).

Take a look in your favorite biochem text at the trans-ketolase reactions
of the Calvin cycle. In each of them, a phosphorylated sugar (of length
N, say) is cleaved by thiamine into a phosporylated sugar of length N-2.
The two carbon sugar remainder is bound to the thiamine. Then this two
carbon moiety is transfered to a second phosphorylated sugar, extending
its length from M (say) to M+2.

Your text can tell you all about the reaction mechanism. But I want to
call your attention to those phosphate groups on the sugars. They don't
participate in the reaction at all. Why are they there? Well, one can
certainly construct a rationalization of this. Perhaps the phosphates
assist in binding substrate to enzyme; or perhaps their charge serves to
prevent intermediate metabolites from escaping through the membrane.
However, I want to explain them the same way I explained carboxylate
groups in my previous posting. I claim that these phosphates are fossils
of the RNA world. In that world, they served as "handles".

So, if phosphates, like carboxylates, were handles, what were the
carriers? Two possibilities - the 5' end of an RNA macro-molecule, or
the 3' end of an RNA macro-molecule. I'll let you explore what this might
mean in the shikimate pathway and other pathways and reactions involving
sugar substrates. But I definitely want to call your attention to what it
means when the phosphorylated sugar is ribose and when the carrier is the
3' end of an RNA molecule. Notice that the ribose then has exactly the
same linkage as in nucleic acids. Is it possible that purine and
pyrimidine synthesis took place, not just on a PRPP template, but on an
RNA + phosphate + ribose template?

Having mentioned transketolase, I should also mention aldolase.
There are two completely different enzyme families that catalyze this
reaction - interesting because it suggests that these enzymes were created
after the MRCA. But the function must have existed before the MRCA, in
fact, probably in the RNA world. In one of these two families, a lysine
group acts as a "coenzyme within the enzyme". I would suggest that in the
RNA world, this functional role was served by some other (less floppy)
amine - perhaps by pyridoxamine.

I would also note that in the aldolase reaction, there are two
phosphate handles and hence two carriers. If the reaction were to take
place on a sugar with only one handle, then we would have a simple soluble
organic intermediate metabolite, and I deny that such things existed in
the RNA world.

Slogan: Find the handles! Phosphates and carboxylates in modern
          biochemistry are the fossils of carrier attachments in RNA world
          biochemistry. If there are no handles, then the reaction is not
          an RNA world reaction.

Is there any real conclusive evidence for this hypothesis? No, but I
think that if you look at enough biochemical reactions and pathways using
this point of view, the weight of the circumstantial evidence will begin
to seem overwhelming. In any case, I said at the outset of this series
of postings that my goal was not to convince anyone, but merely to
explain the viewpoint I have selected and to present some of my reasons
for adopting this viewpoint. Conclusive evidence for this model of
RNA world metabolism simply doesn't exist. But we have to work with some
kind of model - if only to have something that can be refuted by
contrary evidence that we are not aware of. Plus we need a model of
the RNA world if we are to have any chance of creating a model for
the world that preceeded it or a model of the origin of translation
and the transition to the modern world.

Progress in science is made by taking a bold, but risky, stance. I
think that one of the reasons J. T. Wong was unsuccessful in promoting
a theory similar to this one is that he tried to make his theory too
weak and too immune to contrary evidence. In fact, in many of his
papers, he didn't even mention the aspect that is central here -
that metabolism is hypothesized to have taken place on tRNA carriers.
Perhaps I have gone too far to the other extreme. Time will tell.

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