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It isn’t just biomolecules that show chirality. There is also
chiromorphology, like snail shells that usually turn to the right
(dextral, or D-). There are factors in early embryonic
development that cause the body and shell to be right handed
in most gastropod species, yet other species are left handed.
There are also instances where a right-handed species will
produce a left-handed individual, so shell collectors have to be
on the look out for abnormal individuals.
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What isn’t amazing
is that it happens to be L- for amino acids and D- for carbohydrates; the fact that they’re
different is no big deal. Evolution just wants the parts to fit together, so if
an enzyme evolved to use D-sugars, it’s not a surprise that the D-sugar would
be favored in the pathway then now on.
But it might not have been random either. No one knows for sure,
but hypotheses abound for how homochirality in these biomolecular monomers was established.
One 2009 paper was concerned with the maintenance of
homochirality rather than its establishment. Dr. Soren Toxvaerd stated
that if you don’t believe life as we see it today occurred in a singular event, then it must have
developed over a long period of time. Evidence indicates that small changes in
the self-assembly of biomolecules took place over at least thousands of years.
If life took a long time to develop, then prebiotic (before life) earth must have been fairly stable in terms of
enantiomer concentrations. But we know that homochiral solutions will turn to racemic mixtures (containing both L-
and D- enantiomers) in a short time, days for amino acids and just hours for
sugars. So how could the environment have been stable enough for life to
develop over time?
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One possible hypothesis about the establishment of homochirality
was put forth in 2010 by Koji Tamura, PhD in the Journal of
Cosmology. Put very simply,
RNA may have developed before
proteins. RNA evolved to use only D-ribose because a mixture
would have been a symmetry violation. The action of D-ribose
would have been driven toward L-amino acids because of shape
problems with attaching D-amino acids to tRNAs. Now prove it.
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What is more, hydrothermal vents and black smokers have just
the needed conditions for both chiral discrimination and for self-assembly of
biomolecules. Interesting huh? Think it’s a coincidence that black
smokers harbor some of the oldest archaea on Earth? We may owe our very
existence to plumes of superheated water and the xenophobia of enantiomers.
Lastly in this area, it may be that sugars and amino acids selected each other for homochirality. Glyceraldehyde is 1) highly
discriminate for its enantiomers, 2) was present in large amounts in prebiotic
oceans, 3) is used in self-assembly of many biomolecules, and 4)
D-glyceraldehyde very much likes to bind to L-serine. So a slight excess in
either one of these could have helped select for the other, and if this was
stable, it could have caught on like “Gangnam Style.” This may be why life uses
mostly D-sugars and L-amino acids and
why I know the name Psy.
Now that we have delved into the mire that is maintenance of
homochirality in sugars, let’s look at the rule breakers. D-sugars aren’t the
only game in town.
Bacteria, oh bacteria! Once again, they lead the way in rule breaking. Last week we discussed how E.coli can generate ATP from several different sugars - glucose, lactose,
etc. It takes different enzymes to metabolize each sugar, so if they are going
to invest the energy in maintaining those genes and making those enzymes, there
better be a good reason.
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Paracoccus species 43P
has been shown to have an L-glucose
metabolic pathway. This organisms is very closely related to
Paracoccus
denitrificans. P. denitrificans is
believed to be the
organism that was engulfed to become the eukaryotic
mitochondrion. It closely resembles the mitochondrion, and
although random genes needed for aerobic respiration have
been found in many prokaryotes, P. denitrificans is the only
prokaryote in which all the
necessary genes have been found.
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Mammals can’t manage as well as some bacteria; we can’t
metabolize L-glucose at all. However, that doesn’t mean it can't work for us.
L-glucose has been proposed as an artificial sweetener, especially for type II
diabetics. One form of L-glucose can stimulate insulin release, so this would
be doubly good for type II diabetics. Unfortunately, L-glucose costs 50% more
than gold; therefore, don't look for it next to the Truvia anytime soon.
One, but only one, study has been published showing rats
metabolized L-fructose and L-gulose, but not L-glucose. From 1995, the authors
waited until the end of the paper to explain that the metabolism was being
carried out by the rodents gut bacteria, not by the rats themselves. No wonder
it was only one paper.
Just because we can’t metabolize L-sugars doesn’t mean that
we mammals are left out in the cold. Some sugars are used in the L-form even if
they aren’t broken down to make ATP. The most egregious example of this is a
hexose sugar called L-altrose. Why
is it different than some other exceptions here? Because altrose doesn’t even
occur in nature as a D-sugar; only the L-form has ever been found. It was first
isolated in 1987 from a bacterium called, Butyrvibrio
fibrisolvens, which is found in the GI tract of ruminate animals (cows and such).
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Ruminants are mammals that have more involved digestive
strategies. Ruminants have many types of GI bacteria to help
them break down tough plant material; it isn’t surprising that
some of them can use nonstandard carbohydrates in their
physiology. “Ruminating” is the act of re-chewing food that
has been partially softened by bacterial action in the first
compartment of the stomach, and then brought back to the
mouth as “cud.” I ruminate on ideas all the time, but I think I
will stop – I’m going to call it “further thought” from now on.
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It turns out that L-sugars are common in bacterial LPS. I
found examples from several different bugs, including L-quinvose (6-deoxy-L-
glucose), L-rhamnose, and L-fucose (6-deoxy–L- galactose).
When it comes to L-sugars, plants can get into the act as
well. Rhamnose (6-deoxy-L-mannose)
occurs in nature, and can be isolated from several plants of the genera Rhamnus and Uncaria, including Buckthorn, poison sumac, and many other plants.
Rhamnose from plants takes the form of a glycoside. There’s there word again, glyco-. A glycoside in general terms is
any molecule bound to a sugar. In plants, attaching sugars to create
glycosides is a common way to inactivate molecules so that they can be stored
for later use. When needed, the sugar residues of glycosides are cleaved away
by special enzymes and then the protein, enzyme, lipid, etc. becomes active.
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Digoxin
(or sometimes digitalis) are cardiac glycosides from
foxglove
plants. They are used to treat atrial rhythm or heart
failure
problems. First used by William Withering in 1785,
digitalis
is said to be the first of the modern day therapeutics.
But
it can kill you too, both the plants and the drugs. A nurse
was
sentenced to 18 life sentences after he was convicted of
killing
more than 40 patients with digoxin.
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Some evidence suggests that rhmanose and fucose can inhibit
the activation of the elastase enzyme in skin cells. Elastase is known to
increase in expression and activity as skin cells in culture divide several
times. Therefore, companies want you to believe that rhamnose will keep your
skin from looking old. Forget that keratinocytes in a petri dish bear as much resemblance
to your skin as Watchmen does to Hamlet.
That was a bit sarcastic, but the cosmetic industry is a pet
peeve of mine. And while I’m exposing my soul, I might as well admit to being a
bit of a speciesist. I like the exceptions best when they involve Homo sapiens, so the last exception for
today has to do with our own uses for a deoxy-L-sugar, fucose. I must admit that several uses of fucose apply to many
mammals, but being the speciesist that you know I am, I ignore them to focus on humans.
Fucose (6-deoxy–L-galactose) is crucial for the turning of an unloved spermatozoa and a lonely oocyte into very premature teenager. Both the
development and maturation of gamete cells and the development of the embryo
depend on the recognition and communication of surface molecules that include
fucose. But wait, there’s more.
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The
H antigen is linked to the red blood cell through a fucose
residue,
but not in the “h” antigen mutant. Because of this, it
is
not recognized for modification to the A or B antigen, and
the
typical H antigen is not there to prevent development of
the H antibody.
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However, not all is goodness and light when it comes to
fucose. Some folks have a mutation in their H antigen gene that prevents its
maturation to the A or B antigen. All cells would have the mutant H antigen,
called h. This is different from being type O (meaning not having any A or B
antigen, but still having the H antigen).
The hh or Oh blood type is called the Bombay type, and is very rare. Bombay individuals can donate blood
to anyone, regardless of blood type (because they do not express any antigen to
be attacked). However, because they make A, B, and H antibodies, they can
receive blood only from another
person with Bombay blood type. Since Bombay occurs about three times in a
million births – good luck with that search for blood.
Let’s tackle the nucleic acids and their exceptions starting next
week. By training I am a molecular biologist; I know an exceptional number of nucleic acid exceptions.
For
more information or classroom activities, see:
Bombay
blood type –
Glycosides
–
Racemization
–
http://journalofcosmology.com/SearchForLife108.html
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