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Text 1079, 85 rader
Skriven 2004-12-18 06:15:00 av Perplexed In Peoria (1:278/230)
Ärende: Re: purine/vitamin b9 par
=================================



"IRR" <iotarhorho@REMOV3hotmail.com> wrote in message
news:cpvp7r$1m3u$1@darwin.ediacara.org...
>
> "Perplexed in Peoria" <jimmenegay@sbcglobal.net> wrote in message
> news:cppsj2$2qad$1@darwin.ediacara.org...
> >
> > "IRR" <iotarhorho@REMOV3hotmail.com> wrote in message
> > news:cpok29$2ekk$1@darwin.ediacara.org...
> > [ ... Which came first - THF or purines? ...]
> >> Thanks for the reply.  A more generic overview is here:
> >> http://web.indstate.edu/thcme/mwking/nucleotide-metabolism.html
> >> (the section on purine biosynthesis), or a mechanistic view here:
> >> http://www.chem.qmul.ac.uk/iubmb/enzyme/reaction/misc/purine1.html
> >> N10-formyl-THF is apparently the source of the formyl group (giving THF
> >> as
> >> product) in "ring building" in both this early step pathway and again in
> >> a
> >> later antepenultimate step towards IMP biosynthesis.  But my
> >> understanding
> >> of THF biosynthesis is that the purine GTP is explicitly used in pterin
> >> construction, which are essential THF precursors.  I'm embarrassed that I
> >> can't figure this out -- there ought to be a simple solution to this
> >> apparent paradox?
> >
> > Biochemistry is filled with "loops" like this.  There is no "paradox".
> > Only a chicken-egg puzzle in the context of OOL.  The generic solution
> > to this kind of puzzle is to assume that the current pathways are not
> > the primordial pathways.  In this case, it is pretty clear that guanine
> > was being produced by some pathway not involving THF long before the
> > modern pathway was "invented".  All we need is some donor of a formyl
> > group - THF is a convenient source of formyl groups today, but some
> > other source may have been available in early life.  Or, a completely
> > different pathway for purine production was used.  Some people even
> > claim that purines were produced in quantity by non-biological processes.
>
> Thanks so much for the response.  So I now understand how this circumvents
> my (pseudo) paradox, but this of course requires that these biosynthetic
> precursors have been sustained parent-to-progeny since that primordial
> pathway.  Is that an acceptable formulation from a biologist's perspective?
> It seems a bit fragile to maintain those sorts of contingencies, i.e. rather
> than maintaining some pathway to go from CO2 directly to THF without
> requiring THF-derived intermediates, but I suppose if you're pinning a
> pathway to some essential intermediate, using a DNA base is probably a safe
> bet for its ubiquity and for the prebiotic routes of synthesis you allude
> to.  Is that thinking correct?

I'm not sure I understand the questions.  Are you asking whether nature is
taking a risk in requiring that at least one molecule of THF (or perhaps GTP)
must be passed on to each daughter cell?  If so, then I would say that the risk
is minimal compared to the other risks the daughters face.

> I'd be interested to know of other examples of such loops, sounds like a
> potentially interesting lot from an OOL/evolution perspective.

The biggest and most complex loop, of course, is that modern metabolism makes
essential use of protein enzymes to make more protein enzymes.  The simplest
"loop"
that I know of is in the commonest pathway for the formation of high energy
bonds.  The following reaction takes place at the F0F1 complex coupled with
the discharge of a proton gradient:
(1)  ADP + phosphate -> ATP.
So where did the ADP come from?
(2)  AMP + ATP <--> 2 ADP
ADP is thus its own precursor.  If somehow, all ATP and ADP were removed from
the cell, and only AMP remained, then high energy phosphate production would
stop.  But throw in one ADP molecule, and the process is off and running.  In
fact, the number of ADP molecules will grow exponentially - until the
exponentially growing ATP population begins to be siphoned off to other tasks
besides regenerating ADP.

A loop similar in complexity to the THF/purine one that started this discussion
can be seen in the Calvin cycle.  Five ribose molecules, after a long series of
reactions, become 6 ribose molecules.  But also notice that the cofactors
that are involved - NADH and ATP - themselves include ribose as an essential
component.
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