22nd April 20:03
NMN as a nucleotide
NAD is an abbreviation for nicotinamide adenine dinucleotide. Discard
the adenosine and you get NMN - nicotinamide mononucleotide.
NAD is perhaps the most important redox cofactor in modern biochemistry.
But we here want to speculate on NMN's possible role as a nucleotide in
Notice that the "base" portion of NMN is a planar aromatic heterocycle
that can form stacking interactions with a double helix. Moreover,
ISTM that NMN can form WC-pairing hydrogen bonds in a double helix.
Think of the nicotinamide as a substitute for a purine. There can
be two hydrogen bonds formed between the carboxamide of NMN and
a pyrimidine on the other strand. Is NMN a spoof of adenine or guanine?
Well, that depends on the conformation of the carboxamide. One
conformer would act like adenine; the other like guanine. (Two thirds
like guanine, anyways.)
Of course there is a big problem with this. The linkage between base
and sugar in the oxidized form of NMN is through a quaternized
nitrogen. So the geometry is wrong for a double helix. The reduced
form of NMN is worse - the ring is now a quinone, so it is not even
planar. So we can't form extended helical structures using NMN as
a nucleotide. But we can perhaps use it in places where the helix
is disrupted - perhaps in pseudo-knots, etc.
The notion of using conformers of carboxamide for WC bonding is too
cute to throw out, though. Perhaps we should be considering carboxamide
derivatives of pyrimidines rather than of pyridines. It would be neat
if we could come up with a plausible base material that acts like a
purine if "syn" and like a pyrimidine if "anti". It would be REALLY
neat if this base material could also serve as a redox cofactor,
switching from planar to quinone form. If redox chemistry could serve
as kind of motor causing mechanical deformation of a helix, then there
are a variety of ways this could be used by early metabolism.
Incidentally, I want to call attention to one factoid that may or
may not be significant. Ligation of broken strands in a double helix
requires a source of phosphate energy, of course. But this ancient
process doesn't use nucleotide triphosphates as the energy source.
Instead it uses the linkage between the two nucleotides in NAD as the
energy source! Odd, and probably significant, but the solution to
this puzzle eludes me.
Of course, several of the other dinucleotide cofactors are also capable
of forming WC base pairs. But in these cases, it is not clear whether
this should be taken as evidence that they DID form such base pairs
in the RNA world, or whether it is simply a relic of the formation
of these cofactors from guanine.
23rd April 16:22
NMN as a nucleotide
I'm not sure what I was thinking when I wrote this. The quaternized,
positively-charged nitrogen in NMN distorts the helix very little.
For some reason, I was assuming that the 1' carbon of the sugar would
not be in the plane of the aromatic ring. But, of course it would be.
It only leaves that plane in the reduced form of NMN.
Sorry about that!