International Max Planck Research School for Terrestrial Microbiology
I
think there could be some other processes that use alternative energy
sources waiting to be found. We have very recently identified a
CTP-dependent mechanism for bacterial chromosome segregation.
Interestingly, our protein is related to the eukaryotic sulfiredoxin
which uses ATP.
However,
ATP and GTP based regulation seems to be more widespread, perhaps
learning more about alternative nucleotide regulation will help to
answer your question
I do not believe in "By Chance Theory" at all, It was used only where people cannot come up with a good reasons of explanation.
Please
look at and compare the chemical structures of adenine and ATP vs
guanine and GTP and also consider the evolution of adenine and guanine
molecules at many billion years ago on our Earth. At that time and
before that, the oxygen level on Earth was below 0.1% as compared to 20%
nowaday. Therefore, adenine was far earlier than guanine appearred on
Earth by billions of years on early Earth. It is because, adenine has no
oxygen atom in its structue, whereas guanine has 1 oxygen atom in its
structure. Therefore, the amount of adenine molecule was then
(pre-historic of our Earth) and is now (oxygen 20% and nitrogen
50%) far more than that of guanine.
When
more oxygen and phosphorus were formed billions years later, then ATP
and GTP were formed; but their amounts were a matter of several orders
of magnitude different between the two, that ATP is a lot more than GTP.
Your
question is interesting but not easy to answer. Probably an
evolutionarily 'young' enzyme used ATP as a co-factor and not
another NTP by chance. With time orthologues of this hypothetical enzyme
arose through gene duplication, for instance, so the use of ATP
became more widespread. Probably ATP was the first NTP that could be
synthesized by early cells...?
I
think the chemical structure of adenine involving in the synthesis of
ATP in the mitochondrial ATP synthase pump is more favourable than that
of the quanine. This ATP synthesis is coupled with that of the oxidative
phosphorylation and respiration functions of the mitochondria, which we
learnt from biochemistry. But GTP, CTP and TTP syntheses were seldomly
coupled with mitochondria as we learnt.
Wow
what an interesting teleological question? It is a tough questions to
ponder as well. I had many times wondered about it as well. Here are
some thoughts:
1.
Perhaps a chance factor? Although it is easier to make pyrimidine
ring/pyrimidines just with 2 or three components (Aspartate, HCO3, ATP)
and Glutamine.
Now let us ask: Why Purine (Adenine)?
2.
One possible factor may be inosine synthesis involves Glycine. As a
simple aa perhaps there was more of Glycine in the prebiotic era that
favored inosine<adenine<guanine synthesis. For making
Inosine/adenine you need: 1C-folate, Glycine, Glutamate (can be easily
obtaied by transamination of alpha-KG), Aspartate (can be easily
obtained by transamination of OAA).
3. Now remember for making pyrimidine you need ATP not GTP.
4. In addition many cofactor seems to have this handle that is made of Adenosine (NAD, FAD, CoA, PAPS etc...)
5.
With all these put together it was easy to synthesize Adenosine/ATP
first because of the available prebiotic ingredients such as Glycine,
CO2/HCO3, Folate, Glutamine and Aspartate. In all it might be just
Glycine which started the whole sequence of events.
My thoughts lean more with the "chance" theory argument, presenting my points:
1)
I agree with both Christian and Venkatachalam in that a Chance event
might have been the first choice! I strongly tend to support the
hypothesis that the molecule came about first before we were able to
evolve the proteins that synthesize it (therefore I tend not to go by
Zhou's hypothesis where metabolism precedes small molecule evolution).
This makes chance event a much simpler iteration towards ATP....
though if iteration is simply the answer, we cannot fathom as to
why a single ring cytosine or thymine couldn't be used as against a
double ring ATP/GTP (there's more than meets the eye).
2)
Especially if we look at the prebiotic soup and about its constituents,
I like Venkatachalam's suggestion which is that Glycine could've
started the whole process via via intermediates that led to ATP and
other nucleosides.
3)
I think the theme of Gene Duplication (which Christian suggests as
well), seems to be the best explanation as we observe time and again....
that a model once built (by chance) is repeated by biology over and
over again (several examples of Domains being repeatedly used in varying
combinations and so on), and thats how it came about to be the dominant
energy storage of the cell.
4)
GTP did evolve as well eventually.... by alternate use of the
enzymes/processes by which ATP came to be, and followed suite and hence
is used in fewer enzyme processes. (energentically ATP and GTP may not
be very different?)
5) Lastly, The simpler model is to evolve TWO separate energy molecules:
ONE as a powerhouse (ATP) and
SECOND as a sensor (GTP) and
other minor ones like cAMP/cGMP and ddTTP and such.
This
model gives better modulatory control over pathways, rather than have
to intermingle and make it extremely confusing chemistry to figure
out when ATP would be a sensor versus a powerhouse.
I do not believe in "By Chance Theory" at all, It was used only where people cannot come up with a good reasons of explanation.
Please
look at and compare the chemical structures of adenine and ATP vs
guanine and GTP and also consider the evolution of adenine and guanine
molecules at many billion years ago on our Earth. At that time and
before that, the oxygen level on Earth was below 0.1% as compared to 20%
nowaday. Therefore, adenine was far earlier than guanine appearred on
Earth by billions of years on early Earth. It is because, adenine has no
oxygen atom in its structue, whereas guanine has 1 oxygen atom in its
structure. Therefore, the amount of adenine molecule was then
(pre-historic of our Earth) and is now (oxygen 20% and nitrogen
50%) far more than that of guanine.
When
more oxygen and phosphorus were formed billions years later, then ATP
and GTP were formed; but their amounts were a matter of several orders
of magnitude different between the two, that ATP is a lot more than GTP.
Very
interesting question indeed. I am considering two folds, namely, the
prokaryotic and eukaryotic cells. The "power house", the
mitochondria, of Eukaryotic cells was proposed to come from
the endosymbiosis of an early prokaryotic cell. The mitochondrion is
responsible for generating majority of the ATPs. The endosymbiosis
process of such prokaryotic cell is for sure a probabilistic event,
which depends on the metabolism of the symbiotic prokaryote. For
prokaryote energy metabolism at the time before eukaryogenesis, due
to the diversity of ecological adaptations of prokaryotes there are
possibly both types existing, but the majority is ATP using type. So the
question finally rests at: why at the time before eukaryogenesis the
majority type is ATP using? As some other comments mentioned, is it due
to the earth environment at the time?
@MH
Zhou Didn't the earliest forms of life (the RNA world) use RNA,
which contains all four base pairs, not just adenine? So how could
adenine have come before guanine?
I
think now we should think out the problem from the protein perspective.
RNA came first: Which means during early RNA world we already had ATP,
GTP, CTP and UTP to make RNA.
Now the question is: Why did we selectively chose ATP for energetic purposes?
As I had suggested earlier the ATP binding protein fold was easier/most suited to have been made during the course evolution.
For
e.g. tRNA synthetase I from bacteria uses ATP and splits it between
alpha-beta position to yield ~7.6 kcals of energy. In addition the
Ubiquitous pyrophosphatase would cleave the PPi into 2Pi releasing
additional energy.
Then came the protein fold that split ATP between beta-gamma position.
So
I am tempted to say that ATP for energetics and GTP for signaling (came
about due to shear chance of protein folding). After all with the trial
and error, some sort of evolutionary consensus came about which at the
end resulted in ATP for energetics and GTP for signaling.
CTP,
TTP and UTP being monocyclic was not selected because of loose amino
acid interaction that is required for binding and would perhaps incur
non-specificity and poor binding.
I
guess we have to give more importance to the time factor, trial and
error, chance event, reaching out on consensus and eventually reaching
the ultimate universal perfection. Once the perfection is made, that
motif is common among all the organisms from archaea to eukaryotes.
Uracil
has two oxygen atoms in its chemical structure, therefore, its
evolution had to occur a lot later than Adenine, which has no oxygen
atom at all. And the amount of Adenine molecule was the most abundant
one amongst U, G, T, and C, during the earliest period of Life
Evolution. I am kind of agree with the idea that pyrimidine has only one
ring in its structure and is not specific enough as compared to
2-rings-purine to develop signalling bonding abilities.
I
don't know when, how or why one is chosen over the other but it's good
that we have two different NTPs, one for energy and one for signalling.
If we solely depended on ATP/GTP for everything that goes on in our
cells, we would run out of it quickly I think. So it's good that we have
separate stocks and one can be converted into the other when
necessary..
It
is interesting to note from Filiz Korkmaz above, that the
evolution of ATP was related to energy first before life development in
the earliest time at 4.2 billion years ago, while the evolution of GTP
was later because it needed oxygen atom in the GTP molecule (remember,
the oxygen level in the atmosphere was very low at that earlier time!).
That means the signalling function of cells was developed much later
than the energy production in the mitochondria.
Both
ATP and GTP act as both energy currency and signal molecules (i.e.
there are signal pathways that form cyclic AMP to carry signals, and
signal pathways that form cyclic GMP, etc.). Structurally, these two
molecules perform each other's functions in many different
circumstances.
As
to why ATP ended up heavily favored as an energy currency as opposed to
GTP, which is more favored in common signaling pathways, I can only
offer two observations that might be factors:
The
body needs to have some way to use energy for signalling and to use
energy for other purposes. Since GTP and ATP are both present at the
same time, it makes sense to specialize one for one task and the other
for the other.
In
DNA and RNA, Adenine forms only two hydrogen bonds with the pyrimidines
T and U whereas Guanine forms three with C. Therefore, if you simply
had to choose which nucleotide to use for bulk energy transactions
between A and G, it would make sense to choose A because there is
slightly less energy required to separate it from its binding partner in
structures (which would be a benefit when you want to isolate it and
use it as an energy molecule).
Mayo Foundation for Medical Education and Research
ATP
- is Bitcoin! ATP is considered as cellular currency for a long time. I
realized that ATP is Bitcoin - cellular cryptocurrency, along with
other NTPs (GTP, CTP, UTP, TTP), few others cryptocurrencies. And it
uses same network and blockchain technology, this technology is used in
nature for millions of years! By comparing to biological blockchain new
features and possibilities of cryptocurreny can be revealed. 😃
It's a very nice discussion. Each expert's own perspective provides
the closest results to the truth. The behavior of the molecules, a
little bit of chance, enough time, and the result is incredibly
molecular organization in this catastrophic environment. Very complex
structural and functional relationship networks. I think ATP had started
a step ahead in this area.
Clearly the relative solubility of the nucleobases adenine and guanine is relevant! For life to focus on adenylates as the primary energy transducers, the solubility of adenine has to be tractable. Guanine is practically water-insoluble and so is a dubious choice for a base constituent of the central metabolic pool.
This
is soo interesting..But then why GTP is utilized and not just ATP in
Kreb's cycle,protein synthesis,gluconeogenesis,signal transduction in
G-proteins etc..
Nirali,
ATP can vary over larger magnitudes of concentration than GTP. So the
inference is probably because, if a model where metabolically highly
variant energy sources (ATP) versus a less variant signalling source
(GTP), if separated in utility, provides a more robust/responsive system
for
regulation. I must say that this inference is more speculative.
Mayo Foundation for Medical Education and Research
That
different NTPs involved in different processes - something is to do
with energy distribution and thermodynamic independence. Say, GTP/GDP
ratio controls protein synthesis independent of changes in ATP/ADP
ratio. Energy of GTP hydrolysis (deltaG GTP) apparently is higher than
ATP, such energy is required for efficient protein synthesis. In
signaling systems there are GTP-sensitive G-proteins as well as
independent ATP-sensitive - A-proteins (e.g. K-ATP channel). Similarly
with other NTPs - they provide energy to specific processes which can be
regulated independently and have thermodynamics sovereignty.
Number of phosphotransfer enzymes regulate delivery of specific NTPs to
distant process. Presence of phosphotransfer enzymes in the vicinity of
signaling or synthetic enzymes guarantee rapid regeneration of spent
NTPs maintaining high local level. It is known that NDPK regulates
GDP-GTP conversion and G-protein signaling. In cancer cells energy
distribution is uncontrollable, as they shift to glycolytic metabolism,
which can spread ATP everywhere in the cell including nucleus, and have
deranged phosphotransfer system.
I
agree with Petras: different pathways use different energy carriers
(not only nucleotides, but also for example pyrophosphate and
phosphoenolpyruvate). One could imagine that these pathways developed
independently, and came together when the modern cell arose from more
primitive predecesors by endosymbiont formation and horizontal gene
transfer. The possibility to regulate these pathways independently is
then an added bonus. Of course, that is speculation as we weren't there
to observe 4 billion years ago.
Wow this is a very informative debate about the favourable use of ATP over other NTPs.
Here I want to say two things:
First
the free atmospheric oxygen has no role to give a preference to ATP
then GTP. Because we need to keep in mind that oxygen atom of Inosine,
the precursor of Guanine and Adenine can come from CO2 or dissolved CO2
(HCO3) or can be contributed by H2O.
Second,
if we think about biosignaling here also ATP out competed other NTP in
the form of cAMP, which can sense the status of energy in the cell and
at the same time, can play a significant role in signal transduction.
But other molecule including Ca2+ , cGMP, IP3 have a complimentary role
for signalling.
Eukaryotic
cells are not internally homogeneous, but are compartmentalized into
cytoplasmic and nuclear ground substances and the numerous organelles
embedded therein. Because of spatial heterogeneity, a comprehensive
understanding of the cell's metabolism requires not only data on the
rates of synthesis and utilization of adenosine triphosphate, b...
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and H...
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