ATP vs. GTP/CTP - Why does nature use ATP for energy coupling? (Apr/03/2006 )
I am preparing my final exam and just asked myself a simple question which turned out to be not so simple...
Why does nature use (in most cases) ATP to couple energy into reactions? Why not GTP or CTP?
(Actually, GTP is used for some processes, but I don't know any reactions that use CTP)
The amount of energy they provide upon hydrolysis into ADP/GDP/CDP and Pyrophosphate is the same.
So there should be some evolutionary advantage, which is the reason to favor ATP...
Thank you in advance!
i don't have a strick answer, but i realized once that GTP gives some energy in reactions and also serves as cofactor for G proteins.
And A and G are purines. So probably purines are better holded than pyrimidines...
But why A vs G ?...
ATP: Adenosine is the all-purpose nucleotide, assuming several roles in almost every pathway in the cell. Adenosine can be used as a source of energy, acting alone as ATP or combined with other nucleotides, like niacin in NAD or riboflavin in FAD. Enzymes which directly hydrolyse ATP into ADP and phosphate are called ATPases. ATPases are found throughout the cell performing a wide variety of functions from pumping ions across the membrane to running all of the cytoplasmic motors that shuttle material around the cell and drive cilia, flagella, and muscles. Adenosine is also used extensively by the cell as a source of phosphates for modifying proteins - several proteins require phosphorylation to be activated or inactivated, and this is used by the cell to control which enzymes are on or off. The enzymes which phosphorylate other proteins are called kinases and all require ATP to function. There are several other functions of Adenosine that I won't go into here to save space.
GTP: Guanosine is used similarly to Adenosine, but in fewer roles. There are a very few instances in which GTP is used as a phosphate donor or an energy source, most notable of which is Tubulin, which must hydrolyze GTP to GDP to form the microtubules of the cytoskeleton. There are several other GTPase enzymes in the cell, however most of these enzymes are not used for their enzymatic properties, but rather are used to transmit signals throughout the cell. G-proteins are a specific class of GTPases which use their binding to GTP to interact with other enzymes to activate the cell. Many hormones and neurotransmitters have receptors that use G-proteins to transmit their signals to the rest of the cell. There are several other GTPases, including the Ras and Rab families of small GTPases, that are all also used to transmit signals and to control other intercellular traffic through their binding to GTP.
UTP: Uridine is used for a different purpose from the purine nucleotides. The most common example of this is in glycogen synthesis. Many cells in the body (especially in the liver) store glucose (sugar) in the form of glycogen, a complex starch composed of long, branching chains of glucose molecules. To enhance this reaction, free glucose molecules prepared for addition by reacting them with UTP to produce UDP-glucose and free phosphate. This makes the glucose molecules more reactive, since the glucose-phosphate bond in UDP-glucose is a high energy bond. As the UDP-glucose is added to glycogen, the UDP is released, and the energy is used to attach the glucose to the glycogen molecule. In fact, Uridine is used for UDP-glucose, UDP-galactose, UDP-mannose, etc., the building blocks of numerous carbohydrates that are essential for many cellular functions.
CTP: Cytidine is used very similarly to Uridine, however instead of sugars, CTP is used with fats. CDP-diacylglycerol, CDP-ethanolamine, and CDP-choline are the building blocks of the phospholipids that make up the cell membrane. Since all cells require intact membranes to survive, this is an exceedingly important cellular function.
The purine nucleotides have a wide range of uses, while the pyrimidines act more as handles than anything else. This is probably due to the more reactive nature of the purine rings, which makes ATP especially an ideal co-enzyme.
I doubt there's an energy reason -- as you noted, there's an equal amount of energy in the phospate bonds of other nucleotides.
It's likely that this is an evolutionary preference -- an early enzyme worked with ATP, and through evolution, other orthologous genes arose through gene duplication and genetic drift. Nature doesn't waste time reinventing the wheel, so since the early ancestor used ATP, so do the bulk of its orthologs.
As the cell became more complex, the ability to separate energy-producing enzymatic reactions on the basis of the nucleotide providing the bonds becomes beneficial, and thus orthologs which preferencially use GTP, for example, were selected for.
The inter-related nature of these genes can not only be seen at the sequence level, but also in their catalytic abilities -- most of these enzymes show a strong preference for "their" NTP, but will also catalyse other nucleotide triphosphates as well, at a greatly reduced rate.
A similar example can be found regarding the isocitrate dehydrogenases -- some of which reduce NAD (to make ATP, BTW) and others of which reduce NADP (in the synthesis of certain amino acids).
See the article here.
BTW, I suppose it is equally likely that ATP is the most wide-spread energy-providing NTP used by the cell because it was the first one that could be synthesized by the cell, or that it is the one most easily synthesized, or some other reasons (likely a combination of reasons)...