MadSci Network: Biochemistry

Re: Are GTP,CTP,TTP used in everyday energy transfers ?

Area: Biochemistry
Posted By: Michael Onken, WashU
Date: Sun Nov 23 20:19:57 1997
Area of science: Biochemistry
ID: 878660835.Bc

To clarify the second part of your question first, ATP, GTP, CTP, and UTP are used in RNA synthesis, while dATP, dGTP, dCTP, and dTTP are used for DNA replication (click on the above link for more). This is an important point, because dATP has no role outside of DNA, while ATP is, as you pointed out, essential for many enzymatic processes. It is also worth noting that there is no TTP: there are UTP and dTTP. To answer your main question, let's look at each nucleotide separately.

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.

A couple final points regarding nucleotides: If you noticed, 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. Also, since the majority of enzymatic reactions in the cell use nucleotides in one form or another, and since many forms of RNA have enzymatic activities, many scientists have postulated that life began with RNA and free nucleotides, which together carried out most of the functions now attributed to proteins.

Molecular Biology of the Cell, Alberts, et al., Garland Publishing, Inc., 1989 (2nd Ed.).

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