Guanosine Triphosphate: Function & Diseases

Guanosine triphosphate, as a nucleoside triphosphate, is an important energy store in the organism along with adenosine triphosphate. It mainly provides energy during anabolic processes. Furthermore, it activates many biomolecules.

What is guanosine triphosphate?

Guanosine triphosphate (GTP) represents a nucleoside triphosphate composed of the nucleotide base guanine, the sugar ribose, and three phosphate residues linked by anhydride bonds. Guanine is glycosidically bonded to ribose, and ribose in turn is bonded to the triple phosphate residue via an esterification. The anhydride bond of the third phosphate group to the second phosphate group is very energetic. Upon cleavage of this phosphate group, GTP, as with the analogous compound adenosine triphosphate (ATP), provides much energy for certain reactions and signal transduction. GTP is formed either by single phosphorylation from GDP (guanosine diphoshate) or via triple phosphorylation of guanosine. In this process, the phosphate groups originate from ATP as well as from transfer reactions within the citric acid cycle. The starting material guanosine is a nucleoside of guanine and ribose. GTP is converted to GMP (guanosine monophosphate) with the release of two phosphate groups. As a nucleotide, this compound is a building block of ribonucleic acid. In its isolated state outside the body, GTP is a colorless solid. In the body, it performs many functions as an energy transporter and phosphate supplier.

Function, action, and roles

In addition to the more familiar ATP, GTP is also responsible for many energy-transferring reactions. Many cellular metabolic reactions can only take place with the help of energy transfer by guanosine triphosphate. As with ATP, the binding of the third phosphate residue to the second phosphate residue is very energy-rich and comparable to its energy content. However, GTP catalyzes different metabolic pathways than ATP. GTP obtains its energy within the citric acid cycle from the breakdown of carbohydrates and fats. It is also possible to transfer energy from ATP to GDP under the transfer of a phosphate group. This results in the formation of ADP and GTP. Guanosine triphosphate activates many compounds and metabolic pathways. For example, it is responsible for the activation of G-proteins. G proteins are proteins that can bind GTP. This enables them to transmit signals via G-protein-associated receptors. These are signals for olfaction, vision or blood pressure regulation. GTP stimulates signal transduction within the cell by assisting in the transmission of important signaling substances or by initiating a signaling cascade by stimulating the G molecules under energy transfer. Furthermore, protein biosynthesis cannot occur without GTP. Chain elongation of the polypeptide chain takes place with the absorption of energy derived from the conversion of GTP to GDP. The transport of many substances, including membrane proteins, to membranes is also significantly regulated by GTP. Furthermore, GTP also regenerates ADP back to ATP under the transfer of a phosphate residue. It also activates the sugars mannose and fucose, forming ADP-mannose and ADP-fucose. An important function of GTP continues to be its involvement in the assembly of RNA and DNA. GTP is also indispensable for the transport of substances between the cell nucleus and cytoplasm. It should also be mentioned that GTP is the starting material for the formation of cyclic GMP (cGMP). The compound cGMP is a signal molecule and is responsible, among other things, for visual signal transduction. In the kidney and intestine, it controls ion transport. It sends the signal for the dilation of blood vessels and bronchial tubes. Finally, it is thought to be involved in the development of brain function.

Formation, occurrence, properties, and optimal levels

Guanosine triphosphate is found in all cells of the organism. It is indispensable as an energy store, phosphate group transmitter, and building block for the construction of nucleic acids. In the context of metabolism, it is produced from guanosine, guanosine monophosphate (GMP) or guanosine diphosphate (GDP). GMP is a nucleotide of ribonucleic acid. It can also be recovered from this. However, new synthesis in the organism is also possible. The binding of further phosphate groups to the phosphate group esterified on the ribose is always possible only with an expenditure of energy.In particular, the anhydridic bonding of the third phosphate group to the second involves a high energy input, because electrostatic repulsive forces build up which are distributed over the entire molecule. Tensions are formed within the molecule, which are transferred to the corresponding target molecule when it comes into contact with it, releasing a phosphate group. Conformational changes occur in the target molecule, which trigger the corresponding reactions or signals.

Diseases and disorders

When signal transduction in the cell does not occur properly, a variety of diseases can result. Of great importance for signal transduction in the context of the function of GTP are the G proteins. G proteins represent a heterogeneous group of proteins that can transmit signals by binding to GTP. This triggers a signaling cascade that is also responsible for neurotransmitters and hormones taking effect by docking to G protein-associated receptors. Mutations in G proteins or their associated receptors often disrupt signal transduction and are the cause of certain diseases. For example, fibrous dysplasia or Albrigh bone dystrophy (pseudohypoparathyroidism) is caused by mutation of a G protein. In this disease, there is resistance to parathyroid hormone. That is, the body does not respond to this hormone. Parathyroid hormone is responsible for calcium metabolism and bone formation. The bone-building disorder leads to myxomas of the skeletal muscles or functional disorders of the heart, pancreas, liver and thyroid gland. In acromegaly, on the other hand, there is resistance to Growth Hormone Releasing Hormone, so that growth hormone is released uncontrollably, causing increased growth of limbs and internal organs.