The guanosine triphosphate or guanosine triphosphate (GTP) is one of many nucleotides capable of storing phosphate free energy readily usable for multiple biological functions.
Unlike other related phosphate nucleotides, which usually provide the necessary energy to execute a wide variety of processes in different cellular contexts, some authors have shown that nucleotides such as GTP, UTP (uridine triphosphate) and CTP (cytidine triphosphate) provide energy mainly in anabolic processes.
Chemical structure of Guanosine Triphosphate or GTP (Source: Cacycle, via Wikimedia Commons)
In this sense, Atkinson (1977) suggests that GTP has functions that involve the activation of many anabolic processes through different mechanisms, which has been demonstrated in both in vitro and in vivo systems.
The energy contained in their bonds, especially between the phosphate groups, is used to drive some cellular processes involved especially in synthesis. Examples of this are protein synthesis, DNA replication and RNA transcription, microtubule synthesis, etc.
Structure
As is true for adenine nucleotides (ATP, ADP and AMP), GTP has three indisputable elements as its basic structure:
-A heterocyclic guanine ring (purine)
-A five-carbon base sugar, ribose (furan ring) and
-Three phosphate groups attached
The first phosphate group of GTP is attached to the 5 'carbon of the ribose sugar and the guanine residue is attached to this molecule through the 1' carbon of the ribofuranose ring.
In biochemical terms, this molecule is a guanosine 5'-triphosphate, better described as a purine triphosphate or, with its chemical name, 9-β-D-ribofuranosylguanine-5'-triphosphate.
Synthesis
GTP can be synthesized de novo in many eukaryotes from inosinic acid (inosine 5'-monophosphate, IMP), one of the ribonucleotides used for the synthesis of purines, which are one of the two types of nitrogenous bases of which DNA and other molecules are made up.
This compound, inosinic acid, is an important branch point not only for the synthesis of purines, but also for the synthesis of the nucleotides phosphate ATP and GTP.
The synthesis of guanosine phosphate nucleotides (GMP, GDP and GTP: guanosine mono-, di- and triphosphate, respectively) begins with the NAD + -dependent hydroxylation of the purine ring of IMP, forming the intermediate compound xanthosine monophosphate (XMP).
This reaction is catalyzed by an enzyme known as IMP dehydrogenase, which is allosterically regulated by GMP.
An amide group is then transferred to the XMP thus produced (glutamine and ATP dependent reaction) through the action of the enzyme XMP aminase, where a molecule of guanosine monophosphate or GMP is produced.
Since the most active nucleotides are, in general, triphosphate nucleotides, there are enzymes responsible for the transfer of phosphate groups to GMP molecules that are generated in the route just described.
These enzymes are specific ATP-dependent kinases (kinases) known as guanylate kinases and nucleoside diphosphokinases.
In the reaction catalyzed by guanylate cyclases, ATP acts as a phosphate donor for the conversion of GMP to GDP and ATP:
GMP + ATP → GDP + ADP
Guanine diphosphate nucleotide (GDP) is subsequently used as a substrate for a nucleoside diphosphokinase, which also uses ATP as a phosphate donor for the conversion of GDP to GTP:
GDP + ATP → GTP + ADP
Synthesis by other routes
There are many cellular metabolic pathways capable of producing GTP other than the de novo biosynthetic pathway. These usually do it through the transfer of phosphate groups, coming from different sources, towards the GMP and GDP precursors.
Features
GTP, as a nucleotide phosphate analogous to ATP, has countless functions at the cellular level:
-Participates in the growth of microtubules, which are hollow tubes composed of a protein known as “tubulin” whose polymers have the ability to hydrolyze GTP, which is essential for its elongation or growth.
-It is an essential factor for G proteins or GTP-binding proteins, which function as mediators in various signal transduction processes that are related, in turn, to cyclic AMP and its signaling cascades.
These signaling processes result in the communication of the cell with its environment and of its internal organelles with each other, and are especially important for carrying out the instructions encoded in hormones and other important factors in mammals.
An example of these signaling pathways of great importance for the cell is the regulation of the enzyme adenylate cyclase through its interaction with a G protein.
Features
GTP has many functions that have been demonstrated through in vitro experiments in "cell-free" systems. From these experiments it has been possible to demonstrate that it actively participates in:
-Protein synthesis in eukaryotes (both for the initiation and elongation of peptides)
-Stimulation of protein glycosylation
-The synthesis of ribosomal RNA in prokaryotes and eukaryotes
-The synthesis of phospholipids, particularly during the synthesis of diacylglycerol
Certain functions
Other experiments, but in cellular or in vivo systems have proven the participation of GTP in processes such as:
-Sporulation and activation of the spores of different classes of microorganisms, prokaryotes and eukaryotes
-Synthesis of ribosomal RNA in eukaryotes
-Among other.
It has also been proposed that the oncogenic progression from normal cells to cancer cells involves loss of control over cell growth and proliferation, in which many GTP-binding proteins and protein kinases with specific GTP-dependent activity participate.
GTP also has stimulating effects on the importation of proteins into the mitochondrial matrix, which is directly related to its hydrolysis (more than 90% of mitochondrial proteins are synthesized by ribosomes in the cytosol).
References
- Alberts, B., Dennis, B., Hopkin, K., Johnson, A., Lewis, J., Raff, M.,… Walter, P. (2004). Essential Cell Biology. Abingdon: Garland Science, Taylor & Francis Group.
- Mathews, C., van Holde, K., & Ahern, K. (2000). Biochemistry (3rd ed.). San Francisco, California: Pearson.
- Pall, M. (1985). GTP: A Central Regulator of Cellular Anabolism. In B. Horecker & E. Stadtman (Eds.), Current Topics in Cellular Regulation (Vol. 25, p. 183). Academic Press, Inc.
- Rawn, JD (1998). Biochemistry. Burlington, Massachusetts: Neil Patterson Publishers.
- Sepuri, NB V, Schu, N., & Pain, D. (1998). GTP Hydrolysis Is Essential for Protein Import into the Mitochondrial Matrix. The Journal of Biological Chemistry, 273 (3), 1420–1424.