The guanosine triphosphate o Guanosine triphosphate (GTP) is one of the many phosphate nucleotides capable of storing free energy easily usable for multiple biological functions.
Unlike other related phosphate nucleotides, which usually provide the necessary energy to execute a great 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.
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 systems in vitro What in vivo.
The energy contained in their bonds, especially between 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..
Article index
As is true for adenine nucleotides (ATP, ADP and AMP), GTP has three indisputable elements as its basic structure:
-A heterocyclic guanine (purine) ring
-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..
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 that make up DNA and other molecules.
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 pathway 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
There are many cellular metabolic pathways capable of producing GTP other than the biosynthetic pathway de novo. These usually do it through the transfer of phosphate groups, coming from different sources, towards the precursors GMP and GDP..
GTP, as a phosphate nucleotide 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.
The GTP has many functions that have been demonstrated through experiments in vitro in "cell-free" systems. From these experiments it has been possible to demonstrate that it actively participates in:
-Protein synthesis in eukaryotes (for both initiation and elongation of peptides)
-Stimulation of protein glycosylation
-The synthesis of ribosomal RNA in prokaryotes and eukaryotes
-Phospholipid synthesis, particularly during diacylglycerol synthesis
Other experiments, but in cellular systems or in vivo have verified the participation of the GTP in processes such as:
-Sporulation and activation of spores of different classes of microorganisms, prokaryotes and eukaryotes
-Synthesis of ribosomal RNA in eukaryotes
-Among other.
It has also been proposed that oncogenic progress from normal cells to cancer cells involves loss of control over cell growth and proliferation, involving many GTP-binding proteins and protein kinases with specific GTP-dependent activity..
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).
Yet No Comments