Guanosine is the nucleoside of the purine base guanine and is formed by the addition of the simple sugar ribose. If deoxyribose, rather than ribose, is attached, it is deoxyguanosine. Guanosine is a component of the helices and double helices of RNA. The analogue deoxyguanosine is part of DNA. Guanosine, as a guanosine triphosphate (GTP) with three phosphate groups attached, is an important energy store and donor of phosphate groups within the citrate cycle in cell mitochondria.
What is guanosine?
Guanosine is the nucleoside of the purine base guanine. It is formed by the addition of a ribose group via an N-glycosidic bond. In the analogue deoxyguanosine, the attached pentose consists of the deoxyribose group. Guanosine and deoxyguanosine are components of the single and double helices of RNA and DNA. The complementary base is formed in each case by the pyrimidine base cytosine or its nucleoside cytidine and deoxycytidine, with which guanosine is connected as a base pair with a triple hydrogen bridge. With additional phosphate groups attached, guanosine forms an important functional part of the so-called citrate cycle within the respiratory chain as guanosine diphosphate (GDP) and as guanosine triphosphate (GTP). This is a chain of catalytically controlled processes within the energy metabolism that takes place in the mitochondria of the cells. GTP serves here as an energy store and phosphate group donor. Under the action of a specific enzyme, GTP can be converted into the cyclic guanosine monophosphate, which plays a special role in signal transduction within the cell, by splitting off two phosphate groups. In a slightly modified form as so-called Ran-GTP, GTP performs transport tasks for the necessary transport of substances between the cell nucleus and cytosol, overcoming the cell membrane in each case.
Function, action, and tasks
The double and single helices of the genetic material DNA and RNA consist of a concatenation of only four different nucleic bases, of which the bases guanine and adenine are based on the purine backbone, which consists of a five- and a six-membered ring. The two bases cytosine and thymine embody pyrimidine bases with an aromatic six-membered ring. The nucleic base uracil, which is almost identical to thymine and occupies the position of thymine in RNA, must be seen as an exception. However, the long chains of helices do not consist of unmodified nucleic acids, but of their nucleotides. The nucleic bases are transformed into riboses or deoxyriboses by the addition of one ribose group (RNA) or one deoxyribose group (DNA), respectively, and into the corresponding nucleotide by the addition of one or more phosphate groups. In the case of guanine, this is guanosine monophosphate or deoxyguanosine monophosphate, which is incorporated as a link in the long-chain helices of RNA and DNA. As a component of DNA and RNA, guanosine – like the other nucleotides – has no active role but encodes, via copies of the DNA strand, the corresponding proteins that are synthesized in the cell. An active role is played by guanosine in the form of GTP and GDP in the citrate cycle within the respiratory chain as a phosphate group donor. In the modified form of guanosine monophosphate, the nucleotide also assumes an active role and provides a messenger for intracellular signal transport, which is particularly important for anabolic processes in protein synthesis. In the form of Ran-GTP, the nucleotide provides specialized transport vehicles for substance transport from the nucleus through the nuclear membrane into the cytosol.
Formation, occurrence, properties, and optimal levels
The chemical molecular formula of guanosine is C10H13N5O5, indicating that the nucleoside is composed entirely of carbon, hydrogen, nitrogen, and oxygen. These are molecules that are available in virtually unlimited quantities on Earth. Rare trace elements or minerals are not part of guanosine. Guanosine is found – mostly in the form of the nucleotide of the same name – with few exceptions in all human cells as a component of DNA and RNA, as well as in the mitochondria and cytosol of the cells. The body is able to synthesize guanosine within the purine metabolism in a very complex process. However, the preferred way to obtain guanosine is via the salvage pathway process. Higher-value compounds containing nucleic bases or nucleotides are degraded enzymatically-catalytically in such a way that nucleosides such as guanosine can be recycled.For the body, this has the advantage that the biochemical degradation processes are less complex and thus less prone to error, and that less energy, i.e. less ATP and less GTP consumption, takes place. The complexity and rate at which guanosine and its mono-, di-, and triphosphates are involved in catalytic reactions do not allow a direct statement about an optimal concentration in blood serum.
Diseases and disorders
The multiple metabolic processes in which guanosine is involved, along with other nucleosides and especially in the phosphorylated form as a nucleotide, dictate that dysfunction may occur at some points in metabolism. It is mainly genetic defects that can result in the absence of certain enzymes or inhibition of their bioactivity. A known X-linked genetic defect leads to Lesch-Nyhan syndrome. The syndrome causes a dysfunction in the salvage pathway of purine metabolism, so that the body must increasingly follow the anabolic pathway of new synthesis. The recessively inherited genetic defect leads to a loss of function of hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Despite increased new synthesis, a deficiency of guanosine or its bioactive derivatives develops. This is associated with excessive uric acid production, which causes corresponding concomitant symptoms such as the formation of urinary and renal stones. The permanently elevated uric acid level can lead to precipitation of uric acid crystals in the tissue and cause painful attacks of gout. Even more serious in this regard are the neurological disorders, including a tendency to self-mutilation.
