Guanine is an important nitrogen base and has a central role in nucleic acid metabolism in the organism. It can be synthesized in the body from amino acids. However, due to the high energy expenditure of this reaction, its recovery often occurs via the salvage pathway.
What is guanine?
Guanine is one of the five nitrogenous bases that are instrumental in the construction of DNA and RNA. It is also a basic component of other physiologically important molecules such as guanisine triphosphate (GTP). Guanine represents a purine base whose basic chemical structure consists of a heterocyclic aromatic ring of six atoms and an attached ring of five. In the body, it usually occurs as a mononucleotide with ribose or deoxyribose and a phosphate residue. Along with ATP, the mononucleotide GTP is an energy store in the context of energy metabolism. In the double helix of DNA, guanine is linked to the complementary nitrogen base cytosine via three hydrogen bonds. Since the formation of free guanine is very energy-intensive, it is recovered in the body from nucleic acids by cleavage (salvage pathway) and used again in the form of a mononucleotide for nucleic acid synthesis. In the body, it is degraded to uric acid. Guanine is a slightly yellowish solid with a melting point of 365 degrees. It melts under decomposition. It is insoluble in water, but can be dissolved in acids and alkalis.
Function, effect and tasks
Guanine is a component of nucleic acids and various nucleotides and nucleosides. As an important nucleic base, it is one of the central molecules of all organisms. Together with the other three nucleic bases adenine, cytosine and thymine, it forms the genetic code. Like these, it is glycosidically bound to the sugar deoxyribose in DNA. Three consecutive nucleic bases encode one amino acid each as a so-called codon. Several codons thus encode a protein as a chain of consecutive amino acids. The genetic code is stored in the DNA. Within the double helix of the DNA there is a complementary chain with the respective complementary nucleic bases. It is linked to the codonogenic chain by hydrogen bonding and is responsible for the stability of the genetic information. Within RNA, guanine plays an important role in protein synthesis, along with the other nucleic bases. Important intermediates in metabolism are also the nucleosides guanisine and deoxyguanisine. Furthermore, the nucleotides guanisimonophosphate (GMP), guanisine diphosphate (GDP) and guanisine triphosphate (GTP) are also responsible for energy metabolism in addition to ATP and ADP. DNA nucleotides also occur in metabolism as intermediate compounds.
Formation, occurrence, properties, and optimal values
Guanine possesses central importance in the metabolism of all organisms. Since it is a component of nucleic acids, it also occurs freely as an intermediate in metabolism. In the human organism, it can be synthesized from amino acids. However, biosynthesis is very energy-intensive. Therefore, it is recovered from nucleic acids via the Salvage Pathway in the form of a nucleotide. In the salvage pathway, free purine bases such as adenine, guanine, and hypoxanthine are excised from existing nucleic acid and, in turn, new mononucleotides are formed. This process is much more energy efficient than the new synthesis of guanine and its mononucleotide. The mononucleotide is reused for nucleic acid synthesis. Thus, the salvage pathway represents a recycling process. During the degradation of guanine, uric acid is formed via the intermediate product xanthine. Purine degradation in the body is the major source of uric acid. In birds, reptiles, and bats, guanine is an important excretory product for nitrogen, along with uric acid. Because this pasty product contains little water and is also poorly utilized for energy production, it is excreted directly, especially by birds and bats. Because its excretion reduces the total mass, the flying ability of these animals is improved. The excreted guanine forms the so-called guano, especially on calcareous soils after weathering. Guano is a very valuable fertilizer rich in phosphorus and nitrogen.
Diseases and disorders
When guanine metabolism is disturbed, health problems can occur. For example, when the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is defective, the salvage pathway is disrupted.The so-called Lesch-Nyhan syndrome develops from this. In this disease, guanine mononucleotides are not sufficiently recovered from the nucleic acids. Instead, there is increased degradation of guanine. Large amounts of uric acid are formed in the body. Therefore, this disease is also called hyperuricemia syndrome. In severe cases, autoaggression, cognitive impairment and even external aggression occur. Patients frequently injure themselves. Mostly boys are affected because the autosomal recessive disorder is caused by a gene mutation on the X chromosome. In girls, both X chromosomes would have to be affected by the mutation, but this is rare. If Lesch-Nyhan syndrome is left untreated, children die in infancy. Guanine degradation can be inhibited by the use of drugs and a special diet. The symptoms can thus be partially alleviated. Unfortunately, however, Lesch-Nyhan syndrome cannot be treated causally. Hyperuricemias can also occur in association with other diseases or other genetic defects. Primary hyperuricemias are one percent genetic and 99 percent due to decreased uric acid excretion by the kidneys. There are also secondary forms of hyperuricemia. For example, diseases associated with increased cell decay, such as leukemias or certain blood diseases, can lead to increased production of purines and thus uric acid. Medications or alcoholism can also lead to disorders of purine metabolism. As a result of increased uric acid concentrations, gout attacks can occur due to uric acid precipitation in the joints. Included in treatment is a low-purine diet and, therefore, a low-guanine diet.
