Purine is an organic compound and a heteroaromatic with four nitrogen atoms, becomes the finished purine nucleus by five additional carbon atoms and forms the basic body of the entire substance group of purines. The latter are important building blocks of nucleic acids and at the same time the stores of hereditary information. Purines are present in all cells, are ingested with food, but are also formed by the body itself, mainly during the breakdown of body cells. Animal foods in particular contain a lot of purine, e.g. in fish and meat, especially in the skin and offal. Free purine has not yet been discovered in nature.
What is purine?
The name of purines is derived from Latin. “Purus” stands for purity and “acidum uricum” is uric acid. Purines are therefore the pure basic structure of uric acid. They were first synthesized at the end of the 19th century by the chemist Emil Fischer, who is also the founder of organic chemistry and was awarded the Nobel Prize for Chemistry in 1902 for his work. Purines have a heterocyclic aromatic ring structure consisting of six atoms. They are the molecular building blocks of the DNA bases guanine and adenine. These are derived from purine of hydrogen atoms and therefore also belong to the purine bases. When these bases are linked to the C-1 atom of ribose, the nucleosides guanosine and adenosine are formed. An exothermic reaction with phosphate then produces nucleotides. These are the building blocks of many physiological molecules. Purine nucleotides are not only energy suppliers, but also building blocks of co-enzymes such as NAD, FAD or NADP. At the same time, they are the signal transducers and the intermediates of synthesis pathways and metabolic processes. In this process, they form a network and are synthesized under different conditions. This is not done as free molecules, but as nucleotides. On the other hand, they are degraded to uric acid. Purines bind to receptors in the cell membrane in the same way.
Function, effect, and tasks
Although the human organism forms purine itself, it does not excrete it directly. Through a multistep process, purine is primarily broken down to uric acid. Both the uric acid itself and all intermediate products are then collected in the kidney, where they are excreted. First, the entire purine nucleus forms. More precisely, the carrier molecule ribose-5-phosphate is phosphorylated and thus activated. This is done by cleavage from the pyrophosphate to provide energy for the next steps. In addition to synthesis to the purine base, purine also serves for the biosynthesis of NAD and for purine recycling. Once cleavage from the pyrophosphate has occurred, glutamine is transferred to the phosphoribose residue. PRA occurs and is catalyzed by amidophosphoribosyltransferase. This enzyme regulates substrate flow in metabolism. After this reaction, the second of the four nitrogen atoms is incorporated. The third is supplied by glutamine and used by phosphoribosylformylglycinamidine synthase. After water splitting, AIR, i.e. 5-aminoimidazolribonucleotide, is formed. This is carboxylated to CAIR. The aspartate cycle starting thereupon incorporates the fourth nitrogen atom into the purine nucleus, condensation with aspartate occurs, and fumarate is cleaved off. Through a formyl residue, the reaction is catalyzed by phosphoribosylaminoimidazole carboxamide formyltransferase. The pyrimidine ring is closed with cleavage by water. The purine nucleus is complete.
Formation, occurrence, properties, and optimal values
In medicine, purine derivatives are drugs used as antimetabolites to suppress, for example, azathioprine in the immune system. Biosynthesis with purine can be inhibited as a blockade of folate metabolism, e.g., with methotrexate. This results in a deficiency of the DNA building blocks, and cell proliferation is hindered, especially in proliferation-prone tissues. This in turn is used to treat tumor cells in cancer therapy and autoimmune diseases. Allopurinol is used against gout and prevents purine degradation to uric acid. Purine n-oxides, in turn, have a carcinogenic effect.
Diseases and disorders
Since purines are broken down by the organism as uric acid, disorders can occur if the body no longer manages this process properly, the breakdown is reduced, and the uric acid is not sufficiently excreted. Uric acid crystals then form, which in turn lead to gout. Particularly due to diet, the incidence of gout has increased over time.In the past, it was still a disease that only occurred in socially higher classes. Half of the purines are produced by the body and half are absorbed through food. The consequence of gout attacks is then a disturbance of kidney function, which in turn can lead to painful kidney stones. Gout is treated with medication, but is often also accompanied by dietary measures and a special diet that is low in purines, i.e. avoids offal or types of fish such as herring, anchovies or oil sardines. As soon as the uric acid level rises, the concentration in the blood becomes too high, uric acid crystals form, which are needle-shaped and are deposited in the kidneys, cartilage, tendon sheaths, skin and joints. The deposits cause inflammation. Uric acid levels should not exceed 6.5 mg/dl in men, and should be somewhat lower in women. High uric acid levels in the blood do not always have to lead to gout; genetic predisposition and other ailments are also triggers. One of these is Lesch-Nyhan syndrome. This is a hereditary disease based on the disturbed metabolism of purines and occurs due to an overload of the body by uric acid. It is a rather rare metabolic disease inherited recessively with the X chromosome, which has a deficiency of hypoxanthine-guanine phosphoribosyltransferase. The absence of this important enzyme in the organism causes the increased urinary level and central nervous system disorders.
