With the help of purine synthesis, all living organisms produce purines. Purine is, among other things, a component of the DNA bases guanine and adenine as well as of the important energy carrier ATP.
What is purine synthesis?
With the help of purine synthesis, all living things make purines. Purine is, among other things, a component of the DNA bases guanine and adenine and of the important energy carrier ATP. Purine synthesis is a biochemical process at the end of which purines are formed. Purines are organic compounds that occur in all living organisms. Purines are formed from the basic substance α-D-ribose-5-phosphate. The human cell converts the substance in several steps. Enzymes catalyze this process and assist in the conversion from one intermediate to the next. First, an enzyme converts α-D-ribose-5-phosphate to α-D-5-phosphoribosyl-1-pyrophosphate (PRPP) by expanding the molecule. Then follows the conversion of PRPP and glutamine into 5-phosphoribosylamine and glutamate. Subsequently, the body can no longer use the substances for the synthesis of other products, but only for purine synthesis. The addition of glycine creates a glycine amide ribonucleotide, which an enzyme transforms to a formylglycine amide ribonucleotide and then converts to phosphoribosyl formylglycine amidine and glutamic acid. Finally, inosine monophosphate (IMP) is formed via the intermediates 5-aminoimidazole ribonucleotide, 5-aminoimodazole-4-carboxylate ribonucleotide, SAICAR, AICAR and FAICAR. Cells can directly use IMP to make adenosine, guanine, and xanthosine. Purines do not exist as free molecules, but are always linked to other molecules in the form of nucleotides. The finished purine molecule consists of carbon dioxide, glycine, twice 10-formyltetrahydrofolic acid, glutamine, and aspartic acid.
Function and task
Part of the genetic information stored in deoxyribonucleic acid (DNA) consists of purines. DNA is made up of building blocks called nucleotides. These are composed of a sugar molecule (deoxyribose), a phosphoric acid and one of four bases. The bases adenine and guanine are purine bases: Their backbone is formed by a purine, to which other molecules bind. In addition, purine is a building block of adenosine triphosphate (ATP). This is the primary energy carrier in the human organism. In the form of ATP, energy is stored chemically and is available for numerous tasks. Muscles use ATP for movement as well as some synthesis processes and other processes. In the muscles, ATP also has the effect of a plasticizer: it ensures that the filaments of the muscles can separate from each other. The lack of ATP after death therefore leads to rigor mortis. To release the bound energy, cells and organelles split ATP into adenosine diphosphate and adenosine monophosphate. The cleavage releases approximately 32 kJ/mol. Furthermore, ATP serves to transmit signals. Within cells, it assumes a function in the regulation of metabolism. For example, it serves as a cosubstrate of kinases, which include insulin-stimulated protein kinase, which plays a role in the context of blood glucose. Outside cells, ATP serves as an agonist at purinergic receptors and helps transmit signals to nerve cells. ATP appears in signal transduction in the context of blood flow regulation and the inflammatory response, among others.
Diseases and ailments
Purine synthesis is a complex biochemical process in which errors can easily occur. In order for purine to be formed, specialized enzymes must convert the various substances step by step. Mutations can result in these enzymes not being coded correctly. The genetic material contains information about how the cells must synthesize the enzymes. Enzymes are made of protein, which in turn is composed of long chains of amino acids. Each amino acid must be in the right place for the enzyme to take the right form and function correctly. Errors can occur not only in the production of enzymes, but already in the genetic code. Mutations ensure that the stored information leads to faulty or incomplete amino acid chains. Such mutations can also affect the enzymes involved in purine synthesis. The resulting disorders fall into the category of metabolic diseases and are hereditary. A mutation in the PRPS1 gene, for example, causes a disorder in purine synthesis.PRPS1 encodes the enzyme ribose phosphate diphosphokinase. The mutation causes the enzyme to be overactive. Through various processes, this overactivity promotes the risk of gout. Gout (uricopathy) is a disease that occurs in episodes. Chronic gout develops after several acute outbreaks. The disease destroys the joints; changes in the hands and feet are often particularly visible. Pain in the joints, inflammation and fever are also among the symptoms of gout. In addition, deformities of the joints, reduced performance, kidney stones and kidney failure may manifest in the long term. However, defective purine synthesis can manifest itself in more than just gout. Another mutation on the PRPS1 gene causes a reduction in the activity of the enzyme ribose phosphate diphosphokinase. As a result, Rosenberg-Chutorian syndrome occurs. This mutation is also a possible cause of a certain form of deafness. Other genes also encode the enzymes of purine synthesis. The ADSL gene is also one of them. Mutations in the ADSL gene lead to a deficiency of adenylosuccinate lyase. This deficiency is a rare hereditary disease and is inherited in an autosomal recessive manner. The disease manifests itself already in newborns, but may also appear in childhood. The disease manifests itself rather unspecifically, for example in mental retardation, epilepsy and behavioral disorders similar to autism. Mutations in the ATIC gene can also disrupt purine synthesis. This section of genetic information scrambles the bifunctional purine synthesis protein, leading to the development of AICA ribosiduria. The literature documents only one case with intelligence reduction, congenital blindness, and shape changes in the knees, elbows, and shoulders.
