In the salvage pathway, a new biomolecule is synthesized from the degradation products of a biomolecule. The salvage pathway is also known as the salvage pathway and is, in a sense, a form of recycling within metabolism.
What is the salvage pathway?
Salvage pathway refers firstly to the general form of this recycling within metabolism and secondly to the metabolic pathway of purine nucleotides. Purine nucleotides are the basic chemical building blocks of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). In putine nucleotide salvage, mononucleotides are formed from the purine bases guanine, adenine and hypoxanthine. With 90%, this metabolic pathway is the main metabolic pathway for free purines. The remainder is degraded to uric acid. Above all, the salvage pathway offers numerous advantages over the de novo biosynthesis of purine mononucleotides. For example, it is significantly more energy efficient.
Anatomy and structure
The synthesis of bicyclic purine bases is costly to the body. Therefore, they are degraded to simple bases and then reused. In the salvage pathway, various intermediates of the degradation of mononucleotides, nucleosides, polynucleotides, or nucleic acid bases are used in assembly reactions instead of being completely degraded. The salvage pathway reaction can save useful and valuable metabolic intermediates, so-called metabolites, from disposal. These metabolites therefore do not have to be produced again. This process thus spares the cell a high energy consumption. In the salvage pathway, a ribose phosphate from phosphoribosyl pyrophosphate (PRPP) is transferred to a free purine base. The nucleotide is thus formed by splitting off pyrophosphate. The enzymes required for this are activated by the phosphoribosyl pyrophosphate and inhibited by the end products. From the purine base adenine, together with (PRPP) and by means of the enzyme adenine phosphoribosyltransferase (APRT), adenosine monophosphate (AMP) is formed. Guanine, in conjunction with PRPP and the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT), becomes the nucleotide guanosine monophosphate (GMP). Hypoxanthine is converted to the nucleotide inosine monophosphate (IMP) with PRPP and the enzyme hypoxanthine-guanine phosphoribosyltransferase. Other enzymes involved in the salvage pathway are nucleoside phosphorylases, nucleoside kinases, and nucleotide kinases. 90% of purines are first converted to nucleotides and then reused for the synthesis of nucleic acids through transformations. 10% of purines are degraded to uric acid and excreted by the kidney.
Function and tasks
The salvage pathway occurs in almost all cells of the body, as purines are also degraded in almost all cells of the body. Purines belong to the group of heterocycles and, along with pyrimidines, are the major building blocks of nucleic acids. Purines are formed using the salvage pathway itself. They are present in all cells that have a cell nucleus. Foods of animal origin, especially offal and skin, contain many purines. The purines that are not recycled by the salvage pathway are broken down to uric acid and excreted by the kidneys. There are no blood values for the salvage pathway, but there are for uric acid. In men, blood uric acid levels are normally between 3.4 and 7.0 mg / 100ml. In women, uric acid levels should be between 2.4 and 5.7 mg /l.
Diseases
If there is a defect in the salvage pathway, purines can no longer be recycled. Thus, significantly more purines are broken down, resulting in increased uric acid as well. The kidney is no longer able to excrete the uric acid completely, resulting in hyperuricemia. Hyperuricemia is defined as an increase in the uric acid level in the blood. By definition, hyperuricemia is present at a uric acid level of 6.5 mg / dl. The threshold value applies equally to both sexes. An increase in uric acid levels due to a disturbance of the salvage pathway is also referred to as primary hyperuricemia. About 1% of all hyperuricemias are caused by uric acid overproduction due to a disorder in purine metabolism. The majority of primary hyperuricemias are based on decreased uric acid excretion in the kidney. To distinguish whether the elevated urine levels are based on decreased excretion or increased uric acid production, uric acid clearance must be determined.To calculate uric acid clearance, uric acid excretion in 24-hour urine collection and serum uric acid are determined. In most cases, hyperuricemia remains asymptomatic. In the case of massive hyperuricemia, an acute gout attack occurs. Here, the crystallized salts of uric acid are deposited in the joints. This leads to inflammation in the affected joints with overheating, pain and severe redness. The metatarsophalangeal joint of the big toe, the ankle joint and the knee joint are particularly frequently affected. If gout persists for a long time, tissue remodeling occurs. The cartilage in the joints thickens and so-called gout tophi develop. A genetic defect that leads to hyperuricemia is Lesch-Nyhan syndrome. The disease is inherited in an X-linked recessive manner and results in a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Since the enzyme is involved in the purine metabolism of the purine bases hypoxanthine and guanine, more purines are produced for degradation. The result is a sharp increase in uric acid. The disease is inherited X-linked. Therefore, Lesch-Nyhan syndrome almost exclusively affects men. The first symptoms appear about ten months after birth. The children show a conspicuous leg position in combination with a lack of movement and developmental delays. The first sign is often increased urine retention in the diaper. In severe cases, there is also self-injury such as lip and finger biting and impaired thinking skills. Affected children may also behave aggressively toward their parents, siblings, friends, or caregivers.
