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A salvage pathway is a pathway in which a biological product is produced from intermediates in the degradative pathway of its own or a similar substance. The term often refers to nucleotide salvage in particular, in which nucleotides ( purine and pyrimidine ) are synthesized from intermediates in their degradative pathway.
It is not the committed step to purine synthesis because PRPP is also used in pyrimidine synthesis and salvage pathways. The first committed step is the reaction of PRPP, glutamine and water to 5'-phosphoribosylamine (PRA), glutamate , and pyrophosphate - catalyzed by amidophosphoribosyltransferase , which is activated by PRPP and inhibited by ...
Modulating the pyrimidine metabolism pharmacologically has therapeutical uses, and could implement in cancer treatment. [10] Pyrimidine synthesis inhibitors are used in active moderate to severe rheumatoid arthritis and psoriatic arthritis, as well as in multiple sclerosis.
It is a biochemical intermediate in the formation of purine nucleotides via inosine-5-monophosphate, as well as in pyrimidine nucleotide formation. Hence it is a building block for DNA and RNA. [1] [2] [3] The vitamins thiamine [4] and cobalamin, [5] and the amino acid tryptophan also contain fragments derived from PRPP. [6]
Pyrimidine degradation ultimately ends in the formation of ammonium, water, and carbon dioxide. The ammonium can then enter the urea cycle which occurs in the cytosol and the mitochondria of cells. [5] Pyrimidine bases can also be salvaged. For example, the uracil base can be combined with ribose-1-phosphate to create uridine monophosphate or UMP.
HGPRTase functions primarily to salvage purines from degraded DNA to reintroduce into purine synthetic pathways. In this role, it catalyzes the reaction between guanine and phosphoribosyl pyrophosphate (PRPP) to form GMP, or between hypoxanthine and phosphoribosyl pyrophosphate (PRPP) to form inosine monophosphate.
The purine nucleotide cycle occurs in the cytosol (intracellular fluid) of the sarcoplasm of skeletal muscle, and in the myocyte's cytosolic compartment of the cytoplasm of cardiac and smooth muscle. The cycle occurs when ATP reservoirs run low (ADP > ATP), such as strenuous exercise, fasting or starvation. [5] [9]
CTP (cytidine triphosphate) synthetase catalyzes the last committed step in pyrimidine nucleotide biosynthesis: [3] ATP + UTP + glutamine → ADP + P i + CTP + glutamate . It is the rate-limiting enzyme for the synthesis of cytosine nucleotides from both the de novo and uridine salvage pathways.