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In order to replace the obligatory loss of purines during tissue nucleic acid turnover and to meet the requirement for purine accretion for growth, the animals use two anabolic processes: purine biosynthesis de novo and purine salvage.
Purine can be synthesized from basic precursors: glycine, glutamine, aspartate, formate, and CO2. On completion of the purine ring, inosinic acid is produced, which is then converted to either adenosine nucleotide(AMP) or guanosine nucleotides(GMP).
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Preformed purines, either from the degradation of tissue nucleic acids or from the dietary nucleic acids, in the form of nucleosides and freebases, can be spared from degradation and reutilised for the synthesis of new nucleotides. The process is often called 'purine salvage'. It is an ongoing process, even when there is no exogenous purine supply. In man, during of the turnover of tissue nucleic acids, over 90% of the degraded nucleotides are salvaged. The enzymes involved in the purine salvage processes are widely distributed in the body and may be important in providing purine ribonucleotides in tissues such as the brain that have a high turnover of purines but a limited capacity for their de novo synthesis.
The formation of purine nucleotides for free bases is catalysed by the enzyme phosphoribosyltransferases (PRTase), which include adenine-PRTase (Ad-PRTase) and hypoxanthine-guanine PRTase (Hx-PRTase):
It should be pointed out that Hx-PRTase can also act on xanthine to form XMP (Xanthosine 5'-phosphate) but this reaction is very slow since xanthine has poor affinity to this enzyme at a comparable concentration, hypoxanthine could react at a rate 1700 times higher than xanthine would do. It is likely that xanthine would principally proceed towards the degradation process to produce uric acid. Uric acid, however, is not salvageable, and is further oxidised to allantoin by uricase (EC 1.7.3.3).
The phosphorylation of purine nucleosides to form nucleotides by nucleoside kinase is an alternative pathway of purine salvage. However, so far this has been documented in animal system only for adenosine. The presence of adenosine kinase ( EC. 2.7.7.20) was reported. The conversion of other purine nucleosides to the nucleotides possibly depends on the prior cleavage to their free bases which would then subsequently serve as the substrates of the purine PRTases.
The cost of synthesis of purines by the salvage processes is far lower than that for the de novo process: formation of one mole of purine mononucleotide formed by salvage requires 2 ATP whereas adenylic or guanylic acid synthesis requires 7 or 8 ATP, respectively.
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