[1] Salvage pathways for purine nucleotides synthesis (recycling)
Most cells have an active turnover of many of their nucleic acids (particularly some types of RNA) which, through degradative processes, result in the release of adenine, guanine and hypoxanthine. These free purines are reconverted to their corresponding nucleotides through salvage pathway. The de novo synthesis of purines requires a substantial investment of ATP. Purine salvage pathways provide a more economical means of generating purines.
Free purine bases, derived from the turnover of nucleotides or from the diet, can be attached to PRPP to form purine nucleoside monophosphates, in a reaction analogous to the formation of orotidyalte. Two salvage enzymes with different specificities recover purine bases. Adenine phosphoribosyltransferase (APRT) catalyzes the formation of adenylate (AMP):
Free purine bases, derived from the turnover of nucleotides or from the diet, can be attached to PRPP to form purine nucleoside monophosphates, in a reaction analogous to the formation of orotidyalte. Two salvage enzymes with different specificities recover purine bases. Adenine phosphoribosyltransferase (APRT) catalyzes the formation of adenylate (AMP):
Adenine + PRPP ---> Adenylate + PPi
Whereas hypoxanthine-guanine phosphoribosyltransferase (HGPRT) catalyzes the formation of guanylate (GMP) as well as inosinate (inosine monophosphate, IMP), a precursor of gunylate and adenylate:
Guanine + PRPP ---> Guanylate + PPi
Hypoxanthine + PRPP ---> Inosinate + PPi
Pyrimidine bases can be recovered from the breakdown products of DNA and RNA by the use of salvage pathways. In these pathways, a preformed base is reincorporated into a nucleotide. Let us consider salvage for the pyrimidine base thymine. Thymine is found in DNA and base-pairs with adenine in the DNA double helix. Thymine released from degraded DNA is salvaged in two steps. First, thymine is converted into the nucleoside thymidine by thymidine phosphorylase.
Thymine + deoxyribose-1-phosphate ----> Thymidine + Pi
Thymidine is then converted into a nucleotide by thymidine kinase.
Thymidine + ATP ----> TMP + ADP
[Biochemistry, Berg, Stryer, 8th Edition, 2015]
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