Nucleotide salvage

A salvage pathway is a pathway in which nucleotides (purine and pyrimidine) are synthesized from intermediates in the degradative pathway for nucleotides.

Salvage pathways are used to recover bases and nucleosides that are formed during degradation of RNA and DNA. This is important in some organs because some tissues cannot undergo de novo synthesis.

The salvaged bases and nucleosides can then be converted back into nucleotides.

Substrates

The salvage pathway requires distinct substrates:

Pyrimidines

Uridine phosphorylase or pyrimidine-nucleoside phosphorylase adds ribose 1-phosphate to the free base uracil, forming uridine. Uridine kinase (aka uridine–cytidine kinase) can then phosphorylate this nucleoside into uridine monophosphate (UMP). UMP/CMP kinase (EC 2.7.4.14) can phosphorylate UMP into uridine diphosphate, which nucleoside diphosphate kinase can phosphorylate into uridine triphosphate.

Thymidine phosphorylase or pyrimidine-nucleoside phosphorylase adds 2-deoxy-alpha-D-ribose 1-phosphate to thymine, forming thymidine. Thymidine kinase can then phosphorylate this compound into thymidine monophosphate (TMP). Thymidylate kinase can phosphorylate TMP into thymidine diphosphate, which nucleoside diphosphate kinase can phosphorylate into thymidine triphosphate.

The nucleosides cytidine and deoxycytidine can be salvaged along the uracil pathway by cytidine deaminase, which converts them to uridine and deoxyuridine, respectively. Alternatively, uridine–cytidine kinase can phosphorylate them into cytidine monophosphate (CMP) or deoxycytidine monophosphate (dCMP). UMP/CMP kinase can phosphorylate (d)CMP into cytidine diphosphate or deoxycytidine diphosphate, which nucleoside diphosphate kinase can phosphorylate into cytidine triphosphate or deoxycytidine triphosphate.

The salvage of pyrimidine ribonucleotides.

Purines

Phosphoribosyltransferases add activated ribose-5-phosphate (Phosphoribosyl pyrophosphate, PRPP) to bases, creating nucleoside monophosphates. There are two types of phosphoribosyltransferases: adenine phosphoribosyltransferase (APRT) and hypoxanthine-guanine phosphoribosyltransferase (HGPRT). It is an important enzyme in Purine pathway metabolism.[1] It is also involved in Lesch-Nyhan syndrome associated with a deficiency of HGPRT.

Nucleobase Enzyme Nucleotide
hypoxanthine hypoxanthine/guanine phosphoribosyl transferase (HGPRT) IMP
guanine hypoxanthine/guanine phosphoribosyl transferase (HGPRT) GMP
adenine adenine phosphoribosyltransferase (APRT) AMP

References

  1. ↑ Ansari MY, Equbal A, Dikhit MR, Mansuri R, Rana S, Ali V, Sahoo GC, Das P (Nov 2015). "Establishment of Correlation between In-Silico &In-Vitro Test Analysis against Leishmania HGPRT to inhibitors". International Journal of Biological Macromolecules. doi:10.1016/j.ijbiomac.2015.11.051. PMID 26616453.
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