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Purine nucleoside phosphorylase

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purine-nucleoside phosphorylase
purine-nucleoside phosphorylase. PDB 1rct.[1]
Identifiers
EC no.2.4.2.1
CAS no.9030-21-1
Databases
IntEnzIntEnz view
BRENDABRENDA entry
ExPASyNiceZyme view
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MetaCycmetabolic pathway
PRIAMprofile
PDB structuresRCSB PDB PDBe PDBsum
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NCBIproteins
Purine nucleoside phosphorylase
Identifiers
AliasesPurine_phosphorylaseIPR011268
External IDsGeneCards: [1]; OMA:- orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
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Purine nucleoside phosphorylase, PNP, PNPase or inosine phosphorylase (EC 2.4.2.1) is an enzyme that in humans is encoded by the NP gene.[2] It catalyzes the chemical reaction

purine nucleoside + phosphate purine + alpha-D-ribose 1-phosphate

Thus, the two substrates of this enzyme are a purine nucleoside and phosphate, whereas its products are a purine and alpha-D-ribose 1-phosphate.

Nomenclature

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This enzyme belongs to the family of glycosyltransferases, specifically the pentosyltransferases. The systematic name of this enzyme class is purine-nucleoside:phosphate ribosyltransferase.

Other names in common use include:

  • inosine phosphorylase
  • PNPase
  • PUNPI
  • PUNPII
  • inosine-guanosine phosphorylase
  • nucleotide phosphatase
  • purine deoxynucleoside phosphorylase
  • purine deoxyribonucleoside phosphorylase
  • purine nucleoside phosphorylase
  • purine ribonucleoside phosphorylas

This enzyme participates in 3 metabolic pathways: purine metabolism, pyrimidine metabolism, and nicotinate and nicotinamide metabolism.

Function

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Purine nucleoside phosphorylase is an enzyme involved in purine metabolism. PNP metabolizes inosine into hypoxanthine and guanosine into guanine, in each case creating ribose phosphate. Note: adenosine is first metabolized to inosine via the enzyme adenosine deaminase.[3]

One of the reaction catalyzed by purine nucleoside phosphorylase in purine metabolism

Nucleoside phosphorylase is an enzyme which cleaves a nucleoside by phosphorylating the ribose to produce a nucleobase and ribose 1 phosphate. It is one enzyme of the nucleotide salvage pathways. These pathways allow the cell to produce nucleotide monophosphates when the de novo synthesis pathway has been interrupted or is non-existent (as is the case in the brain). Often the de novo pathway is interrupted as a result of chemotherapy drugs such as methotrexate or aminopterin.

All salvage pathway enzymes require a high energy phosphate donor such as ATP or PRPP.

Adenosine uses the enzyme adenosine kinase, which is a very important enzyme in the cell. Attempts are being made to develop an inhibitor for the enzyme for use in cancer chemotherapy.

Enzyme regulation

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This protein may use the morpheein model of allosteric regulation.[4]

Clinical significance

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PNPase, together with adenosine deaminase (ADA), serves a key role in purine catabolism, referred to as the salvage pathway. Mutations in ADA lead to an accumulation of (d)ATP, which inhibits ribonucleotide reductase, leading to a deficiency in (d)CTPs and (d)TTPs, which, in turn, induces apoptosis in T-lymphocytes and B-lymphocytes, leading to severe combined immunodeficiency (SCID).[citation needed]

PNP-deficient patients will have an immunodeficiency problem. It affects only T-cells; B-cells are unaffected by the deficiency.

See also

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References

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  1. ^ Canduri F, dos Santos DM, Silva RG, Mendes MA, Basso LA, Palma MS, de Azevedo WF, Santos DS (Jan 2004). "Structures of human purine nucleoside phosphorylase complexed with inosine and ddI". Biochemical and Biophysical Research Communications. 313 (4): 907–14. doi:10.1016/j.bbrc.2003.11.179. PMID 14706628.
  2. ^ "Entrez Gene: NP nucleoside phosphorylase".
  3. ^ Kaplan USMLE Biochemistry Review
  4. ^ Selwood T, Jaffe EK (Mar 2012). "Dynamic dissociating homo-oligomers and the control of protein function". Archives of Biochemistry and Biophysics. 519 (2): 131–43. doi:10.1016/j.abb.2011.11.020. PMC 3298769. PMID 22182754.

Further reading

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