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Purine nucleoside phosphorylase

Class of enzymes From Wikipedia, the free encyclopedia

Purine nucleoside phosphorylase
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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
Quick Facts Identifiers, EC no. ...
Quick Facts Identifiers, Aliases ...

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.

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Nomenclature

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.

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Function

Summarize
Perspective

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]

Thumb
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.

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Enzyme regulation

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

Clinical significance

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.

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See also

References

Further reading

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