Purine nucleoside phosphorylase

Not to be confused with polynucleotide phosphorylase.

purine-nucleoside phosphorylase
File:1rct.png purine-nucleoside phosphorylase. PDB 1rct.
Identifiers
EC number	2.4.2.1
CAS number	Template:CAS
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search PMC articles PubMed articles NCBI proteins

Purine nucleoside phosphorylase also known as PNPase and inosine phosphorylase is an enzyme that in humans is encoded by the NP gene.

In enzymology, a purine-nucleoside phosphorylase (EC 2.4.2.1) is an enzyme that catalyzes the chemical reaction

purine nucleoside + phosphate $\rightleftharpoons$ purine + alpha-D-ribose 1-phosphate

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

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,
• and purine ribonucleoside phosphorylase.

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

Function

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.

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.

• Thymidine can be phosphorylated by thymidine kinase (TK).
• Uridine can be phosphorylated by uridine kinase (UK).
• Cytidine can be phosphorylated by cytidine kinase (CK).
• Deoxycytidine can be phosphorylated by deoxycytidine kinase (DCK).

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

This protein may use the morpheein model of allosteric regulation.

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).

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

See also

• Purine nucleoside phosphorylase deficiency

Further reading

• Boyer, P.D., Lardy, H. and Myrback, K. (Eds.), The Enzymes, 2nd ed., vol. 5, Academic Press, New York, 1961, p. 237-255.

External links

• Human PNP at Cornell University
• E. Coli PNP at Cornell University
• Purine-Nucleoside Phosphorylase at the US National Library of Medicine Medical Subject Headings (MeSH)