Purine nucleoside phosphorylase
Class of enzymes
From Wikipedia, the free encyclopedia
Purine nucleoside phosphorylase, PNP, PNPase or inosine phosphorylase (EC 2.4.2.1) is an enzyme that in humans is encoded by the PNP gene.[6] It catalyzes the chemical reaction
- Purine Nucleoside + Inorganic Phosphate (Pi) Purine Base + α-D-Ribose 1-Phosphate
| purine-nucleoside phosphorylase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| |||||||||
| Identifiers | |||||||||
| EC no. | 2.4.2.1 | ||||||||
| CAS no. | 9030-21-1 | ||||||||
| 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 / QuickGO | ||||||||
| |||||||||
The enzyme catalyzes reversible interconversion of purine nucleoside and phosphate into purine base and α-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
- purine ribonucleoside phosphorylas
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-1-phosphate. In humans, adenosine is first metabolized to inosine via the enzyme adenosine deaminase.[7]
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. For pyrimidine nucleosides:
- Thymidine can be phosphorylated by thymidine kinase.
- Uridine can be phosphorylated by uridine kinase.
- Cytidine can be phosphorylated by cytidine kinase.
- Deoxycytidine can be phosphorylated by deoxycytidine kinase.
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
PNP protein may use the morpheein model of allosteric regulation.[8]
Clinical significance
Purine nucleoside phosphorylase, together with adenosine deaminase (ADA), serves a key role in purine catabolism. Mutations in ADA lead to an accumulation of dATP, which inhibits ribonucleotide reductase, leading to a deficiency in dCTP and dTTP, which, in turn, induces apoptosis in T-lymphocytes and B-lymphocytes, leading to severe combined immunodeficiency (SCID).[9]
PNP-deficient patients will have an immunodeficiency problem. It affects only T-cells; B-cells are unaffected by the deficiency.
