Purine nucleoside phosphorylase

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

Function
Purine nucleoside phosphorylase is an enzyme involved in purine metabolism. PNP metabolizes is_associated_with::adenosine into is_associated_with::adenine, is_associated_with::inosine into is_associated_with::hypoxanthine, and is_associated_with::guanosine into is_associated_with::guanine, in each case creating is_associated_with::ribose phosphate.

Nucleoside phosphorylase is an enzyme which cleaves a nucleoside by phosphorylating the ribose to produce a is_associated_with::nucleobase and ribose 1 phosphate. It is one enzyme of the is_associated_with::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 is_associated_with::chemotherapy drugs such as is_associated_with::methotrexate or is_associated_with::aminopterin.

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


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

is_associated_with::Adenosine uses the enzyme is_associated_with::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 is_associated_with::cancer chemotherapy.

Enzyme regulation
This protein may use the is_associated_with::morpheein model of is_associated_with::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 is_associated_with::ribonucleotide reductase, leading to a deficiency in (d)CTPs and (d)TTPs, which, in turn, induces is_associated_with::apoptosis in T-lymphocytes and B-lymphocytes, leading to is_associated_with::severe combined immunodeficiency (SCID).

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