PNPase

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Purine nucleoside phosphorylase, abbreviated as PNPase, is an enzyme involved in purine metabolism. Purine nucleoside phosphorylase can metabolize adenosine to adenine, inosine to hypoxanthine, and guanosine to guanine, and produce ribose-5-phosphate in these reactions. It should be noted that the acronym PNPase is also used for another unrelated enzyme, Polynucleotide Phosphorylase. Patients with purine nucleoside phosphorylase deficiency have immunodeficiency, and only T cells and B cells in the immune system are not affected by this deficiency. Human purine nucleoside phosphorylase (PNP) is a ubiquitous enzyme that plays a key role in the purine rescue pathway. The lack of human PNP can lead to impaired T cell function and usually has no significant effect on B cell function. PNP is highly specific for 6-oxopurine nucleoside, and its activity on 6-aminopurine nucleoside is negligible. The catalytic efficiency of inosine is 350,000 times higher than that of adenosine. Adenine nucleosides and nucleotides are deaminated by adenosine deaminase and AMP deaminase into their corresponding inosine derivatives, which can be further degraded.

Figure 1. Structure of PNPase.

Classification

According to PNP substrate specificity and molecular weight, PNP from different biological sources can be divided into high molecular weight homohexamer and low molecular weight homotrimer. Most bacterial PNPs are hexamers, the molecular weight of the subunit is 25kDa, the substrate specificity is not strong, and can accept adenosine, guanosine, inosine as substrates; mammals and some microorganisms (Bacillus cereus, Bacillus stearothmophilus TH 6-2 ) PNP is a trimer, the molecular weight of the subunit is 30~32kDa, and usually only accepts inosine and guanosine as substrates; some microorganisms, such as Escherichia coli, Bacillus subtilis, Bacillus stearothermophilus, both exist Aggregate PNP.

Functions

Purine nucleoside phosphorylase is an enzyme involved in purine metabolism. PNP metabolizes inosine to hypoxanthine and guanosine to guanine, producing ribose phosphate in each case. Nucleoside phosphorylase is an enzyme that cleaves nucleosides by phosphorylating ribose to produce nucleobases and ribose 1 phosphate. It is an enzyme in the nucleotide rescue pathway. When de novo synthesis pathways are interrupted or absent (as in the brain), these pathways allow the cell to produce monophosphate nucleotides. Usually, the de novo route is interrupted due to chemotherapeutic drugs such as methotrexate or methotrexate. All rescue pathway enzymes require high-energy phosphate donors, such as ATP or PRPP. Adenosine uses the enzyme adenosine kinase, which is a very important enzyme in cells. People are trying to develop an enzyme inhibitor for cancer chemotherapy.

Clinical significance

PNPase and adenosine deaminase (ADA) together play a key role in purine catabolism, which is called a rescue pathway. Mutations in ADA can cause (d) ATP accumulation, thereby inhibiting ribonucleotide reductase, leading to (d) CTP and (d) TTP deficiency, which in turn leads to apoptosis of T lymphocytes and B lymphocytes, leading to PNP deficiency. The patient will have immunodeficiency problems. It only affects T cells. B cells are not affected by defects.

Application

In the in vitro reaction, if another purine base or its analogue is added, a new purine nucleoside or analogue can be synthesized. It has been widely used in the production of nucleoside antiviral drugs by microbial enzymatic method, such as adenosine arabinoside, Ribavirin, etc.