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Purine nucleoside phosphorylase, PNP, PNPase or inosine phosphorylase (EC2.4.2.1) is an enzyme that in humans is encoded by the NPgene.[2] It catalyzes the chemical reaction
This enzyme belongs to the family of glycosyltransferases, specifically the pentosyltransferases. The systematic name of this enzyme class is purine-nucleoside:phosphate ribosyltransferase.
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]
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.
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.
Ealick SE, Rule SA, Carter DC, Greenhough TJ, Babu YS, Cook WJ, Habash J, Helliwell JR, Stoeckler JD, Parks RE (Jan 1990). "Three-dimensional structure of human erythrocytic purine nucleoside phosphorylase at 3.2 A resolution". The Journal of Biological Chemistry. 265 (3): 1812–20. doi:10.2210/pdb2pnp/pdb. PMID2104852.
Pannicke U, Tuchschmid P, Friedrich W, Bartram CR, Schwarz K (Dec 1996). "Two novel missense and frameshift mutations in exons 5 and 6 of the purine nucleoside phosphorylase (PNP) gene in a severe combined immunodeficiency (SCID) patient". Human Genetics. 98 (6): 706–9. doi:10.1007/s004390050290. PMID8931706. S2CID5657916.
Stoeckler JD, Poirot AF, Smith RM, Parks RE, Ealick SE, Takabayashi K, Erion MD (Sep 1997). "Purine nucleoside phosphorylase. 3. Reversal of purine base specificity by site-directed mutagenesis". Biochemistry. 36 (39): 11749–56. doi:10.1021/bi961971n. PMID9305964.
Sasaki Y, Iseki M, Yamaguchi S, Kurosawa Y, Yamamoto T, Moriwaki Y, Kenri T, Sasaki T, Yamashita R (Jul 1998). "Direct evidence of autosomal recessive inheritance of Arg24 to termination codon in purine nucleoside phosphorylase gene in a family with a severe combined immunodeficiency patient". Human Genetics. 103 (1): 81–5. doi:10.1007/s004390050787. PMID9737781. S2CID8373698.
Dalal I, Grunebaum E, Cohen A, Roifman CM (Jun 2001). "Two novel mutations in a purine nucleoside phosphorylase (PNP)-deficient patient". Clinical Genetics. 59 (6): 430–7. doi:10.1034/j.1399-0004.2001.590608.x. PMID11453975. S2CID24624559.
Falkenberg M, Gaspari M, Rantanen A, Trifunovic A, Larsson NG, Gustafsson CM (Jul 2002). "Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA". Nature Genetics. 31 (3): 289–94. doi:10.1038/ng909. PMID12068295. S2CID11164308.