Biology:Purine nucleoside phosphorylase
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| purine-nucleoside phosphorylase | |||||||||
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| EC number | 2.4.2.1 | ||||||||
| CAS number | 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 | ||||||||
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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.[2] It catalyzes the chemical reaction
- Purine Nucleoside + Inorganic Phosphate (Pi) Purine Base + α-D-Ribose 1-Phosphate
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.[3]
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.[4]
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).[5]
PNP-deficient patients will have an immunodeficiency problem. It affects only T-cells; B-cells are unaffected by the deficiency.
See also
References
- ↑ "Structures of human purine nucleoside phosphorylase complexed with inosine and ddI". Biochemical and Biophysical Research Communications 313 (4): 907–914. January 2004. doi:10.1016/j.bbrc.2003.11.179. PMID 14706628. Bibcode: 2004BBRC..313..907C.
- ↑ "Entrez Gene: NP nucleoside phosphorylase". https://www.ncbi.nlm.nih.gov/gene/4860.
- ↑ Kaplan USMLE Biochemistry Review
- ↑ "Dynamic dissociating homo-oligomers and the control of protein function". Archives of Biochemistry and Biophysics 519 (2): 131–143. March 2012. doi:10.1016/j.abb.2011.11.020. PMID 22182754.
- ↑ "Mutations in the human adenosine deaminase gene that affect protein structure and RNA splicing". Proceedings of the National Academy of Sciences of the United States of America 84 (16): 5947–5951. August 1987. doi:10.1073/pnas.84.16.5947. PMID 3475710.
Further reading
- "Purine nucleoside phosphorylase deficiency". Immunodeficiency Reviews 3 (1): 45–81. 1991. PMID 1931007.
- "Purine nucleoside phosphorylase in chronic lymphocytic leukemia (CLL)". Blood 52 (5): 886–895. November 1978. doi:10.1182/blood.V52.5.886.886. PMID 100152.
- "Molecular analysis of mutations in a patient with purine nucleoside phosphorylase deficiency". American Journal of Human Genetics 51 (4): 763–772. October 1992. PMID 1384322.
- "Exon skipping in purine nucleoside phosphorylase mRNA processing leading to severe immunodeficiency". The Journal of Biological Chemistry 267 (11): 7834–7838. April 1992. doi:10.1016/S0021-9258(18)42589-6. PMID 1560016.
- "Sequence and functional characterization of the human purine nucleoside phosphorylase promoter". Nucleic Acids Research 19 (18): 5015–5020. September 1991. doi:10.1093/nar/19.18.5015. PMID 1923769.
- "Three-dimensional structure of human erythrocytic purine nucleoside phosphorylase at 3.2 A resolution". The Journal of Biological Chemistry 265 (3): 1812–1820. January 1990. doi:10.2210/pdb2pnp/pdb. PMID 2104852.
- "A human purine nucleoside phosphorylase deficiency caused by a single base change". The Journal of Biological Chemistry 262 (5): 2332–2338. February 1987. doi:10.1016/S0021-9258(18)61658-8. PMID 3029074.
- "Human purine nucleoside phosphorylase cDNA sequence and genomic clone characterization". Nucleic Acids Research 12 (14): 5779–5787. July 1984. doi:10.1093/nar/12.14.5779. PMID 6087295.
- "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): 706–709. December 1996. doi:10.1007/s004390050290. PMID 8931706.
- "Mutations in purine nucleoside phosphorylase deficiency". Human Mutation 9 (2): 118–121. 1997. doi:10.1002/(SICI)1098-1004(1997)9:2<118::AID-HUMU3>3.0.CO;2-5. PMID 9067751.
- "Purine nucleoside phosphorylase. 1. Structure-function studies". Biochemistry 36 (39): 11725–11734. September 1997. doi:10.1021/bi961969w. PMID 9305962.
- "Purine nucleoside phosphorylase. 2. Catalytic mechanism". Biochemistry 36 (39): 11735–11748. September 1997. doi:10.1021/bi961970v. PMID 9305963.
- "Purine nucleoside phosphorylase. 3. Reversal of purine base specificity by site-directed mutagenesis". Biochemistry 36 (39): 11749–11756. September 1997. doi:10.1021/bi961971n. PMID 9305964.
- "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): 81–85. July 1998. doi:10.1007/s004390050787. PMID 9737781.
- "A DNA enzyme with N-glycosylase activity". Proceedings of the National Academy of Sciences of the United States of America 97 (14): 7802–7807. July 2000. doi:10.1073/pnas.97.14.7802. PMID 10884411. Bibcode: 2000PNAS...97.7802S.
- "Two novel mutations in a purine nucleoside phosphorylase (PNP)-deficient patient". Clinical Genetics 59 (6): 430–437. June 2001. doi:10.1034/j.1399-0004.2001.590608.x. PMID 11453975.
- "Identification of Ca2+-dependent binding partners for the neuronal calcium sensor protein neurocalcin delta: interaction with actin, clathrin and tubulin". The Biochemical Journal 363 (Pt 3): 599–608. May 2002. doi:10.1042/0264-6021:3630599. PMID 11964161.
- "Mitochondrial transcription factors B1 and B2 activate transcription of human mtDNA". Nature Genetics 31 (3): 289–294. July 2002. doi:10.1038/ng909. PMID 12068295.
- "Xanthosine and xanthine. Substrate properties with purine nucleoside phosphorylases, and relevance to other enzyme systems". European Journal of Biochemistry 269 (16): 4048–4057. August 2002. doi:10.1046/j.1432-1033.2002.03097.x. PMID 12180982.
- "Purine nucleoside phosphorylase from human erythrocytes. IV. Crystallization and some properties". The Journal of Biological Chemistry 244 (4): 644–647. February 1969. doi:10.1016/S0021-9258(18)94403-0. PMID 5768862.
- The Enzymes. 5 (2nd ed.). New York: Academic Press. 1961. pp. 237-255.
- "Phosphorolysis and hydrolysis of purine ribosides by enzymes from yeast". The Journal of Biological Chemistry 198 (2): 683–694. October 1952. doi:10.1016/S0021-9258(18)55525-3. PMID 12999785.
- "The enzymatic synthesis of purine ribosides". The Journal of Biological Chemistry 167 (2): 477–486. February 1947. doi:10.1016/S0021-9258(17)31000-1. PMID 20285042.
- "Purification and comparative properties of a pyrimidine nucleoside phosphorylase from Bacillus stearothermophilus". The Journal of Biological Chemistry 244 (13): 3691–3697. July 1969. doi:10.1016/S0021-9258(18)83424-X. PMID 4978445.
- "Enzymes of the human erythrocyte. I. Purine nucleoside phosphorylase; isolation procedure". The Journal of Biological Chemistry 224 (2): 879–887. February 1957. doi:10.1016/S0021-9258(18)64980-4. PMID 13405917.
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)
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