Pyridoxine 5′-phosphate oxidase

Pyridoxal 5′-phosphate synthase
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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Pyridoxine 5′-phosphate oxidase is an

Concurrently, the other oxygen atom is reduced to water. Even though molecular oxygen is the electron acceptor in these enzymes' reactions, they are unique because oxygen does not appear in the oxidized product.

The active form of

Structure

Pyridoxine 5′-phosphate oxidase is a

Cofactors are ions or coenzymes necessary for enzyme activity. The FMN is located in a deep cleft (formed by the two polypeptide subunits), and held in place by extensive hydrogen-bond interactions with the protein. In this particular case, the FMN helps the enzyme to bind the substrates. In the absence of pyridoxal 5′-phosphate (PLP), the active site of the enzyme is in an “open” conformation. Once substrate binds and is converted to PLP, the active site of the enzyme is in a partially “closed” conformation. Specific amino acid residues can form hydrogen bonds with the PLP, thus forming a lid that physically covers the active site, giving rise to the “closed” conformation.^[7]

Pathway

Pyridoxine 5′-phosphate oxidase is the enzyme that catalyzes the rate-limited step of the B₆ metabolism pathway. Vitamin B₆, which is also known as

Reactions

Pyridoxine 5′-phosphate oxidase catalyzes several reactions; the two most important are the deamination of pyridoxamine 5′-phosphate and the deamination of pyridoxine 5-phosphate, both of which are key intermediates in the metabolism of B₆.^[8] Pyridoxine 5′-phosphate oxidase's EC number is 1.4.3.5.^[6]

pyridoxamine 5′-phosphate +

O₂ → pyridoxal 5′-phosphate + NH₃ + H₂O₂

pyridoxine phosphate + O₂ ⇌ H₂O₂ + pyridoxal phosphate

Pyridoxine 5′-phosphate oxidase also plays a role in nitrogen metabolism, converting amines to aldehydes and NH₃ by the reaction:

amine + H₂O + O₂ ⇌ aldehyde + NH₃ + H₂O₂

Kinetics

In humans, the pyridoxine 5′-phosphate oxidase enzyme exhibits a low catalytic

Pyridoxine 5′-phosphate oxidase in different organisms

Pyridoxine 5′-phosphate oxidase has been highly conserved over time, as there are many similarities between the enzyme as it is found in humans and Escherichia coli. Although there is only 39% retention of amino acid sequence from the E. coli version of the enzyme to the human version, the sequences for the FMN binding site and the substrate active sites are among the very highly conserved portion. One of the key differences is that the human pyridoxine 5′-phosphate oxidase has a higher specificity for the pyridoxamine 5′-phosphate substrate, whereas the pyridoxine 5′-phosphate oxidase in E. coli has a higher specificity pyridoxal 5′-phosphate substrate.^[9]

Clinical significance

Mutations of the PNPO gene may result in the development of pyridoxamine 5'-phosphate oxidase deficiency, a disease presenting soon after birth with seizures and subsequent encephalopathy.

References

Further reading

• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4.
  PMID 8125298
  .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56.
  PMID 9373149
  .
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903.
  PMID 12477932
  .
• Musayev FN, Di Salvo ML, Ko TP, et al. (2004). "Structure and properties of recombinant human pyridoxine 5′-phosphate oxidase". Protein Sci. 12 (7): 1455–63.
  PMID 12824491
  .
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5.
  PMID 14702039
  .
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7.
  PMID 15489334
  .
• Mills PB, Surtees RA, Champion MP, et al. (2005). "Neonatal epileptic encephalopathy caused by mutations in the PNPO gene encoding pyridox(am)ine 5'-phosphate oxidase". Hum. Mol. Genet. 14 (8): 1077–86.
  PMID 15772097
  .
• Kimura K, Wakamatsu A, Suzuki Y, et al. (2006). "Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes". Genome Res. 16 (1): 55–65.
  PMID 16344560
  .

External links

• Media related to Pyridoxine 5'-phosphate oxidase at Wikimedia Commons