Disease relevance of PNPO

• Second, PNPO negative hepatoma cell lines stably transfected with the PNPO cDNA express enzymatically active PNPO protein [1].
• In addition, human brain PNPO cDNA was expressed in Escherichia coli, and the roles of both the N- and C-terminal regions were studied by creating sequential truncation mutants [2].
• The molecular structure of Rv2074, a probable pyridoxine 5'-phosphate oxidase from Mycobacterium tuberculosis, at 1.6 angstroms resolution [3].

High impact information on PNPO

• Seizures ceased with the administration of PLP, having been resistant to treatment with pyridoxine, suggesting a defect of pyridox(am)ine 5'-phosphate oxidase (PNPO) [4].
• Levels of both pipecolic acid and certain metabolites shown to be elevated in patients with PNPO mutations should be measured, and therapeutic trials of pyridoxal phosphate as well as pyridoxine should be considered early in the course of the management of infants and young children with intractable seizures [5].
• In particular, pyridoxine- 5'-phosphate oxidase (PNPO), the rate-limiting enzyme in pyridoxal 5'-phosphate (PLP) biosynthesis, is absent in liver and neurally-derived tumors [1].
• Vigabatrin inhibits pyridoxine-5'-phosphate oxidase, not pyridoxal kinase in the hippocampus of seizure prone gerbils [6].
• Chronological changes in pyridoxine-5'-phosphate oxidase immunoreactivity in the seizure-sensitive gerbil hippocampus [7].

Chemical compound and disease context of PNPO

• Escherichia coli pyridoxine 5'-phosphate oxidase (ePNPOx) catalyzes the terminal step in the biosynthesis of pyridoxal 5'-phosphate (PLP) by the FMN oxidation of pyridoxine 5'-phosphate (PNP) or pyridoxamine 5'-phosphate (PMP), forming FMNH(2) and H(2)O(2) [8].

Biological context of PNPO

• The mRNA master dot-blot for multiple human tissues provided a complete map of the tissue distribution not only for PNPO but also for pyridoxal kinase and pyridoxal phosphatase [2].
• The absence of TATA-like sequences, the presence of Sp1-binding sites and more importantly, the presence of CpG islands in the regulatory region of the PNPO gene are characteristic features of housekeeping genes [2].
• The human PNPO gene is composed of seven exons and six introns, and spans approximately 8 kb [2].

Anatomical context of PNPO

• The major sites of PNPO expression are liver, skeletal muscle and kidneys while a very weak signal was detected in lung [2].
• A simple fluorimetric assay for pyridoxamine phosphate oxidase in erythrocyte haemolysates: effects of riboflavin supplementation and of glucose 6-phosphate dehydrogenase deficiency [9].

Associations of PNPO with chemical compounds

• Other studies demonstrate that some children with intractable seizures respond to pyridoxal phosphate rather than pyridoxine, including a rare form of neonatal epileptic encephalopathy shown to be due to mutations in the PNPO gene for pyridox(am)ine 5'-phosphate oxidase [5].
• Based on double immunofluorescence study, PLK and PNPO immunoreactive cells in the strata oriens and radiatum were identified as GABAergic cells [10].
• Therefore, decreases of PLK and PNPO in the hippocampal CA1 region of aged brains may be involved in aging processes related with gamma-aminobutyric acid (GABA) function [10].

Other interactions of PNPO

• Significant age-dependent changes in PLK and PNPO immunoreactivities were found in the CA1 region, but not in the CA2/3 region [10].

References