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Information on EC 1.4.3.5 - pyridoxal 5'-phosphate synthase and Organism(s) Homo sapiens
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1.4.3.5 pyridoxal 5'-phosphate synthaseIUBMB Comments
A flavoprotein (FMN). In Escherichia coli, the coenzyme pyridoxal 5'-phosphate is synthesized de novo by a pathway that involves EC 1.2.1.72 (erythrose-4-phosphate dehydrogenase), EC 1.1.1.290 (4-phosphoerythronate dehydrogenase), EC 2.6.1.52 (phosphoserine transaminase), EC 1.1.1.262 (4-hydroxythreonine-4-phosphate dehydrogenase), EC 2.6.99.2 (pyridoxine 5'-phosphate synthase) and EC 1.4.3.5 (with pyridoxine 5'-phosphate as substrate). N4'-Substituted pyridoxamine derivatives are also oxidized in reaction (1) to form pyridoxal 5-phosphate and the corresponding primary amine.
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The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Reaction Schemes
Synonyms
pyridoxine 5'-phosphate oxidase, pnpox, pyridoxine phosphate oxidase, pyridox(am)ine 5'-phosphate oxidase, pnp oxidase, pyridoxine-5'-phosphate oxidase, pyridoxamine 5'-phosphate oxidase, pyridoxamine phosphate oxidase, pyridoxine (pyridoxamine) phosphate oxidase, pyridoxine (pyridoxamine) 5'-phosphate oxidase, 
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topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
FprA protein
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-
-
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oxidase, pyridoxamine phosphate
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PMP oxidase
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PNP/PMP oxidase
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PNPO
PNPOx
pyridoxamine 5'-phosphate oxidase
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pyridoxamine phosphate oxidase
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pyridoxamine-phosphate oxidase
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pyridoxaminephosphate oxidase (EC 1.4.3.5: deaminating)
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pyridoxine (pyridoxamine) 5'-phosphate oxidase
pyridoxine (pyridoxamine) phosphate oxidase
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pyridoxine 5'-phosphate oxidase
PNPOx
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pyridoxine (pyridoxamine) 5'-phosphate oxidase
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Deamination
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oxidation
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redox reaction
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reduction
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PATHWAY SOURCE
PATHWAYS
BRENDA
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-, -, -, -
SYSTEMATIC NAME
IUBMB Comments
pyridoxamine-5'-phosphate:oxygen oxidoreductase (deaminating)
A flavoprotein (FMN). In Escherichia coli, the coenzyme pyridoxal 5'-phosphate is synthesized de novo by a pathway that involves EC 1.2.1.72 (erythrose-4-phosphate dehydrogenase), EC 1.1.1.290 (4-phosphoerythronate dehydrogenase), EC 2.6.1.52 (phosphoserine transaminase), EC 1.1.1.262 (4-hydroxythreonine-4-phosphate dehydrogenase), EC 2.6.99.2 (pyridoxine 5'-phosphate synthase) and EC 1.4.3.5 (with pyridoxine 5'-phosphate as substrate). N4'-Substituted pyridoxamine derivatives are also oxidized in reaction (1) to form pyridoxal 5-phosphate and the corresponding primary amine.
CAS REGISTRY NUMBER
COMMENTARY
9029-21-4
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
pyridoxamine 5'-phosphate + H2O + O2
pyridoxal 5'-phosphate + NH3 + H2O2
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-
-
?
pyridoxamine 5'-phosphate + H2O + O2
pyridoxal 5'-phosphate + NH3 + H2O2
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-
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?
pyridoxamine 5'-phosphate + H2O + O2
pyridoxal 5'-phosphate + NH3 + H2O2
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-
-
-
?
pyridoxamine 5'-phosphate + H2O + O2
pyridoxal 5'-phosphate + NH3 + H2O2
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-
-
?
pyridoxamine 5'-phosphate + H2O + O2
pyridoxal 5'-phosphate + NH3 + H2O2
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6 to 7fold more active as with pyridoxamine 5'-phosphate
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?
pyridoxamine 5'-phosphate + H2O + O2
pyridoxal 5'-phosphate + NH3 + H2O2
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enzyme plays a role in regulation of vitamin B-6 metabolism in erythrocytes
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?
pyridoxamine 5'-phosphate + H2O + O2
pyridoxal 5'-phosphate + NH3 + H2O2
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terminal step in de novo biosynthesis of pyridoxal 5'-phosphate
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-
?
pyridoxine 5'-phosphate + H2O + O2
pyridoxal 5'-phosphate + H2O2
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?
pyridoxine 5'-phosphate + H2O + O2
pyridoxal 5'-phosphate + H2O2
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terminal step in de novo biosynthesis of pyridoxal 5'-phosphate
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-
?
pyridoxine 5'-phosphate + O2
pyridoxal 5'-phosphate + H2O2
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-
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?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
pyridoxamine 5'-phosphate + H2O + O2
pyridoxal 5'-phosphate + NH3 + H2O2
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-
-
-
?
pyridoxamine 5'-phosphate + H2O + O2
pyridoxal 5'-phosphate + NH3 + H2O2
-
-
-
?
pyridoxamine 5'-phosphate + H2O + O2
pyridoxal 5'-phosphate + NH3 + H2O2
-
enzyme plays a role in regulation of vitamin B-6 metabolism in erythrocytes
-
?
pyridoxamine 5'-phosphate + H2O + O2
pyridoxal 5'-phosphate + NH3 + H2O2
-
terminal step in de novo biosynthesis of pyridoxal 5'-phosphate
-
-
?
pyridoxine 5'-phosphate + H2O + O2
pyridoxal 5'-phosphate + H2O2
-
terminal step in de novo biosynthesis of pyridoxal 5'-phosphate
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-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pyridoxal 5'-phosphate
the enzyme has an allosteric pyridoxal 5'-phosphate binding site that plays a crucial role in the enzyme regulation and therefore in the regulation of vitamin B6 metabolism in humans
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0026
pyridoxine 5'-phosphate
pH 7.6, 37°C, wild-type enzyme, TRIS buffer
0.0028
pyridoxine 5'-phosphate
pH 7.6, 37°C, wild-type enzyme, HEPES buffer
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.057
pyridoxine 5'-phosphate
pH 7.6, 37°C, wild-type enzyme, HEPES buffer
0.062
pyridoxine 5'-phosphate
pH 7.6, 37°C, wild-type enzyme, TRIS buffer
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.005
pyridoxal 5'-phosphate
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pH and temperature not specified in the publication
3.8
pyridoxal 5'-phosphate
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pH 8.5, 25°C, pyridoxine 5'-phosphate as substrate, wild-type enzyme
23
pyridoxal 5'-phosphate
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pH 8.5, 25°C, pyridoxine 5'-phosphate as substrate, mutant enzyme DELTA1-56
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
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3.3 nmol/g hemoglobin/h, subject with a slow rate of pyridoxine conversion
additional information
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7.8 nmol/g hemoglobin/h, subject with a slow rate of pyridoxine conversion given 24 mg/day oral riboflavin for 2 weeks
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
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14% of the activity in liver detected in left atrium, 11.6% of the activity in liver detected in tight atrium
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13.3% of the activity in liver detected in left cerebellum, 25.0% of the activity in liver detected in the right cerebellum
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1.2% of the activity in liver detected in ascending colon, 7.9% of the activity in liver is detected in transverse colon, 2.8% of the activity in liver is detected in descending colon
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20.5% of the activity in liver detected in the right ventricle
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
the enzyme (PNPO) is upregulated in patients with invasive ductal carcinoma (IDC) and is correlated with the overall survival of patients with metastasis at the later stages
malfunction
enzyme (PNPO) deficiency is responsible o severe neonatal encephalopathy, responsive to pyridoxal-5'-phosphate (PLP) or pyridoxine
malfunction
the pathogenic forms of pyridoxine 5'-phosphate oxidase is associated with neonatal epileptic encephalopathy
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PNPO_HUMAN
261
0
29988
Swiss-Prot
Mitochondrion (Reliability: 5)
J3QQV6_HUMAN
165
0
19085
TrEMBL
Mitochondrion (Reliability: 5)
A0A286YFL3_HUMAN
151
0
17473
TrEMBL
other Location (Reliability: 2)
J3QQZ9_HUMAN
238
0
27312
TrEMBL
other Location (Reliability: 4)
Q53FP0_HUMAN
261
0
29916
TrEMBL
Mitochondrion (Reliability: 5)
V9HW45_HUMAN
261
0
29988
TrEMBL
Mitochondrion (Reliability: 5)
PDB
SCOP
CATH
UNIPROT
ORGANISM
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
homodimer
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging-drop and sitting-drop method, crystallized without and with an excess of pyridoxal 5'-phosphate. Structures are determined to 1.95 A and 2.65 A, respectively
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PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
DELTA1-56
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3.35fold increase in KM-value for pyridoxamine 5'-phosphate compared to wild-type enzyme, 2.95fold increase in KM-value for pyridoxine 5'-phosphate compared to wild-type enzyme, 6fold increase in KI-value for pyridoxal 5'-phosphate compared to wild-type enzyme
G118R
pathogenic variant that is responsible for pyridoxamine 5'-phosphate oxidase deficiency. 51% of the activity as compared to wild-type enzyme. Tm-value of the mutant enzyme (in absence and presence of FMN) is about 10°C lower than the Tm-value of the wilde-type enzyme
R116Q
R116Q/R225H
pathogenic variant that is responsible for pyridoxamine 5'-phosphate oxidase deficiency. The Tm-value of the mutant enzyme in absence of FMN is 5.3°C lower than the Tm-value of the wilde-type enzyme in absence of FMN. The Tm-value of the mutant enzyme in absence of FMN is 4.7°C lower than the Tm-value of the wilde-type enzyme in presence of FMN
R118Q
later onset of symptoms of severe encephalopathy (beyond the first months of life) and peculiar epileptic manifestations in patients
R141C
pathogenic variant that is responsible for pyridoxamine 5'-phosphate oxidase deficiency. The Tm-value of the mutant enzyme in absence of FMN is 6.2°C lower than the Tm-value of the wilde-type enzyme in absence of FMN. The Tm-value of the mutant enzyme in absence of FMN is 6.0°C lower than the Tm-value of the wilde-type enzyme in presence of FMN
R225H
pathogenic variant that is responsible for pyridoxamine 5'-phosphate oxidase deficiency. The Tm-value of the mutant enzyme in absence of FMN is 5.1°C higher than the Tm-value of the wilde-type enzyme in absence of FMN. The Tm-value of the mutant enzyme in absence of FMN is 3.8°C lower than the Tm-value of the wilde-type enzyme in presence of FMN
R229W
R95C
R95H
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the mutation is associated with lethality in neonatal epileptic encephalopathy
X262Q
pathogenic variant that is responsible for pyridoxamine 5'-phosphate oxidase deficiency. The Tm-value of the mutant enzyme in absence of FMN is 2.7°C lower than the Tm-value of the wilde-type enzyme in absence of FMN. The Tm-value of the mutant enzyme in absence of FMN is 4.7°C lower than the Tm-value of the wilde-type enzyme in presence of FMN
R116Q
the Tm-value of the mutant enzyme in absence of FMN is 7.2°C lower than the Tm-value of the wilde-type enzyme in absence of FMN. The Tm-value of the mutant enzyme in absence of FMN is 8.2°C lower than the Tm-value of the wilde-type enzyme in presence of FMN
R229W
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the mutation is associated with lethality in neonatal epileptic encephalopathy
R229W
the mutation leads to deficiency of pyridoxal 5'-phosphate in the cell and causes neonatal epileptic encephalopathy
R95C
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the mutation is associated with lethality in neonatal epileptic encephalopathy
R95C
the mutation leads to deficiency of pyridoxal 5'-phosphate in the cell and causes neonatal epileptic encephalopathy. The mutant exhibits a 15fold reduction in affinity for the FMN cofactor, a 71fold decrease in affinity for the substrate pyridoxine 5'-phosphate, a 4.9fold decrease in specific activity, and a 343fold reduction in catalytic activity, compared to the wild type enzyme
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
50.1
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
several pyridoxamine 5'-phosphate oxidase pathogenic variants responsible for pyridoxamine 5'-phosphate oxidase deficiency (G118R, R141C, R225H, R116Q/R225H, and X262Q) are recombinantly expressed in Escherichia coli
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the enzyme (PNPO) is down-regulated and up-regulated by miR-216b-5p mimics and inhibitors, respectively, in breast cancer cells
the enzyme (PNPO) is down-regulated and up-regulated by miR-216b-5p mimics and inhibitors, respectively, in breast cancer cells. Knockdown of MALAT1 results in an increase of miR-216b-5p and a decrease of PNPO mRNA, indicating a regulatory mechanism of competing endogenous RNAs
the enzyme is upregulated in patients with invasive ductal carcinoma (IDC) at mRNA and protein levels
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Merrill, A.H.; Wang, E.
Highly sensitive methods for assaying the enzymes of vitamin B6 metabolism
Methods Enzymol.
122
110-115
1986
Oryctolagus cuniculus, Homo sapiens
Clements, J.E.; Anderson, B.B.
Glutathione reductase activity and pyridoxine (pyridoxamine) phosphate oxidase activity in the red cell
Biochim. Biophys. Acta
632
159-163
1980
Homo sapiens
Clements, J.E.; Anderson, B.B.
Pyridoxine (pyridoxamine) phosphate oxidase activity in the red cell
Biochim. Biophys. Acta
613
401-409
1980
Homo sapiens
Kang, J.H.; Hong, M.L.; Kim, D.W.; Park, J.; Kang, T.C.; Won, M.H.; Baek, N.I.; Moon, B.J.; Choi, S.Y.; Kwon, O.S.
Genomic organization, tissue distribution and deletion mutation of human pyridoxine 5'-phosphate oxidase
Eur. J. Biochem.
271
2452-2461
2004
Homo sapiens
Musayev, F.N.; Di Salvo, M.L.; Ko, T.P.; Schirch, V.; Safo, M.K.
Structure and properties of recombinant human pyridoxine 5'-phosphate oxidase
Protein Sci.
12
1455-1463
2003
Homo sapiens
di Salvo, M.L.; Contestabile, R.; Safo, M.K.
Vitamin B6 salvage enzymes: mechanism, structure and regulation
Biochim. Biophys. Acta
1814
1597-1608
2011
Escherichia coli, Homo sapiens
Ghatge, M.S.; Karve, S.S.; David, T.M.; Ahmed, M.H.; Musayev, F.N.; Cunningham, K.; Schirch, V.; Safo, M.K.
Inactive mutants of human pyridoxine 5-phosphate oxidase a possible role for a noncatalytic pyridoxal 5-phosphate tight binding site
FEBS Open Bio
6
398-408
2016
Homo sapiens (Q9NVS9), Homo sapiens
Ren, W.; Guan, W.; Zhang, J.; Wang, F.; Xu, G.
Pyridoxine 5-phosphate oxidase is correlated with human breast invasive ductal carcinoma development
Aging
11
2151-2176
2019
Homo sapiens (Q9NVS9), Homo sapiens
di Salvo, M.L.; Mastrangelo, M.; Nogues, I.; Tolve, M.; Paiardini, A.; Carducci, C.; Mei, D.; Montomoli, M.; Tramonti, A.; Guerrini, R.; Contestabile, R.; Leuzzi, V.
Biochemical data from the characterization of a new pathogenic mutation of human pyridoxine-5-phosphate oxidase (PNPO)
Data Brief
15
868-875
2017
Homo sapiens (Q9NVS9), Homo sapiens
EXTERNAL LINKS (specific for EC-Number 1.4.3.5)
Transporter Classification Database (TCDB): 2.A.7.2.4
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