Information on EC 1.5.3.13 - N1-acetylpolyamine oxidase

Word Map on EC 1.5.3.13
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Specify your search results
Select one or more organisms in this record:
Show additional data
Do not include text mining results
Include (text mining) results (more...)
Include results (AMENDA + additional results, but less precise; more...)

The enzyme appears in viruses and cellular organisms

EC NUMBER
COMMENTARY hide
1.5.3.13
-
RECOMMENDED NAME
GeneOntology No.
N1-acetylpolyamine oxidase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
N1-acetylspermidine + O2 + H2O = putrescine + 3-acetamidopropanal + H2O2
show the reaction diagram
-
-
-
-
N1-acetylspermine + O2 + H2O = spermidine + 3-acetamidopropanal + H2O2
show the reaction diagram
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
spermine and spermidine degradation I
-
-
polyamine pathway
-
-
SYSTEMATIC NAME
IUBMB Comments
N1-acetylpolyamine:oxygen oxidoreductase (3-acetamidopropanal-forming)
The enzyme also catalyses the reaction: N1,N12-diacetylspermine + O2 + H2O = N1-acetylspermidine + 3-acetamamidopropanal + H2O2 [1]. No or very weak activity with spermine, or spermidine in absence of aldehydes. In presence of aldehydes the enzyme catalyses the reactions: 1. spermine + O2 + H2O = spermidine + 3-aminopropanal + H2O2, and with weak efficiency 2. spermidine + O2 + H2O = putrescine + 3-aminopropanal + H2O2 [2]. A flavoprotein (FAD). This enzyme, encoded by the PAOX gene, is found in mammalian peroxisomes and oxidizes N1-acetylated polyamines at the exo (three-carbon) side of the secondary amine, forming 3-acetamamidopropanal. Since the products of the reactions are deacetylated polyamines, this process is known as polyamine back-conversion. Differs in specificity from EC 1.5.3.14 [polyamine oxidase (propane-1,3-diamine-forming)], EC 1.5.3.15 [N8-acetylspermidine oxidase (propane-1,3-diamine-forming)], EC 1.5.3.16 (spermine oxidase) and EC 1.5.3.17 (non-specific polyamine oxidase).
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
-
the enzyme is involved in polyamine catabolic pathways, overview
physiological function
-
polyamine oxidation is a major pathway for reactive oxygen species production in prostate, inhibiting this pathway successfully delays prostate cancer progression
additional information
-
method development for determination of polyamines and acetylpolyamines in the polyamine catabolic pathway creating heptafluorobutyryl derivatives of the compounds for TOF and hybrid tandem mass spectrometry, overview
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(R)-alpha-methylspermidine + O2 + H2O
?
show the reaction diagram
-
PAO supplemented with benzaldehyde predominantly catalyzes the cleavage of (R)-isomer of alpha-methylspermidine, whereas in the presence of pyridoxal the (S)-alpha-methylspermidine is preferred
-
-
?
(S)-alpha-methylspermidine + O2 + H2O
?
show the reaction diagram
-
PAO supplemented with benzaldehyde predominantly catalyzes the cleavage of (R)-isomer of alpha-methylspermidine, whereas in the presence of pyridoxal the (S)-alpha-methylspermidine is preferred
-
-
?
(S)-N1-(2-methyl-1-butyl)-N11-ethyl-4,8-diazaundecane-1,11-diamine + O2 + H2O
?
show the reaction diagram
-
-
-
-
?
1-amino-8-acetamido-5-azanonane + O2 + H2O
?
show the reaction diagram
-
less preferred substrate
-
-
?
alpha-methylspermidine + O2 + H2O
?
show the reaction diagram
-
weak oxidation in presence of benzaldehyde, no oxidation without benzaldehyde
-
-
?
alpha-methylspermine + O2 + H2O
?
show the reaction diagram
-
oxidation in presence of benzaldehyde, no oxidation without benzaldehyde
-
-
?
alpha-methylspermine + O2 + H2O
spermidine + alpha-methylspermidine + ?
show the reaction diagram
-
-
-
-
?
bis-alpha,alpha'-methylspermine + O2 + H2O
alpha-methylspermidine + ?
show the reaction diagram
-
-
-
-
?
N,N'-bis-(3-benzylaminopropyl)butane-1,4-diamine + O2 + H2O
N1-(3-benzylaminopropyl)butane-1,4-diamine + H2O2 + ?
show the reaction diagram
-
-
main product
-
?
N,N'-bis-(3-ethylaminopropyl)butane-1,4-diamine + O2 + H2O
N1-(3-ethylaminopropyl)butane-1,4-diamine + H2O2 + ?
show the reaction diagram
-
minor N4-endo cleavage pathways resulting in formation of N1-ethylpropane-1,3-diamine
-
-
?
N-(3-benzylaminopropyl)-N'-(3-ethylaminopropyl)butane-1,4-diamine + O2 + H2O
N1-(3-ethylaminopropyl)butane-1,4-diamine + H2O2 + ?
show the reaction diagram
-
-
-
-
?
N1,N11-bis(ethyl)-norspermine + O2 + H2O
?
show the reaction diagram
-
-
-
-
?
N1,N11-diacetylnorspermine + O2 + H2O
?
show the reaction diagram
-
-
-
-
?
N1,N11-didansylnorspermine + O2 + H2O
1-dansylnorspermidine + 1-dansylamido-3-propanal + H2O2
show the reaction diagram
N1,N11-didansylnorspermine + O2 + H2O
? + H2O2
show the reaction diagram
-
-
-
-
?
N1,N11-didansylnorspermine + O2 + H2O
N1-acetylspermidine + 3-acetamidopropanal + H2O2
show the reaction diagram
-
-
-
-
?
N1,N11-diethylnorspermine + O2 + H2O
?
show the reaction diagram
-
-
-
?
N1,N12-bis(ethyl)-spermine + O2 + H2O
?
show the reaction diagram
-
-
-
-
?
N1,N12-bisethylspermine + H2O
?
show the reaction diagram
mechanistic studies
-
-
?
N1,N12-diacetylspermine + O2 + H2O
?
show the reaction diagram
N1,N12-diacetylspermine + O2 + H2O
N1-acetylspermidine + 3-acetamidopropanal + H2O2
show the reaction diagram
N1,N12-diethylspermine + O2 + H2O
?
show the reaction diagram
-
-
-
?
N1,N14-diethylhomospermine + O2 + H2O
?
show the reaction diagram
-
-
-
?
N1-(3-benzylaminopropyl)butane-1,4-diamine + O2 + H2O
spermidine + H2O2 + benzylalcohol
show the reaction diagram
-
-
-
-
?
N1-acetylspermidine + O2 + H2O
?
show the reaction diagram
N1-acetylspermidine + O2 + H2O
putrescine + 3-acetamidopropanal
show the reaction diagram
-
-
-
?
N1-acetylspermidine + O2 + H2O
putrescine + 3-acetamidopropanal + H2O2
show the reaction diagram
N1-acetylspermidine + O2 + H2O
putrescine + 3-acetaminopropanal + H2O2
show the reaction diagram
-
-
-
-
?
N1-acetylspermine + O2 + H2O
?
show the reaction diagram
N1-acetylspermine + O2 + H2O
spermidine + 3-acetamidopropanal + H2O
show the reaction diagram
PAO preferentially oxidizes acetylspermine or acetylspermidine over spermine
-
-
?
N1-acetylspermine + O2 + H2O
spermidine + 3-acetamidopropanal + H2O2
show the reaction diagram
N1-acetylspermine + O2 + H2O
spermidine + 3-acetaminopropanal + H2O2
show the reaction diagram
-
-
-
-
?
N1-benzyl-propane-1,3-diamine + O2 + H2O
propane-1,3-diamine + H2O2 + benzylalcohol
show the reaction diagram
-
-
-
-
?
N1-cyclopropylmethyl-N11-ethylnorspermine + O2 + H2O
?
show the reaction diagram
-
-
-
-
?
N1-ethyl-N11-(cycloheptyl)methyl-4,8-diazaundecane + O2 + H2O
?
show the reaction diagram
-
-
-
-
?
N1-ethyl-N11-(cyclopropyl)methyl-4,8-diazaundecane + O2 + H2O
?
show the reaction diagram
-
-
-
-
?
spermidine + O2 + H2O
?
show the reaction diagram
spermine + O2 + H2O
?
show the reaction diagram
spermine + O2 + H2O
spermidine + 3-aminopropanal + H2O2
show the reaction diagram
least favoured substrate
-
-
?
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
N1,N11-didansylnorspermine + O2 + H2O
N1-acetylspermidine + 3-acetamidopropanal + H2O2
show the reaction diagram
-
-
-
-
?
N1,N12-diacetylspermine + O2 + H2O
?
show the reaction diagram
-
-
-
-
?
N1,N12-diacetylspermine + O2 + H2O
N1-acetylspermidine + 3-acetamidopropanal + H2O2
show the reaction diagram
-
-
-
-
?
N1-acetylspermidine + O2 + H2O
?
show the reaction diagram
-
-
-
-
?
N1-acetylspermidine + O2 + H2O
putrescine + 3-acetamidopropanal + H2O2
show the reaction diagram
-
-
-
-
?
N1-acetylspermidine + O2 + H2O
putrescine + 3-acetaminopropanal + H2O2
show the reaction diagram
-
-
-
-
?
N1-acetylspermine + O2 + H2O
?
show the reaction diagram
-
-
-
-
?
N1-acetylspermine + O2 + H2O
spermidine + 3-acetamidopropanal + H2O2
show the reaction diagram
-
-
-
-
?
N1-acetylspermine + O2 + H2O
spermidine + 3-acetaminopropanal + H2O2
show the reaction diagram
-
-
-
-
?
additional information
?
-
Q6QHF9
PAO expression is inducible by polyamine analogues and thus may contribute to the inhibition of cell growth
-
-
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,12-diaminododecane
-
1,12-diaminododecane derivatives could represent good candidates for the development of novel highly specific mPAO inhibitors
1,8-diaminooctane
-
competitive versus the polyamine
guazatine
-
-
MDL72527
N,N'-butanedienyl butanediamine
-
i.e. MDL 72527 or CPC-200, a small molecule specific inhibitor of polyamine oxidase, effectively blocks androgen-induced reactive oxygen species production in human prostate cancer cells, as well as significantly delays prostate cancer progression and death in animals developing spontaneous prostate cancer
N-prenylagmatine
-
-
N1,N4-bis(2,3-butadienyl)-1,4-butanediamine
-
i.e. MDL 72,527
N1-acetyl-1,12-diaminododecane
-
competitive versus the polyamine
N1-acetyl-1,8-diaminooctane
-
competitive versus the polyamine
N1-acetyl-N3-pentyl-1,3-diaminopropane
-
competitive versus the polyamine
N8-acetylspermine
-
-
putrescine
-
-
SL-11144
-
0.01 mM, 80% inhibition
SL-11150
-
0.01 mM, complete inhibition
SL-11158
-
0.01 mM, complete inhibition
spermidine
-
-
spermine
-
-
additional information
-
no inhibition at pH 7.5: 1,8-diaminooctane. Comparative study on murine PAO (mPAO) and SMO (mSMO) inhibition. The different behaviour displayed by 1,12-diaminododecane towards mPAO and mSMO reveals the occurrence of basic differences in the ligand binding mode of the two enzymes, the first enzyme interacting mainly with substrate secondary amino groups and the second one with substrate primary amino groups. The data provide the basis for the development of novel and selective inhibitors able to discriminate between mammalian SMO and PAO activities
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.016
alpha-methylspermidine
-
addition of 5 mM benzyldehyde, hPAO
0.011 - 0.019
alpha-methylspermine
0.0027
N1,N11-diacetylnorspermine
-
-
0.0021 - 0.028
N1-acetylspermidine
0.00085 - 0.0011
N1-acetylspermine
0.015
spermidine
-
addition of 5 mM benzyldehyde, hPAO
0.0093 - 0.047
spermine
additional information
additional information
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.415
N1,N11-bis(ethyl)-norspermine
Mus musculus
-
pH 7.6, 30°C
19
N1,N11-diacetylnorspermine
Homo sapiens
-
-
1.93
N1,N12-bis(ethyl)-spermine
Mus musculus
-
pH 7.6, 30°C
4.85 - 15
N1-acetylspermidine
4.53 - 31.7
N1-acetylspermine
0.0004 - 0.175
spermine
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.008
1,12-diaminododecane
-
pH 7.5, 25°C
0.00045
guazatine
-
pH 7.5, 25°C
0.021
MDL72527
-
pH 7.5, 25°C
0.0008
N-prenylagmatine
-
pH 7.5, 25°C
0.07
N8-acetylspermine
-
-
1
putrescine
-
-
0.19
spermidine
-
-
0.75
spermine
-
-
additional information
additional information
-
inhibition kinetics, pH-dependence, overview
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.5 - 10
-
the rate constant for the reaction of the reduced enzyme with oxygen is not affected by a pH between 7.5 and 10
8
-
assay at
9
-
assay at
9.9 - 10.5
-
substrate-dependent
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 11
-
pH profile, overview
additional information
-
effects of pH on the steady-state and reductive half-reaction. Kinetics for N1-acetylspermine, N1-acetylspermidine, and spermine kcat/K(amine)-pH profiles are bell-shaped
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
20
-
assay at
37
-
assay at
pI VALUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
4.84
-
calculated from sequence
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
reduced level of PAO in neoplastic tissue
Manually annotated by BRENDA team
-
androgen-treated and untreated prostate adenocarcinoma cells
Manually annotated by BRENDA team
-
reduced level of PAO in neoplastic tissue
Manually annotated by BRENDA team
-
reduced level of PAO in neoplastic tissue
Manually annotated by BRENDA team
additional information
-
APAO is constitutively expressed in various tissues
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
55000
-
x * 55000, calculated from sequence
56101
-
x * 56101, holoenzyme (FAD-containig), calculated from sequence
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
recombinant enzyme
recombinant; recombinant enzyme
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cDNA is transiently transfected into HEK-293 cells
-
expression in Escherichia coli
-
expression in HEK-293 cells
-
expression of recombinant enzyme
-
stable expression of hPAO-1 in A549 cell line
-
transfection of A-549 cell
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
K315M
-
mutation has no effect on the kcat/Kamine profile for spermine. The kred value with N1-acetylspermine is 1.8fold lower in the mutant protein, and the pKa in the k(red)-pH profile with N1-acetylspermine shifts to 7.8. K315 does not play a critical role in amine oxidation by PAO; site-directed mutagenesis, the mutant shows altered kinetics compared to the wild-type enzyme
Y430F
-
mutation results in a 6fold decrease in the kcat value and the kcat/Km value for oxygen due to a comparable decrease in the rate constant for flavin reduction
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
medicine
-
high expression of APAO in A549 cells inhibits accumulation of antitumor polyamine analogue, N1-cyclopropylmethyl-N11-ethylnorspermine, decreases their sensitivity to the toxicity of N1-cyclopropylmethyl-N11-ethylnorspermine and prevents N1-cyclopropylmethyl-N11-ethylnorspermine-induced apoptosis
pharmacology
-
N,N'-butanedienyl butanediamine, i.e. MDL 72527 or CPC-200, a small molecule specific inhibitor of polyamine oxidase, effectively blocks androgen-induced reactive oxygen species production in human prostate cancer cells, as well as significantly delays prostate cancer progression and death in animals developing spontaneous prostate cancer