Information on EC 1.11.1.8 - iodide peroxidase

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The expected taxonomic range for this enzyme is: Eukaryota

EC NUMBER
COMMENTARY hide
1.11.1.8
-
RECOMMENDED NAME
GeneOntology No.
iodide peroxidase
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
2 iodide + H2O2 + 2 H+ = diiodine + 2 H2O
show the reaction diagram
(1)
-
-
-
2 [thyroglobulin]-3,5-diiodo-L-tyrosine + H2O2 = [thyroglobulin]-L-thyroxine + [thyroglobulin]-aminoacrylate + 2 H2O
show the reaction diagram
(4)
-
-
-
[thyroglobulin]-3-iodo-L-tyrosine + iodide + H2O2 = [thyroglobulin]-3,5-diiodo-L-tyrosine + 2 H2O
show the reaction diagram
(3)
-
-
-
[thyroglobulin]-3-iodo-L-tyrosine + [thyroglobulin]-3,5-diiodo-L-tyrosine + H2O2 = [thyroglobulin]-3,5,3'-triiodo-L-thyronine + [thyroglobulin]-aminoacrylate + 2 H2O
show the reaction diagram
(5)
-
-
-
[thyroglobulin]-L-tyrosine + iodide + H2O2 = [thyroglobulin]-3-iodo-L-tyrosine + 2 H2O
show the reaction diagram
(2)
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
iodination
-
-
-
-
oxidation
-
-
-
-
peroxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Metabolic pathways
-
-
thyroid hormone biosynthesis
-
-
Tyrosine metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
iodide:hydrogen-peroxide oxidoreductase
Thyroid peroxidase catalyses the biosynthesis of the thyroid hormones L-thyroxine and triiodo-L-thyronine. It catalyses both the iodination of tyrosine residues in thyroglobulin (forming mono- and di-iodinated forms) and their coupling to form either L-thyroxine or triiodo-L-thyronine.
CAS REGISTRY NUMBER
COMMENTARY hide
9031-28-1
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
-
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
metabolism
-
the enzyme catalyzes the transfer of iodine to thyroglobulin during thyroid hormone synthesis
physiological function
thyroid peroxidase is the key enzyme involved in thyroid hormone synthesis
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3,3',5,5'-tetramethylbenzidine + H2O2
?
show the reaction diagram
-
-
-
-
?
3,3'-dimethoxybenzidine + H2O2
?
show the reaction diagram
-
-
-
-
?
3,3'-dimethylbenzidine + H2O2
?
show the reaction diagram
-
-
-
-
?
benzidine + H2O2
?
show the reaction diagram
-
-
-
-
?
biochanin A + H2O2 + I-
6,8-diiodobiochanin A + H2O
show the reaction diagram
-
-
-
?
Br- + H2O2 + thymol blue
?
show the reaction diagram
-
ordered two-substrate mechanism
-
-
?
Br- + H2O2 + thymol blue
dibromothymolsulfonphthalein + ?
show the reaction diagram
-
-
-
-
?
diiodotyrosine + H2O2 + I-
?
show the reaction diagram
-
-
-
-
?
guaiacol + H2O2 + H+
3,3'-dimethoxy-4,4'-biphenochinone + H2O
show the reaction diagram
-
-
-
-
?
guaiacol + H2O2 + I-
tetraguaiacol + H2O
show the reaction diagram
I- + H2O2
triiodide + ?
show the reaction diagram
-
-
-
-
?
I- + H2O2 + thymol blue
diiodothymolsulfonphthalein + ?
show the reaction diagram
-
-
-
-
?
iodide + H2O2
iodine + H2O
show the reaction diagram
monoiodotyrosine + H2O2 + I-
monoiodotyrosine + diiodotyrosine + H2O
show the reaction diagram
-
-
90% diiodotyrosine, 6% monoiodotyrosine, determined using radioactive I-
?
o-dianisidine
?
show the reaction diagram
-
-
-
-
?
tyrosine + H2O2 + I-
monoiodotyrosine + diiodotyrosine + H2O
show the reaction diagram
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
iodide + H2O2
iodine + H2O
show the reaction diagram
additional information
?
-
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
protoheme
-
-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1-Methyl-2-mercaptoimidazole
-
competitive with iodide
2,2',4,4'-tetrahydroxybenzophenone
-
inhibits enzyme activity by more than 60% from 0.00001 to 0.1 mM
3,4,5-hydroxybenzoic acid propyl ester
-
mixed type inhibition
3-methylcholanthrene
-
-
Aminotriazole
arsenic trioxide
-
0.1 ppm arsenic trioxide has no effect on TPO activity, incubation for 2 min in the presence of 1.0, 5.0, or 10 ppm arsenic trioxide inhibits TPO activity to 4%, 9%, and 9% of control, respectively. After 10 min incubation in the presence of 1.0 or 5.0 ppm arsenic trioxide, TPO activity returns to 92% and 54% of control, respectively, while the presence of 10 ppm arsenic trioxide further inhibits TPO activity to 1% of control
benzhydrol
-
reduces the enzyme activity by about 30% from 0.01 to 0.1 mM
benzo(e)pyrene
-
-
benzo(k)fluoranthene
-
-
benzophenone
-
-
benzophenone 2
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inactivation is prevented by iodideone of the most potent inhibitors of TPO
bisphenol A
-
-
cyanide
cysteine
-
complete inhibition at 0.05 mM, reversible by increasing I- concentration
F21388
-
-
fisetin
-
-
genistein
-
inhibits enzyme activity by about 40% at 0.001 and 0.01 mM
glutathione
heptachlor
-
weakly inhibits the enzyme activity by about 50% at 0.01 mM
histidine
-
-
Iodide
-
above 0.1 mM at pH 5, no inhibition at pH 7
kaempferol
-
-
mearnsitrin
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IC50: 0.00197 mM. Flavonoid from aqueous partition of Myrcia uniflora. Indiscriminated consumption of Myrcia uniflora pharmaceutical products allied to the nutritional deficiency of iodine might contribute to the development of hypothyroidism and goiter
methimazol
-
-
Methimazole
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enzyme activity is reduced by more than 70% by 0.1 and 1 mM
methionine
-
complete inhibition at 0.05 mM, reversible by increasing I- concentration
morin
-
-
myricetin
-
non competitive with I-
Myricitrin
-
IC50: 0.00188 mM. Flavonoid from aqueous partition of Myrcia uniflora. Indiscriminated consumption of Myrcia uniflora pharmaceutical products allied to the nutritional deficiency of iodine might contribute to the development of hypothyroidism and goiter
naringenin
-
non competitive with I-, competitive with H2O2
p-Aminobenzoic acid
-
-
perfluorooctane sulfonate
-
-
Perfluorooctanoic acid
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slight inhibition at 0.01 mM
phenylalanine
-
-
propylthiouracil
-
-
pyrene
-
-
quercetin
-
-
resorcinol
-
-
rutin
-
-
sulfathiazole
-
-
sunitinib
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sunitinib is a tyrosine kinase inhibitor with antitumor and antiangiogenic effects. Its antithyroid effect appears to be inhibition of peroxidase
Thiocyanate
-
competitive with iodide
thiouracil
Thiourea
tryptophan
-
complete inhibition at 0.05 mM, reversible by increasing I- concentration
tyrosine
-
-
additional information
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2,2'-dihydroxy-4-methoxy benzophenone
-
increases the enzyme activity by about 1.5fold
-
2,4-dihydroxy benzophenone
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increases the enzyme activity by about 1.5fold
dibenzo(a,h)anthracene
-
2fold activation between 0.01 and 0.1 mM
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.166
3,3',5,5'-tetramethylbenzidine
-
pH 5.5
0.058
3,3'-dimethoxybenzidine
-
pH 5.5
0.177
3,3'-dimethylbenzidine
-
pH 5.5
0.049
benzidine
-
pH 5.5
22
Br-
-
; in phosphate buffer (100 mM, pH 8.0), at 20°C
0.034
H2O2
-
-
0.18 - 7.7
I-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
34.6
3,3',5,5'-tetramethylbenzidine
Homo sapiens
-
pH 5.5
11.9
3,3'-dimethoxybenzidine
Homo sapiens
-
pH 5.5
27.5
3,3'-dimethylbenzidine
Homo sapiens
-
pH 5.5
6
benzidine
Homo sapiens
-
pH 5.5
71
Br-
Ascophyllum nodosum
-
; in phosphate buffer (100 mM, pH 8.0), at 20°C
75
I-
Ascophyllum nodosum
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in phosphate buffer (100 mM, pH 8.0), at 20°C
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0009
3,4,5-hydroxybenzoic acid propyl ester
-
-
0.001 - 0.008
azide
-
depending on substrate
0.009
cyanide
-
-
0.006
kaempferol
-
-
0.013
morin
-
-
0.001
myricetin
-
-
0.007
naringenin
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00197
mearnsitrin
Homo sapiens
-
IC50: 0.00197 mM. Flavonoid from aqueous partition of Myrcia uniflora. Indiscriminated consumption of Myrcia uniflora pharmaceutical products allied to the nutritional deficiency of iodine might contribute to the development of hypothyroidism and goiter
0.00188
Myricitrin
Homo sapiens
-
IC50: 0.00188 mM. Flavonoid from aqueous partition of Myrcia uniflora. Indiscriminated consumption of Myrcia uniflora pharmaceutical products allied to the nutritional deficiency of iodine might contribute to the development of hypothyroidism and goiter
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
32
-
purified enzyme
138
-
purified enzyme with guaiacol as substrate
381
-
purified enzyme with guaiacol as substrate
464
-
with guaiacol as substrate
additional information
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7
-
iodide oxidation
7.4
-
guaiacol oxidation
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
2.5 - 7.5
-
20% of activity at pH 2.5, 70% at pH 7.5
5 - 7
-
activity independent of pH
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
IL-1alpha/IFNgamma-induced down-regulation of thyroperoxidase is not affected by Th3 cytokines
Manually annotated by BRENDA team
-
IL-1alpha/IFNgamma-induced down-regulation of thyroperoxidase is not affected by Th3 cytokines
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
-
-
Manually annotated by BRENDA team
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lesion, negative correlation between thyroperoxidase and dual oxidase H2O2-generating activities
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
in Graves‘ disease, the nuclear envelope, enlarged rough endoplasmic reticulum, and apical vesicles are strongly TPO positive
Manually annotated by BRENDA team
-
wild-type enzyme and mutant enzymes G614A, G1687T, 1808-13del, C2083, G2401A
Manually annotated by BRENDA team
-
of Graves‘ disease thyroid, enzyme is absent in the microvilli in multinodular goiter
Manually annotated by BRENDA team
-
in the perinodular normal tissue the enzyme is detected mainly in the nuclear envelope, rough endoplasmic reticulum, and subapical vesicles. In cells from Hashimoto‘s thyroiditis detected in scarce rough endoplasmic reticulum. In Graves‘ disease, the nuclear envelope, enlarged rough endoplasmic reticulum, and apical vesicles are strongly TPO positive
Manually annotated by BRENDA team
-
in Graves' disease, the nuclear envelope, enlarged rough endoplasmic reticulum, and apical vesicles are strongly TPO positive, in the perinodular normal tissue the enzyme is detected mainly in the nuclear envelope, rough endoplasmic reticulum, and subapical vesicles
Manually annotated by BRENDA team
additional information
-
in the perinodular normal tissue the enzyme is absent in the apical surface, enzyme from multinodular goiter is absent in the microvilli
-
Manually annotated by BRENDA team
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
64000
-
gel filtration, analytical ultracentrifugation
71000
-
HPLC gel filtration
91000
-
native enzyme, SDS-PAGE, double band of MW 94000
94000
-
native enzyme, SDS-PAGE, double band of MW 91000
96000
-
recombinant enzyme, SDS-PAGE, double band of MW 99000
97000
-
SDS-PAGE, double band with 105000 species
99000
-
recombinant enzyme, SDS-PAGE, double band of MW 96000
100000
105000
135000
-
gel filtration, Triton solubilized enzyme
220000 - 240000
-
the high-molecular weight-thyroid peroxidase is in the 220000-240000 Da range, SDS-PAGE
additional information
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
glycoprotein
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
20 - 25
-
stable at room temperature at pH 4 for 40 min
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
sensitive to pronase treatment
-
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-18°C, 4 months, ability of the protein to interact with autoantibodies is decreased by 20%
-
-20°C, 4 years, no loss of activity
-
-20°C, 6-12 months, no loss of activity
-
-70°C, 50 mM Tris-HCl, 0.15 M NaCl, pH 8.5, 0.1% deoxycholate
-
-70°C, several months, no loss of activity of partially purified enzyme
-
–18°C or -4°C, enzyme retains its immunoreactivity
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
; ammonium sulfate precipitation and phenyl-Sepharose column chromatography
-
partial
-
recombinant enzyme
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
CHO-K1 cells introduced with mutated TPO-MRNA
-
expressed in CHO cells
-
expressed in FTC-238 cells
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expressed in High Five cells, active enzyme
-
expressed in High Five cells, activity similar to native enzyme when grown in presence of delta-aminolevulinic acid, enzyme in supernatant
-
expressed in High Five cells, enzyme insoluble and inactive
-
expressed in insect cells and in Chinese hamster ovary cells, activity detected when grown in presence of hematin or hemin
-
expressed in Sf9 cells, no activity when grown in serum free medium, active when grown in medium containing 10% fetal calf serum and 1 mg/l haematin
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expression in Chinese hamster ovary (CHO) cells
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stable expression of mutant enzymes at the surface of CHO cells
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
thyroid-stimulating hormone (10 mUI/ml, for 24 h) does not affect TPO mRNA level
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D358A
-
mutation at position 358 led to a loss of the binding of human anti-TPO autoantibodies as efficient as a mutation of the entire region 353–363
D574/L575del
-
expressed to some extent on the cell surface, prolongation in kinetics, increasing interaction with calnexin
G533C
-
expressed to some extent on the cell surface, prolongation in kinetics, increasing interaction with calnexin
G771R
-
expressed to some extent on the cell surface, prolongation in kinetics, increasing interaction with calnexin
Q446H
-
the mutation is associated with the occurrence of congenital hypothyroidism
W527C
-
the mutation is associated with the occurrence of congenital hypothyroidism
W873X
-
the mutation is associated with the occurrence of congenital hypothyroidism
R479C
-
a novel hypothyroid dwarfism due to the missense mutation R479C of the thyroid peroxidase gene in the mouse
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
-
development of an ELISA system for quantitative determination of TPO in biological fluids, based on the use of an analytical pair of monoclonal antibodies, one of which is immobilized on solid phase, the other being present in solution. The use of this system made it possible to determine the biochemical characteristics of immunoaffinity chromatography of the enzyme and propose a new method for obtaining a highly purified preparation of its protein
medicine