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Information on EC 1.11.1.8 - iodide peroxidase
for references in articles please use BRENDA:EC1.11.1.8
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EC Tree 1 Oxidoreductases
1.11 Acting on a peroxide as acceptor
1.11.1 Peroxidases
1.11.1.8 iodide peroxidase
IUBMB Comments
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.
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
- 1.11.1.8
- thyroglobulin
- tsh
- autoimmune
- hypothyroidism
- autoantibody
- thyroxin
- women
- graves
-
tpoabs
- hashimoto
- thyrotropin
-
thyroid-stimulating
- pregnancy
-
subclinical
-
euthyroidism
- triiodothyronine
- goiter
-
follicular
-
overt
- thyrocytes
-
anti-tpo
-
antithyroid
-
symporter
-
organification
-
trimester
- levothyroxine
- autoantigens
-
thyroid-specific
-
frtl-5
- guaiacol
- methimazole
- lactoperoxidase
-
radioiodine
- propylthiouracil
-
goitrous
- thyrotoxicosis
-
antibody-negative
-
multinodular
- analysis
-
peroxidase-catalyzed
-
hypothalamic-pituitary-thyroid
-
ophthalmopathy
-
gadas
-
tsh-induced
-
anti-thyroglobulin
- medicine
-
thyroid-associated
-
tsh-stimulated
- chloroperoxidase
- synthesis
- nodosum
- haloperoxidases
-
thyrotoxic
Reaction Schemes
show2
+
=
+
+
2
2
+
=
+
+
2
Synonyms
thyroid peroxidase, thyroperoxidase, bromoperoxidase, vanadium bromoperoxidase, iodide peroxidase, hrtpo, iodinase, hmw-tpo, tyrosine iodinase, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
iodide peroxidase-tyrosine iodinase
-
-
-
-
iodinase
-
-
-
-
iodoperoxidase (heme type)
-
-
-
-
thyroid peroxidase
thyroperoxidase
TPO
tyrosine iodinase
-
-
-
-
thyroid peroxidase
-
-
-
-
thyroid peroxidase
-
-
thyroperoxidase
-
-
-
-
TPO
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2 iodide + H2O2 + 2 H+ = diiodine + 2 H2O
(1)
-
-
-
2 [thyroglobulin]-3,5-diiodo-L-tyrosine + H2O2 = [thyroglobulin]-L-thyroxine + [thyroglobulin]-aminoacrylate + 2 H2O
(4)
-
-
-
[thyroglobulin]-3-iodo-L-tyrosine + iodide + H2O2 = [thyroglobulin]-3,5-diiodo-L-tyrosine + 2 H2O
(3)
-
-
-
[thyroglobulin]-3-iodo-L-tyrosine + [thyroglobulin]-3,5-diiodo-L-tyrosine + H2O2 = [thyroglobulin]-3,5,3'-triiodo-L-thyronine + [thyroglobulin]-aminoacrylate + 2 H2O
(5)
-
-
-
[thyroglobulin]-L-tyrosine + iodide + H2O2 = [thyroglobulin]-3-iodo-L-tyrosine + 2 H2O
(2)
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
iodination
-
-
-
-
oxidation
-
-
-
-
peroxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
BRENDA
KEGG
MetaCyc
thyroid hormone biosynthesis
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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.
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CAS REGISTRY NUMBER
COMMENTARY
9031-28-1
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
Br- + H2O2 + thymol blue
?
-
Substrates: ordered two-substrate mechanism
Products: -
Products: -
?
Br- + H2O2 + thymol blue
dibromothymolsulfonphthalein + ?
-
Substrates: -
Products: -
Products: -
?
guaiacol + H2O2 + H+
3,3'-dimethoxy-4,4'-biphenoquinone + H2O
-
Substrates: -
Products: -
Products: -
?
I- + H2O2 + thymol blue
diiodothymolsulfonphthalein + ?
-
Substrates: -
Products: -
Products: -
?
monoiodotyrosine + H2O2 + I-
monoiodotyrosine + diiodotyrosine + H2O
-
Substrates: -
Products: 90% diiodotyrosine, 6% monoiodotyrosine, determined using radioactive I-
Products: 90% diiodotyrosine, 6% monoiodotyrosine, determined using radioactive I-
?
guaiacol + H2O2
3,3'-dimethoxy-4,4'-biphenoquinone + H2O
-
Substrates: -
Products: -
Products: -
?
guaiacol + H2O2
3,3'-dimethoxy-4,4'-biphenoquinone + H2O
Substrates: -
Products: -
Products: -
?
guaiacol + H2O2 + I-
tetraguaiacol + H2O
-
Substrates: -
Products: -
Products: -
?
guaiacol + H2O2 + I-
tetraguaiacol + H2O
-
Substrates: -
Products: -
Products: -
?
iodide + H2O2
iodine + H2O
-
Substrates: iodination and coupling reactions of proteins
Products: -
Products: -
?
iodide + H2O2
iodine + H2O
-
Substrates: iodination and coupling reactions of proteins
Products: -
Products: -
?
iodide + H2O2
iodine + H2O
-
Substrates: biosynthesis of thyroid hormones
Products: -
Products: -
?
iodide + H2O2
iodine + H2O
-
Substrates: -
Products: -
Products: -
?
iodide + H2O2
iodine + H2O
-
Substrates: biosynthesis of thyroid hormones
Products: -
Products: -
?
iodide + H2O2
iodine + H2O
-
Substrates: autoantigenin autoimmune thyroid disease
Products: -
Products: -
?
iodide + H2O2
iodine + H2O
-
Substrates: iodination and coupling reactions of proteins
Products: -
Products: -
?
iodide + H2O2
iodine + H2O
-
Substrates: highest activity if coupled with glucose-glucose oxidase reaction for H2O2 production
Products: -
Products: -
?
iodide + H2O2
iodine + H2O
-
Substrates: iodination and coupling reactions of proteins
Products: -
Products: -
?
tyrosine + H2O2 + I-
monoiodotyrosine + diiodotyrosine + H2O
-
Substrates: -
Products: ratio 1:4
Products: ratio 1:4
?
tyrosine + H2O2 + I-
monoiodotyrosine + diiodotyrosine + H2O
-
Substrates: -
Products: -
Products: -
?
additional information
?
-
-
Substrates: amino acids from TPO region 713-717 are the key residues, recognized by IDR/B-specific anti-TPO autoantibodies in autoimmune thyroid disease
Products: -
Products: -
?
additional information
?
-
-
Substrates: several changes in ultracytochemical characteristics of the enzyme are associated with thyroid disease
Products: -
Products: -
?
additional information
?
-
-
Substrates: H353, D358, S359 and R361 are amino acid residues contributing to the binding of anti-TPO autoantibodies in the immunodominant regions
Products: -
Products: -
?
additional information
?
-
-
Substrates: protein radical formation on thyroid peroxidase during turnover
Products: -
Products: -
?
additional information
?
-
-
Substrates: hypothyroid dwarfism due to the missense mutation R479C of the thyroid peroxidase gene in the mouse
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
iodide + H2O2
iodine + H2O
-
Substrates: iodination and coupling reactions of proteins
Products: -
Products: -
?
iodide + H2O2
iodine + H2O
-
Substrates: iodination and coupling reactions of proteins
Products: -
Products: -
?
iodide + H2O2
iodine + H2O
-
Substrates: biosynthesis of thyroid hormones
Products: -
Products: -
?
iodide + H2O2
iodine + H2O
-
Substrates: biosynthesis of thyroid hormones
Products: -
Products: -
?
iodide + H2O2
iodine + H2O
-
Substrates: autoantigenin autoimmune thyroid disease
Products: -
Products: -
?
iodide + H2O2
iodine + H2O
-
Substrates: iodination and coupling reactions of proteins
Products: -
Products: -
?
iodide + H2O2
iodine + H2O
-
Substrates: iodination and coupling reactions of proteins
Products: -
Products: -
?
additional information
?
-
-
Substrates: amino acids from TPO region 713-717 are the key residues, recognized by IDR/B-specific anti-TPO autoantibodies in autoimmune thyroid disease
Products: -
Products: -
?
additional information
?
-
-
Substrates: several changes in ultracytochemical characteristics of the enzyme are associated with thyroid disease
Products: -
Products: -
?
additional information
?
-
-
Substrates: hypothyroid dwarfism due to the missense mutation R479C of the thyroid peroxidase gene in the mouse
Products: -
Products: -
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
heme
-
heme prosthetic group of TPO is stable and gives a A412/A280ratio of 0.38
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
benzophenone 2
-
inactivation is prevented by iodideone of the most potent inhibitors of TPO
cysteine
-
complete inhibition at 0.05 mM, reversible by increasing I- concentration
mearnsitrin
-
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
methionine
-
complete inhibition at 0.05 mM, reversible by increasing I- concentration
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
reduced glutathione
-
presence of 0.1 ppm minimally affects enzyme activity. Presence of 0.1 ppm arsenic trioxide plus 0.1 ppm reduced glutathione leads to complete inhibition
sunitinib
-
sunitinib is a tyrosine kinase inhibitor with antitumor and antiangiogenic effects. Its antithyroid effect appears to be inhibition of peroxidase
TR1.9 autoantibody
preferentially binds the TPO monomer and inhibits the catalytic activity
-
tryptophan
-
complete inhibition at 0.05 mM, reversible by increasing I- concentration
2,2',4,4'-tetrahydroxybenzophenone
-
inhibits enzyme activity by more than 60% from 0.00001 to 0.1 mM
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
arsenic trioxide
-
presence of 0.1 ppm minimally affects enzyme activity. Presence of 0.1 ppm arsenic trioxide plus 0.1 ppm reduced glutathione leads to complete inhibition
rutin
competitive, rutin and quercetin as well as rutin and rosmarinic acid act additively
additional information
-
no inhibition with sulfhydryl reacting reagents and p-chloromercuribenzoate
-
additional information
-
inhibited by hydrolyzed enzyme preparation, hydrolyzed bovine serum albumin and casein, guaiacol oxidation not significantly affected by amino acids
-
additional information
-
CHO cells cultured in methimazole for days show a 58-82% reduction in high molecular weight-thyroid peroxidase isoforms at methimazole concentrations of 0.001-0.5 mM, whereas monomeric thyroid peroxidase expression is unchanged. A similar reduction in thyroid peroxidase expression (34-74%) is observed in CHO cells cultured in propylthiouracil (0.01-0.5 mM)
-
additional information
-
2,3,4-trihydroxybenzophenone, 2,4,4'-trihydroxybenzophenone, 4-hydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, chrysene, naphthalene, benzo(a)anthracene, phenanthrene, hexachlorobenzene, mirex, chlordane, and methylmercury have no effect on enzyme activity
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2,2'-dihydroxy-4-methoxy benzophenone
-
increases the enzyme activity by about 1.5fold
cumin ethanol extract
activating, and also acts as effective lipoxygenase inhibitor
-
green coffee ethanol extract
activating, and also acts as effective lipoxygenase inhibitor
-
green tea ethanol extract
activating, and also acts as effective lipoxygenase inhibitor
-
mustard ethanol extract
activating, and also acts as effective lipoxygenase inhibitor
-
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
5.55
guaiacol
wild-type, pH 7.4, temperature not specified in the publication
7.03
guaiacol
mutant G387R, pH 7.4, temperature not specified in the publication
7.39
guaiacol
mutant P499L, pH 7.4, temperature not specified in the publication
9.67
guaiacol
mutant C808R, pH 7.4, temperature not specified in the publication
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
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
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
180