Any feedback?
Information on EC 1.13.99.1 - inositol oxygenase and Organism(s) Sus scrofa and UniProt Accession Q8WN98
for references in articles please use BRENDA:EC1.13.99.1Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
1.13.99.1 inositol oxygenaseIUBMB Comments
An iron protein.
Specify your search results
Word Map
- 1.13.99.1
- d-glucuronate
-
glucaric
-
diiron
-
ambience
-
mixed-valent
-
four-electron
-
glucuronate-xylulose
- medicine
- diagnostics
The taxonomic range for the selected organisms is: Sus scrofa
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
myo-inositol oxygenase, miox4, inositol oxygenase, osmiox, rsor/miox, gsmiox1a, miox2, renal-specific oxidoreductase, ppmiox, mmiox, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
Inositol oxygenase
-
-
-
-
Kidney-specific protein 32
-
-
-
-
meso-Inositol oxygenase
-
-
-
-
MIOX
MOO
-
-
-
-
Myo-inositol oxygenase
Oxygenase, inositol
-
-
-
-
Renal-specific oxidoreductase
-
-
-
-
MIOX
-
-
-
-
Myo-inositol oxygenase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-, -
SYSTEMATIC NAME
IUBMB Comments
myo-Inositol:oxygen oxidoreductase
An iron protein.
CAS REGISTRY NUMBER
COMMENTARY
9029-59-8
-
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
D-chiro-inositol + O2
D-glucuronate
much less active with D-chiro-inositol than with myo-inositol
-
-
?
myo-inositol + O2
d-glucuronate
major role in pathogenesis of diabetis
-
-
?
myo-inositol + O2
D-glucuronate + H2O
highly specific for myo-inositol
-
-
?
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
myo-inositol + O2
d-glucuronate
major role in pathogenesis of diabetis
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Fe2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
palmitate
concomitant treatment with palmitate/bovine serum albumin and activators of PKA (forskolin), PDK/PI3K (insulin), and PKC (TPA) increase Miox activity. Concomitant treatment with respective inhibitors, i.e. H89 (PKA), wortmannin (PI3K), and calphostin (PKC), reduces the activity below the levels induced by palmitate/bovine serum albumin alone, confirming that fatty acid-induced activity is phosphorylation-dependent
D-cysteine
-
best activation system: 1 mM Fe(II) and 2 mM cysteine, L-cysteine can be replaced by D-cysteine, DL-penicillamine or gamma-L-glutamyl-L-cysteine
DL-Penicillamine
-
best activation system: 1 mM Fe(II) and 2 mM cysteine, L-cysteine can be replaced by D-cysteine, DL-penicillamine or gamma-L-glutamyl-L-cysteine
gamma-L-glutamyl-L-cysteine
-
best activation system: 1 mM Fe(II) and 2 mM cysteine, L-cysteine can be replaced by D-cysteine, DL-penicillamine or gamma-L-glutamyl-L-cysteine
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
myo-inositol oxygenase (MIOX) is a tubular enzyme that catabolizes myo-inositol to D-glucuronate via the glucuronate-xylulose pathway
physiological function
-
enzyme overexpression accentuates the cellular injury related to endoplasmic reticulum stress and accentuates tunicamycin-induced generation of reactive oxygen species
malfunction
following increased expression of MIOX in tubular cells under high glucose ambience, there is an accentuated perturbation in cellular redox and mitochondrial homeostasis, leading to cellular apoptosis. In addition, there is an increased synthesis of extracellular matrix proteins, reflective of tubulo-interstitial injury in diabetic nephropathy
malfunction
under high-glucose ambience, MIOX overexpression accentuates redox imbalance, perturbed NAD+/NADH ratios, increased ROS generation, depleted reduced glutathione, reduced GSH/GSSG ratio, and enhanced adaptive changes in the profile of the antioxidant defense system. These changes are also accompanied by mitochondrial dysfunctions, DNA damage and induction of apoptosis, accentuated activity of profibrogenic cytokine, and expression of fibronectin, the latter two being the major hallmarks of diabetic nephropathy. These perturbations are largely blocked by various reactive oxygen species inhibitors (Mito Q, diphenyleneiodonium chloride, and N-acetylcysteine) and MIOX/NOX4 siRNA
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). MIOX_PIG
282
0
32653
Swiss-Prot
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
32663
electrospray MS determination, gel filtration, SDS-PAGE, sedimentation equilibirum, enzyme does not undergo oligomerization in the presence of myo-inositol
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
monomer
1 * 32663, electrospray MS determination, gel filtration, SDS-PAGE, sedimentation equilibirum, enzyme does not undergo oligomerization in the presence of myo-inositol
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
under high-glucose ambience, MIOX overexpression accentuates redox imbalance, perturbed NAD+/NADH ratios, increased ROS generation, depleted reduced glutathione, reduced GSH/GSSG ratio, and enhanced adaptive changes in the profile of the antioxidant defense system. These changes are also accompanied by mitochondrial dysfunctions, DNA damage and induction of apoptosis, accentuated activity of profibrogenic cytokine, and expression of fibronectin, the latter two being the major hallmarks of diabetic nephropathy. These perturbations are largely blocked by various reactive oxygen species inhibitors (Mito Q, diphenyleneiodonium chloride, and N-acetylcysteine) and MIOX/NOX4 siRNA, overview. Cells under high glucose ambience or transfected with MIOX-pcDNA show increased expression of apoptogenic protein Bax. The expression is further increased following concomitant treatment with HG and MIOX transfection. Treatment with N-acetylcysteine reduces the expression of Bax
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
Completely active even in absence of Fe(II) and cysteine if it has been stored at -20°C for days to weeks at pH 6.0 with 1 mM glutathione
-
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C for weeks or months: activation -20°C, completely active even in absence of Fe(II) and cysteine for days to weeks at pH 6.0 with 1 mM glutathione
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
gene MIOX, quantitative real-time PCR enzyme expression analysis, overexpression of MIOX in LLC-PK1 cells boosts the generation of H2O2
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
palmitate-conjugated bovine serum albumin causes a dose-dependent increase in Miox expression and activity in LLCPK-1 cells. Concomitant with Miox upregulation, a dose-dependent increased Bax protein expression is observed following palmitate/BSA treatment of LLCPK-1 cells. Concomitant treatment with palmitate/bovine serum albumin and activators of PKA (forskolin), PDK/PI3K (insulin), and PKC (TPA) further increase Miox activity
the enzyme expression is upregulated under high glucose treatment in LLC-PK1 cells, a tubular cell line. Under high-glucose ambience, MIOX overexpression accentuates redox imbalance, perturbed NAD+/NADH ratios, increased ROS generation, depleted reduced glutathione, reduced GSH/GSSG ratio, and enhanced adaptive changes in the profile of the antioxidant defense system. These changes are also accompanied by mitochondrial dysfunctions, DNA damage and induction of apoptosis, accentuated activity of profibrogenic cytokine, and expression of fibronectin, the latter two being the major hallmarks of diabetic nephropathy. These perturbations are largely blocked by various reactive oxygen species inhibitors (Mito Q, diphenyleneiodonium chloride, and N-acetylcysteine) and MIOX/NOX4 siRNA, overview
transcriptional and translational modulation of myo-inositol oxygenase (Miox) by fatty acids, overview
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Moskala, R.; Reddy, C.C.; Minard, R.D.; Hamilton, G.A.
An oxygen-18 tracer investigation of the mechanism of myo-inositol oxygenase
Biochem. Biophys. Res. Commun.
99
107-113
1981
Sus scrofa
Reddy, C.C.; Hamilton, G.A.
Activation of homogeneous preparations of hog kidney myo-inositol oxygenase by quinolinic acid and ferrous ions
Biochem. Biophys. Res. Commun.
100
1389-1395
1981
Sus scrofa
Reddy, C.C.; Swan, J.S.; Hamilton, G.A.
myo-Inositol oxygenase from hog kidney. I. Purification and characterization of the oxygenase and of an enzyme complex containing the oxygenase and D-glucuronate reductase
J. Biol. Chem.
156
8510-8518
1981
Sus scrofa
Reddy, C.C.; Pierzchala, P.A.; Hamilton, G.A.
myo-Inositol oxygenase from hog kidney. II. Catalytic properties of the homogeneous enzyme
J. Biol. Chem.
256
8519-8524
1981
Sus scrofa
Naber, N.I.; Swan, J.S.; Hamilton, G.A.
L-myo-Inosose-1 as a probable intermediate in the reaction catalyzed by myo-inositol oxygenase
Biochemistry
25
7201-7207
1986
Sus scrofa
Arner, R.J.; Prabhu, K.S.; Thompson, J.T.; Hildenbrandt, G.R.; Liken, A.D.; Reddy, C.C.
myo-Inositol oxygenase: molecular cloning and expression of a unique enzyme that oxidizes myo-inositol and D-chiro-inositol
Biochem. J.
360
313-320
2001
Sus scrofa (Q8WN98), Sus scrofa
Arner, R.J.; Prabhu, K.S.; Krishnan, V.; Johnson, M.C.; Reddy, C.C.
Expression of myo-inositol oxygenase in tissues susceptible to diabetic complications
Biochem. Biophys. Res. Commun.
339
816-820
2006
Homo sapiens, Mus musculus, Sus scrofa
Tominaga, T.; Dutta, R.K.; Joladarashi, D.; Doi, T.; Reddy, J.K.; Kanwar, Y.S.
Transcriptional and translational modulation of myo-inositol oxygenase (Miox) by fatty acids implications in renal tubular injury induced in obesity and diabetes
J. Biol. Chem.
291
1348-1367
2016
Homo sapiens (Q9UGB7), Mus musculus (Q9QXN5), Mus musculus CD1 (Q9QXN5), Rattus norvegicus (Q9QXN4), Sus scrofa (Q8WN98)
Sun, L.; Dutta, R.K.; Xie, P.; Kanwar, Y.S.
myo-Inositol oxygenase overexpression accentuates generation of reactive oxygen species and exacerbates cellular injury following high glucose ambience a new mechanism relevant to the pathogenesis of diabetic nephropathy
J. Biol. Chem.
291
5688-5707
2016
Sus scrofa (Q8WN98)
EXTERNAL LINKS (specific for EC-Number 1.13.99.1)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
