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Information on EC 1.1.5.3 - glycerol-3-phosphate dehydrogenase and Organism(s) Mus musculus and UniProt Accession Q64521
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1.1.5.3 glycerol-3-phosphate dehydrogenaseIUBMB Comments
This flavin-dependent dehydrogenase is an essential membrane enzyme, functioning at the central junction of glycolysis, respiration and phospholipid biosynthesis. In bacteria, the enzyme is localized to the cytoplasmic membrane , while in eukaryotes it is tightly bound to the outer surface of the inner mitochondrial membrane . In eukaryotes, this enzyme, together with the cytosolic enzyme EC 1.1.1.8, glycerol-3-phosphate dehydrogenase (NAD+), forms the glycerol-3-phosphate shuttle by which NADH produced in the cytosol, primarily from glycolysis, can be reoxidized to NAD+ by the mitochondrial electron-transport chain . This shuttle plays a critical role in transferring reducing equivalents from cytosolic NADH into the mitochondrial matrix [7,8]. Insect flight muscle uses only CoQ10 as the physiological quinone whereas hamster and rat mitochondria use mainly CoQ9 . The enzyme is activated by calcium .
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Word Map
- 1.1.5.3
- adipocytes
- adipose
-
preadipocytes
-
adipogenesis
- triglyceride
- lipase
-
proliferator-activated
- lipoprotein
-
adipogenic
- succinate
- obesity
- pancreatic
- dihydroxyacetone
- glucose-6-phosphate
- leptin
- islet
- dexamethasone
- malate
-
droplet
-
1.1.1.8
- hexokinase
- triacylglycerols
-
confluence
-
serum-free
-
malic
-
stromal-vascular
- sn-glycerol-3-phosphate
- dhap
-
depots
-
perirenal
- adipsin
- triiodothyronine
-
lipolysis
-
non-insulin-dependent
- adiponectin
-
differentiation-dependent
-
anti-obesity
- receptor-gamma
-
protein-alpha
- alpha-glycerophosphate
-
nad-linked
- dunaliella
-
antiadipogenic
- glycerokinase
-
ppargamma2
-
preadipose
-
adipocyte-specific
-
omental
- glycosomes
-
malate-aspartate
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
glycerol-3-phosphate dehydrogenase, glycerophosphate dehydrogenase, mitochondrial glycerol-3-phosphate dehydrogenase, sn-glycerol 3-phosphate dehydrogenase, glycerol-3-phosphate dehydrogenase 2, fad-linked glycerol-3-phosphate dehydrogenase, fad-gpdh, fad-dependent glycerol-3-phosphate dehydrogenase, mitochondrial sn-glycerol 3-phosphate dehydrogenase, glycerol-3-phosphate oxidoreductase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
PATHWAY SOURCE
PATHWAYS
-
-, -, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
sn-glycerol 3-phosphate:quinone oxidoreductase
This flavin-dependent dehydrogenase is an essential membrane enzyme, functioning at the central junction of glycolysis, respiration and phospholipid biosynthesis. In bacteria, the enzyme is localized to the cytoplasmic membrane [6], while in eukaryotes it is tightly bound to the outer surface of the inner mitochondrial membrane [2]. In eukaryotes, this enzyme, together with the cytosolic enzyme EC 1.1.1.8, glycerol-3-phosphate dehydrogenase (NAD+), forms the glycerol-3-phosphate shuttle by which NADH produced in the cytosol, primarily from glycolysis, can be reoxidized to NAD+ by the mitochondrial electron-transport chain [3]. This shuttle plays a critical role in transferring reducing equivalents from cytosolic NADH into the mitochondrial matrix [7,8]. Insect flight muscle uses only CoQ10 as the physiological quinone whereas hamster and rat mitochondria use mainly CoQ9 [4]. The enzyme is activated by calcium [3].
CAS REGISTRY NUMBER
COMMENTARY
9001-49-4
-
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
sn-glycerol 3-phosphate + menadione
glycerone phosphate + reduced menadione
-
-
-
?
additional information
?
-
usage of an assay method specific for superoxide/H2O2 production by mGPDH
-
-
?
sn-glycerol 3-phosphate + ubiquinone
glycerone phosphate + ubiquinol
-
-
-
ir
sn-glycerol 3-phosphate + ubiquinone
glycerone phosphate + ubiquinol
the ubiquinone-linked reaction catalyzed by mGPDH is irreversible
-
-
ir
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
sn-glycerol 3-phosphate + ubiquinone
glycerone phosphate + ubiquinol
-
-
-
ir
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4-[4-(1H-benzimidazol-2-yl)anilino]-4-oxobutanoic acid
mixed type inhibition, potent and selective inhibitor
4-[4-(1H-naphtho[2,3-d]imidazol-2-yl)anilino]-4-oxobutanoic acid
mixed type inhibition
4-[4-[5-(3-carboxypropanamido)-1H-benzimidazol-2-yl]anilino]-4-oxobutanoic acid
-
4-[4-[5-(cyclohexa-2,4-diene-1-carbonyl)-1H-benzimidazol-2-yl]anilino]-4-oxobutanoic acid
-
glyceraldehyde 3-phosphate
about 80% inhibition at 2.5 mM, glyceraldehyde 3-phosphate is not a specific inhibitor of mGPDH but also alters succinate oxidation
additional information
screening and identification of cell-permeant small-molecule inhibitors of mGPDH (iGP) discovered through small-molecule screening. Structure-activity analysis identifies a core benzimidazole-phenyl-succinamide structure as being essential to inhibition of mGPDH while modifications to the benzimidazole ring system modulate both potency and off-target effects. The iGPs penetrate cellular membranes. Inhibitor selectivity, and effects of the inhibitors on kinetics of mGPDH, overview
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
the calcium-sensitive EF-hand domain of the enzyme lowers the Km for glycerol 3-phosphate as physiological levels of free calcium rise
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0095
4-[4-(1H-benzimidazol-2-yl)anilino]-4-oxobutanoic acid
pH not specified in the publication, 37°C
0.0007
4-[4-(1H-naphtho[2,3-d]imidazol-2-yl)anilino]-4-oxobutanoic acid
pH not specified in the publication, 37°C
additional information
additional information
inhibition kinetics of iGP-1 and iGP-5
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.05
4-[3-(1H-benzimidazol-2-yl)anilino]-4-oxobutanoic acid
Mus musculus
pH not specified in the publication, 37°C
0.015
4-[4-(1,3-benzothiazol-2-yl)anilino]-4-oxobutanoic acid
Mus musculus
pH not specified in the publication, 37°C
0.02
4-[4-(1,3-benzoxazol-2-yl)anilino]-4-oxobutanoic acid
Mus musculus
pH not specified in the publication, 37°C
0.0063 - 0.008
4-[4-(1H-benzimidazol-2-yl)anilino]-4-oxobutanoic acid
Mus musculus
pH not specified in the publication, 37°C
0.0007 - 0.001
4-[4-(1H-naphtho[2,3-d]imidazol-2-yl)anilino]-4-oxobutanoic acid
Mus musculus
pH not specified in the publication, 37°C
0.005
4-[4-(5-methyl-1H-benzimidazol-2-yl)anilino]-4-oxobutanoic acid
Mus musculus
pH not specified in the publication, 37°C
0.003
4-[4-[5-(cyclohexa-2,4-diene-1-carbonyl)-1H-benzimidazol-2-yl]anilino]-4-oxobutanoic acid
Mus musculus
pH not specified in the publication, 37°C
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
glycerol-3-phosphate dehydrogenase protein levels and enzyme activity are highest in brown adipose tissue
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
the active site of mGPDH faces the mitochondrial intermembrane space, as does its calcium-sensitive EF-hand domain
nuclear-encoded enzyme associated with the inner mitochondrial membrane
the enzyme is localized to the outer membrane of the mitochondria facing the cytoplasm
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
physiological function
malfunction
in the absence of Gpd2, hyperactivation and acrosome reaction are significantly altered, and a few changes in protein tyrosine phosphorylation are observed during sperm capacitation. The testicular size of Gpd2-deficient animals is about 10% smaller than in wild type animals. Gpd2-null animals show a 4% reduction in tubular diameter and about 10% reduction in numbers of both spermatocytes and spermatids per seminiferous tubule
malfunction
despite the widespread expression of the enzyme, mGPDH-knockout mice display relatively mild phenotypes beyond weaning. These include decreased body mass and decreased white fat mass
physiological function
GPD2 enables tyrosine phosphorylation during sperm capacitation. GPD2 activity is required for reactive oxygen species generation in mouse spermatozoa during capacitation
physiological function
mitochondrial sn-glycerol 3-phosphate dehydrogenase (mGPDH) is a ubiquinone-linked enzyme in the mitochondrial inner membrane best characterized as part of the glycerol phosphate shuttle that transfers reducing equivalents from cytosolic NADH into the mitochondrial electron transport chain
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). GPDM_MOUSE
727
1
80954
Swiss-Prot
Mitochondrion (Reliability: 5)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoprotein
GPD2 is tyrosine phosphorylated only in capacitated spermatozoa of wild type mice
ubiquitination
mitochondrial sn-glycerol 3-phosphate dehydrogenase is a ubiquinone-linked enzyme
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Koza, R.A.; Kozak, U.C.; Brown, L.J.; Leiter, E.H.; MacDonald, M.J.; Kozak, L.P.
Sequence and tissue-dependent RNA expression of mouse FAD-linked glycerol-3-phosphate dehydrogenase
Arch. Biochem. Biophys.
336
97-104
1996
Mus musculus (Q64521), Mus musculus
Kota, V.; Rai, P.; Weitzel, J.M.; Middendorff, R.; Bhande, S.S.; Shivaji, S.
Role of glycerol-3-phosphate dehydrogenase 2 in mouse sperm capacitation
Mol. Reprod. Dev.
77
773-783
2010
Mus musculus (Q64521), Mus musculus
Sato, T.; Morita, A.; Mori, N.; Miura, S.
The role of glycerol-3-phosphate dehydrogenase 1 in the progression of fatty liver after acute ethanol administration in mice
Biochem. Biophys. Res. Commun.
444
525-530
2014
Mus musculus
Orr, A.L.; Ashok, D.; Sarantos, M.R.; Ng, R.; Shi, T.; Gerencser, A.A.; Hughes, R.E.; Brand, M.D.
Novel inhibitors of mitochondrial sn-glycerol 3-phosphate dehydrogenase
PLoS ONE
9
e89938
2014
Rattus norvegicus (P35571), Mus musculus (Q64521), Mus musculus C57BL/6 (Q64521), Rattus norvegicus Wistar (P35571)
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