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Information on EC 1.1.1.8 - glycerol-3-phosphate dehydrogenase (NAD+) and Organism(s) Homo sapiens and UniProt Accession P21695
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1.1.1.8 glycerol-3-phosphate dehydrogenase (NAD+)IUBMB Comments
Also acts on propane-1,2-diol phosphate and glycerone sulfate (but with a much lower affinity).
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Word Map
- 1.1.1.8
- adipose
- adipocytes
- dhap
-
preadipocytes
-
alpha-gpdh
-
3-phosphatase
-
phosphodianion
-
fad-linked
- synthesis
- food industry
- nutrition
- medicine
- biotechnology
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
Synonyms
glycerol 3-phosphate dehydrogenase, mgpdh, gpdh-1, glycerol-3-phosphate dehydrogenase 1, gpd1p, g3p dehydrogenase, cgpdh, gpdh-2, cggpd, alpha glycerophosphate dehydrogenase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
alpha-glycerol phosphate dehydrogenase (NAD)
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alpha-glycerophosphate dehydrogenase (NAD)
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dehydrogenase, glycerol phosphate
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glycerol 1-phosphate dehydrogenase
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-
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glycerol phosphate dehydrogenase (NAD)
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glycerophosphate dehydrogenase (NAD)
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-
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hydroglycerophosphate dehydrogenase
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L-alpha-glycerol phosphate dehydrogenase
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L-alpha-glycerophosphate dehydrogenase
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L-glycerol phosphate dehydrogenase
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L-glycerophosphate dehydrogenase
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NAD-alpha-glycerophosphate dehydrogenase
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NAD-dependent glycerol phosphate dehydrogenase
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-
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NAD-dependent glycerol-3-phosphate dehydrogenase
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NAD-L-glycerol-3-phosphate dehydrogenase
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NAD-linked glycerol 3-phosphate dehydrogenase
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NADH-dihydroxyacetone phosphate reductase
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
sn-glycerol 3-phosphate + NAD+ = glycerone phosphate + NADH + H+
one active site per enzyme molecule
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
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oxidation
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-
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reduction
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PATHWAY SOURCE
PATHWAYS
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-, -, -
SYSTEMATIC NAME
IUBMB Comments
sn-glycerol-3-phosphate:NAD+ 2-oxidoreductase
Also acts on propane-1,2-diol phosphate and glycerone sulfate (but with a much lower affinity).
CAS REGISTRY NUMBER
COMMENTARY
9075-65-4
-
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
dihydroxyacetone phosphate + NADH
sn-glycerol 3-phosphate + NAD+
an electrophilic catalytic mechanism by the epsilon-NH3+ group of Lys204 is proposed on the basis of the structural analysis
-
-
?
dihydroxyacetone phosphate + NADH + H+
sn-glycerol 3-phosphate + NAD+
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-
-
-
r
additional information
?
-
-
involved in cellular acidosis, oxidoresistance, apoptosis by both acidosis and cell-cell contact inhibition, cell growth, and the generation of recombinant proteins
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-
?
sn-glycerol 3-phosphate + NAD+
dihydroxyacetone phosphate + NADH + H+
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-
-
?
sn-glycerol 3-phosphate + NAD+
dihydroxyacetone phosphate + NADH + H+
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-
-
?
sn-glycerol 3-phosphate + NAD+
dihydroxyacetone phosphate + NADH + H+
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-
-
r
sn-glycerol 3-phosphate + NAD+
dihydroxyacetone phosphate + NADH + H+
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equilibrium far to the side of alpha-glycerophosphate at neutral pH
-
?
sn-glycerol 3-phosphate + NAD+
dihydroxyacetone phosphate + NADH + H+
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mGPDH is involved in maintaining a high rate of glycolysis and is an important site of electron leakage leading to production of reactive oxygen species in prostate cancer cells
-
-
?
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
additional information
?
-
-
involved in cellular acidosis, oxidoresistance, apoptosis by both acidosis and cell-cell contact inhibition, cell growth, and the generation of recombinant proteins
-
-
?
sn-glycerol 3-phosphate + NAD+
dihydroxyacetone phosphate + NADH + H+
-
-
-
?
sn-glycerol 3-phosphate + NAD+
dihydroxyacetone phosphate + NADH + H+
-
-
-
r
sn-glycerol 3-phosphate + NAD+
dihydroxyacetone phosphate + NADH + H+
-
equilibrium far to the side of alpha-glycerophosphate at neutral pH
-
?
sn-glycerol 3-phosphate + NAD+
dihydroxyacetone phosphate + NADH + H+
-
mGPDH is involved in maintaining a high rate of glycolysis and is an important site of electron leakage leading to production of reactive oxygen species in prostate cancer cells
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
phosphite dianion
strongly inhibits the mutant N270A enzyme. The N270A mutation results in a change in the effect of phosphite dianion on (kcat/Km)obs for GPDH-catalyzed reduction of glycerone phosphate, from strongly activating to inhibiting
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
phosphite dianion
strongly activates the wild-type enzyme. The N270A mutation results in a change in the effect of phosphite dianion on (kcat/Km)obs for GPDH-catalyzed reduction of glycerone phosphate, from strongly activating to inhibiting
glycerol
-
competitive activator with respect to dihydroxyacetone phosphate above 30 mM
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
15
dihydroxyacetone phosphate
mutant enzyme R269A/N270A, at pH 7.5 and 25°C
additional information
additional information
Michaelis-Menten kinetics
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00028
dihydroxyacetone phosphate
mutant enzyme R269A/N270A, at pH 7.5 and 25°C
0.0059
dihydroxyacetone phosphate
mutant enzyme R269A, at pH 7.5 and 25°C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.17
dihydroxyacetone phosphate
mutant enzyme R269A/N270A, at pH 7.5 and 25°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.7 - 8.7
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about 80% of maximal activity at pH 6.7 and 8.7, reduction of dihydroxyacetone phosphate, decrease of activity below and above these pH values
8.1 - 9.4
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about 80% of maximal activity at pH 8.1 and 9.4, oxidation of glycerol-3-phosphate, decrease of activity below and rapidly above these pH values
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
mGPDH abundance and activity is significantly elevated in prostate cancer cell lines when compared to the normal prostate epithelial cell line PNT1A
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mGPDH abundance and activity is significantly elevated in prostate cancer cell lines when compared to the normal prostate epithelial cell line PNT1A
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mGPDH abundance and activity is significantly elevated in prostate cancer cell lines when compared to the normal prostate epithelial cell line PNT1A
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mGPDH abundance and activity is significantly elevated in prostate cancer cell lines when compared to the normal prostate epithelial cell line PNT1A
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mGPDH abundance and activity is significantly elevated in prostate cancer cell lines when compared to the normal prostate epithelial cell line PNT1A
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
mutation N270A results in a 7.7 kcal/mol decrease in the intrinsic phosphodianion binding energy, which is larger than the 5.6 kcal/mol effect of the mutation on the stability of the transition state for reduction of DHAP. A 2.2 kcal/mol stabilization of the transition state for unactivated hydride transfer to the truncated substrate glycolaldehyde, and a change in the effect of phosphite dianion on GPDH-catalyzed reduction of glycolaldehyde, from strongly activating to inhibiting. The N270A mutation breaks the network of hydrogen bonding side chains, Asn270, Thr264, Asn205, Lys204, Asp260, and Lys120, which connect the dianion activation and catalytic sites of GPDH. The disruption dramatically alters the performance of GPDH at these sites
physiological function
additional information
physiological function
role for Asn270 in glycerol 3-phosphate dehydrogenase-catalyzed hydride transfer
physiological function
exogenous expression of GPD1 in human MCF-7 and MDA-MB-231 breast cancer cells significantly inhibits cell proliferation, migration, and invasion
additional information
-
structure-function analysis of wild-type and mutant enzymes, overview
additional information
structure-function analysis of wild-type and mutant enzymes, overview
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). GPDA_HUMAN
349
0
37568
Swiss-Prot
other Location (Reliability: 4)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
hanging-drop vapor-diffusion method enzyme/NAD+ complex, enzyme/dihydroxyacetonephosphate complex, enzyme/NAD+/dihydroxyacetonephosphate complex
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
N270A
site-direted mutagenesis, the mutation results in a 7.7 kcal/mol decrease in the intrinsic phosphodianion binding energy, which is larger than the 5.6 kcal/mol effect of the mutation on the stability of the transition state for reduction of DHAP. A 2.2 kcal/mol stabilization of the transition state for unactivated hydride transfer to the truncated substrate glycolaldehyde, and a change in the effect of phosphite dianion on GPDH-catalyzed reduction of glycolaldehyde, from strongly activating to inhibiting. The N270A mutation breaks the network of hydrogen bonding side chains, Asn270, Thr264, Asn205, Lys204, Asp260, and Lys120, which connect the dianion activation and catalytic sites of GPDH. The disruption dramatically alters the performance of GPDH at these sites. The mutant enzyme shows highly decreased activity compared to the wild-type with glycerone phosphate,but 40fold higher activity with glycolaldehyde compared to the wild-type. There is no significant rescue of the activity of the N270A mutant with glycerone phosphate by 60 mM formamide
R269A
site-direted mutagenesis, the mutant enzyme shows highly reduced activity compared to the wild-type
R269A/N270A
site-direted mutagenesis, the mutant enzyme shows reduced activity compared to the wild-type. The N270A mutation at R269A hlGPDH results in the loss of the intrinsic side chain-dianion interaction
N270A
the mutant shows a strong decrease in catalytic efficiency compared to the wild type enzyme
R269A
R269A/N270A
the mutant shows a strong decrease in catalytic efficiency compared to the wild type enzyme
R269A
the mutant shows a strong decrease in catalytic efficiency compared to the wild type enzyme
R269A
-
the mutant shows no detectable activity toward reduction of glycolaldehyde
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Escherichia coli BL-21 DE3 as a fusion protein with glutathione S-transferase
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
the mRNA expression level of glycerol-3-phosphate dehydrogenase (GPD1) is significantly downregulated in human breast cancer patients. Patients with reduced GPD1 expression exhibit poorer overall metastatic relapse-free survival. The reduced expression of GPD1 is an independent predictor of overall survival in oestrogen receptor-positive and nodal-negative breast cancer patients. GPD1 is a direct target of miR-370, which is significantly upregulated in human breast cancer. Exogenous expression of GPD1 in MCF-7 and MDA-MB-231 breast cancer cells significantly inhibits cell proliferation, migration, and invasion
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Baranowski, T.
alpha-Glycerophosphate dehydrogenase
The Enzymes, 2nd Ed. (Boyer, P. D. , Lardy, H. , Myrbck, K. , eds. )
7
85-96
1963
Bos taurus, Oryctolagus cuniculus, Homo sapiens, Locusta migratoria, Mus musculus, Rattus norvegicus
-
Zolnierowicz, S.; Swierczynski, J.; Zelewski, L.
Isolation and properties of glycerol-3-phosphate oxidoreductase from human placenta
Eur. J. Biochem.
154
161-166
1986
Homo sapiens
Koekemoer, T.C.; Litthauer, D.; Oelofsen, W.
Isolation and characterization of adipose tissue glycerol-3-phasphate dehydrogenase
Int. J. Biochem. Cell Biol.
27
625-632
1995
Homo sapiens
Chowdhury, S.K.; Gemin, A.; Singh, G.
High activity of mitochondrial glycerophosphate dehydrogenase and glycerophosphate-dependent ROS production in prostate cancer cell lines
Biochem. Biophys. Res. Commun.
333
1139-1145
2005
Homo sapiens
Ou, X.; Ji, C.; Han, X.; Zhao, X.; Li, X.; Mao, Y.; Wong, L.L.; Bartlam, M.; Rao, Z.
Crystal structures of human glycerol 3-phosphate dehydrogenase 1 (GPD1)
J. Mol. Biol.
357
858-869
2006
Homo sapiens (P21695), Homo sapiens
Jeong, D.W.; Cho, I.T.; Kim, T.S.; Bae, G.W.; Kim, I.H.; Kim, I.Y.
Effects of lactate dehydrogenase suppression and glycerol-3-phosphate dehydrogenase overexpression on cellular metabolism
Mol. Cell. Biochem.
284
1-8
2006
Homo sapiens
Reyes, A.C.; Amyes, T.L.; Richard, J.P.
Enzyme architecture: a startling role for Asn270 in glycerol 3-phosphate dehydrogenase-catalyzed hydride transfer
Biochemistry
55
1429-1432
2016
Homo sapiens, Homo sapiens (P21695)
Reyes, A.C.; Amyes, T.L.; Richard, J.P.
Structure-reactivity effects on intrinsic primary kinetic isotope effects for hydride transfer catalyzed by glycerol-3-phosphate dehydrogenase
J. Am. Chem. Soc.
138
14526-14529
2016
Homo sapiens
Reyes, A.C.; Amyes, T.L.; Richard, J.P.
Enzyme architecture: self-assembly of enzyme and substrate pieces of glycerol-3-phosphate dehydrogenase into a robust catalyst of hydride transfer
J. Am. Chem. Soc.
138
15251-15259
2016
Homo sapiens
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