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Information on EC 3.5.99.6 - glucosamine-6-phosphate deaminase and Organism(s) Homo sapiens
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3.5.99.6 glucosamine-6-phosphate deaminaseIUBMB Comments
The enzyme uses ring opening and isomerization of the aldose-ketose type to convert the -CH(-NH2)-CH=O group of glucosamine 6-phosphate into -C(=NH)-CH2-OH, forming 2-deoxy-2-imino-D-arabino-hexitol, which then hydrolyses to yield fructose 6-phosphate and ammonia. N-Acetyl-D-glucosamine 6-phosphate, which is not broken down, activates the enzyme.
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Word Map
- 3.5.99.6
- obesity
- n-acetylglucosamine
-
tmem18
-
kctd15
-
sec16b
-
tfap2b
-
homotropic
-
5.3.1.10
- n-acetylglucosamine-6-phosphate
- d-glucosamine
-
bmi-associated
- naga
- glcnac6p
-
glcnac-6-phosphate
-
lyplal1
-
tnni3k
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
gnpda2, glucosamine-6-phosphate deaminase, oscillin, gnpda1, gnpda, glucosamine-6-phosphate isomerase, glucosamine 6-phosphate deaminase, glcn6p deaminase, glucosamine 6-phosphate isomerase, glucosamine-6p deaminase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
2-amino-2-deoxy-D-glucose-6-phosphate ketol isomerase (deaminating)
-
-
-
-
aminodeoxyglucosephosphate isomerase
-
-
-
-
GlcN-6-P isomerase
-
-
-
-
GlcN6P deaminase
-
-
-
-
glucosamine 6-phosphate deaminase
-
-
-
-
glucosamine 6-phosphate isomerase
-
-
-
-
glucosamine phosphate deaminase
-
-
-
-
glucosamine-6-phosphate deaminase
-
-
-
-
glucosamine-P isomerase
-
-
-
-
glucosaminephosphate isomerase
-
-
-
-
GNPDA
isomerase, glucosamine phosphate
-
-
-
-
oscillin
-
-
-
-
phoshoglucosamine isomerase
-
-
-
-
phosphoglucosaminisomerase
-
-
-
-
GNPDA
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
intramolecular oxidoreduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-, -, -, -
SYSTEMATIC NAME
IUBMB Comments
2-amino-2-deoxy-D-glucose-6-phosphate aminohydrolase (ketol isomerizing)
The enzyme uses ring opening and isomerization of the aldose-ketose type to convert the -CH(-NH2)-CH=O group of glucosamine 6-phosphate into -C(=NH)-CH2-OH, forming 2-deoxy-2-imino-D-arabino-hexitol, which then hydrolyses to yield fructose 6-phosphate and ammonia. N-Acetyl-D-glucosamine 6-phosphate, which is not broken down, activates the enzyme.
CAS REGISTRY NUMBER
COMMENTARY
9013-10-9
-
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
additional information
?
-
-
the activity of the enzyme in erythrocytes is low, indicating that hexosamine catabolism is not a major source of energy in the erythrocyte
-
-
?
alpha-D-glucosamine 6-phosphate + H2O
D-fructose 6-phosphate + NH3
-
-
-
r
alpha-D-glucosamine 6-phosphate + H2O
D-fructose 6-phosphate + NH3
in standard culture conditions keratinocyte GNPDAs mainly catalyze the reaction from GlcN6P back to Fru6P
-
-
r
D-glucosamine 6-phosphate + H2O
D-fructose 6-phosphate + NH3
-
-
-
?
D-glucosamine 6-phosphate + H2O
D-fructose 6-phosphate + NH3
-
-
r
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
D-glucosamine 6-phosphate + H2O
D-fructose 6-phosphate + NH3
-
-
-
?
additional information
?
-
-
the activity of the enzyme in erythrocytes is low, indicating that hexosamine catabolism is not a major source of energy in the erythrocyte
-
-
?
alpha-D-glucosamine 6-phosphate + H2O
D-fructose 6-phosphate + NH3
-
-
-
r
alpha-D-glucosamine 6-phosphate + H2O
D-fructose 6-phosphate + NH3
in standard culture conditions keratinocyte GNPDAs mainly catalyze the reaction from GlcN6P back to Fru6P
-
-
r
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
Mn2+, Hg2+, Mg2+, Co2+ and Ni2+ enhance in decreasing order the activity in both directions
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
UDP-N-acetylglucosamine
-
slight inhibition at 1.67 mM, slight activation at 0.00167-0.167 mM
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
N-acetylglucosamine 6-phosphate
GlcNAc6P, allosteric site ligand, behaving as a V activator and a K inhibitor: in the absence of GlcNAc6P, the apparent kcat of the enzyme is so low, that GlcNAc6P behaves as an essential activator. Additionally, substrate inhibition, dependent on GlcNAc6P concentration, is observed, Monod allosteric model with some additional postulates, overview. The ligand binds to either enzyme conformational state, but with higher affinity for the R form
UDP-N-acetylglucosamine
-
slight activation at 0.00167-0.167 mM, slight inhibition at 1.67 mM
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
3.5
D-fructose 6-phosphate
-
pH 8.5, 37°C, in presence of N-acetylglucosamine 6-phosphate and Mn2+
0.25
D-glucosamine 6-phosphate
-
pH 8.5, 37°C, in presence of N-acetylglucosamine 6-phosphate and Mn2+
0.27
D-glucosamine 6-phosphate
recombinant wild-type isozyme GNPDA1, pH 8.0, 30°C, kinetic method 1, in absence of N-acetylglucosamine 6-phosphate
2
D-glucosamine 6-phosphate
recombinant isozyme GNPDA1 275 truncation mutant, pH 8.0, 30°C, kinetic method 1
16.5
D-glucosamine 6-phosphate
recombinant wild-type isozyme GNPDA1, pH 8.0, 30°C, kinetic method 1, in presence of saturating concentration of N-acetylglucosamine 6-phosphate
additional information
additional information
allosteric enzyme, hGNPDA1 enzyme displays hyperbolic kinetics but very low-activity in the absence of GlcNAc6P, kinetic analysis and modelling of both reaction directions, detailed overview
-
additional information
additional information
allosteric enzyme, hGNPDA1 enzyme displays hyperbolic kinetics but very low-activity in the absence of GlcNAc6P, kinetic analysis and modelling of both reaction directions, detailed overview
-
additional information
additional information
-
allosteric enzyme, hGNPDA1 enzyme displays hyperbolic kinetics but very low-activity in the absence of GlcNAc6P, kinetic analysis and modelling of both reaction directions, detailed overview
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
41.2
D-glucosamine 6-phosphate
recombinant isozyme GNPDA1 268 truncation mutant, pH 8.0, 30°C, kinetic method 2
44.2
D-glucosamine 6-phosphate
recombinant isozyme GNPDA1 275 truncation mutant, pH 8.0, 30°C, kinetic method 1
74
D-glucosamine 6-phosphate
recombinant isozyme GNPDA1 275 truncation mutant, pH 8.0, 30°C, kinetic method 2
228
D-glucosamine 6-phosphate
recombinant wild-type isozyme GNPDA1, pH 8.0, 30°C, kinetic method 1, in presence of saturating concentration of N-acetylglucosamine 6-phosphate
260
D-glucosamine 6-phosphate
recombinant wild-type isozyme GNPDA1, pH 8.0, 30°C, kinetic method 2, in presence of saturating concentration of N-acetylglucosamine 6-phosphate
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7 - 9.5
-
pH 7.0: about 55% of maximal activity, pH 9.5: about 74% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
hGNPDA1 can be important for the maintenance of an adequate level of the pool of the UDP-GlcNAc6P, the N-acetylglucosylaminyl donor for many reactions in the cell
additional information
malfunction
depletion of GFAT1 reduces the cellular pool of UDP-GlcNAc and hyaluronan synthesis, while simultaneous blocking of both isozymes GNPDA1 and GDPDA2 exerts opposite effects, indicating that in standard culture conditions keratinocyte GNPDAs mainly catalyze the reaction from GlcN6P back to Fru6P. When hexosamine biosynthesis is blocked by GFAT1 siRNA, the effect by GNPDAs is reversed, now catalyzing Fru6P towards GlcN6P, likely in an attempt to maintain UDPGlcNAc content. Silencing of these enzymes also changes the gene expression of related enzymes: GNPDA1 siRNA induces GFAT2 which is hardly measurable in these cells under standard culture conditions, GNPDA2 siRNA increases GFAT1, and GFAT1 siRNA increases the expression of hyaluronan synthase 2 (HAS2). Silencing of GFAT1 stimulates GNPDA1 and GDPDA2, and inhibites cell migration. The multiple delicate adjustments of these reactions demonstrate the importance of hexosamine biosynthesis in cellular homeostasis, known to be deranged in diseases like diabetes and cancer. GNPDA1 siRNA, while ineffective by itself, could largely prevent the influence of mannose on UDP-GlcNAc and hyaluronan synthesis, thus raising GNPDA1 as a specific candidate for the target of mannose. The finding that GNPDA1 siRNA does not counteract the mannose-induced depletion of cell surface hyaluronan suggests that in addition to GNPDA1 mannose may target cell surface receptor activity
malfunction
depletion of GFAT1 reduces the cellular pool of UDP-GlcNAc and hyaluronan synthesis, while simultaneous blocking of both isozymes GNPDA1 and GDPDA2 exerts opposite effects, indicating that in standard culture conditions keratinocyte GNPDAs mainly catalyze the reaction from GlcN6P back to Fru6P. When hexosamine biosynthesis is blocked by GFAT1 siRNA, the effect by GNPDAs is reversed, now catalyzing Fru6P towards GlcN6P, likely in an attempt to maintain UDPGlcNAc content. Silencing of these enzymes also changes the gene expression of related enzymes:GNPDA1 siRNA induces GFAT2 which is hardly measurable in these cells under standard culture conditions, GNPDA2 siRNA increases GFAT1, and GFAT1 siRNA increases the expression of hyaluronan synthase 2 (HAS2). Silencing of GFAT1 stimulates GNPDA1 and GDPDA2, and inhibites cell migration. The multiple delicate adjustments of these reactions demonstrate the importance of hexosamine biosynthesis in cellular homeostasis, known to be deranged in diseases like diabetes and cancer
metabolism
distinct contributions of glucosamine-6-phosphate (GlcN6P):glutamine-fructose-6-phosphate aminotransferases (GFAT1 and 2) and glucosamine-6-phosphate deaminases (GNPDA1 and 2) isozymes to the UDP-GlcNAc pool of cultured keratinocytes, and their consequences to the hyaluronan synthesis, one of the cellular processes most dependent on cytosolic UDP-GlcNAc supply, and to cell proliferation and migration, overview
metabolism
distinct contributions of glucosamine-6-phosphate (GlcN6P):glutamine-fructose-6-phosphate aminotransferases (GFAT1 and 2) and glucosamine-6-phosphate deaminases (GNPDA1 and 2)isozymes to the UDP-GlcNAc pool of cultured keratinocytes, and their consequences to the hyaluronan synthesis, one of the cellular processes most dependent on cytosolic UDP-GlcNAc supply, and to cell proliferation and migration, overview
additional information
possible functional significance of the C-terminal extension of hGNPDA1 isozyme, which is not present in isoform 2
additional information
possible functional significance of the C-terminal extension of hGNPDA1 isozyme, which is not present in isoform 2
additional information
-
possible functional significance of the C-terminal extension of hGNPDA1 isozyme, which is not present in isoform 2
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). GNPI1_HUMAN
289
0
32669
Swiss-Prot
other Location (Reliability: 2)
GNPI2_HUMAN
276
0
31085
Swiss-Prot
other Location (Reliability: 2)
D6R917_HUMAN
138
0
15911
TrEMBL
other Location (Reliability: 2)
D6RB13_HUMAN
160
0
18218
TrEMBL
other Location (Reliability: 2)
A0A024R9X5_HUMAN
276
0
31085
TrEMBL
other Location (Reliability: 2)
D6RAY7_HUMAN
237
0
26987
TrEMBL
other Location (Reliability: 2)
D6R9P4_HUMAN
274
0
30900
TrEMBL
other Location (Reliability: 2)
B3KMV2_HUMAN
255
0
28641
TrEMBL
other Location (Reliability: 2)
D6RFF8_HUMAN
290
0
32381
TrEMBL
other Location (Reliability: 2)
A8K3S1_HUMAN
289
0
32679
TrEMBL
other Location (Reliability: 2)
PDB
SCOP
CATH
UNIPROT
ORGANISM
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
isozyme GNPDA1, X-ray diffraction structure determination and analysis at 1.75 A resolution
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
generation of mutants truncated at positions 260 and 275
additional information
generation of mutants truncated at positions 260 and 275
additional information
-
generation of mutants truncated at positions 260 and 275
additional information
siRNA silencing of isozymes GNPDA1 and GDPDA2 with or withour simultanious silencing of glucosamine-6-phosphate (GlcN6P): glutamine-fructose-6-phosphate aminotransferases (GFAT1 and 2) isozymes, phenotypes, overview. Analysis of influences of the siRNAs against genes regulating hexosamine biosynthesis on mRNA levels of GFAT1, GNPDA1, and GNPDA2 by quantitative RT-PCR expression analysis. Cell proliferation and migration following GFAT and GNPDA depletion
additional information
siRNA silencing of isozymes GNPDA1 and GDPDA2 with or withour simultanious silencing of glucosamine-6-phosphate (GlcN6P): glutamine-fructose-6-phosphate aminotransferases (GFAT1 and 2) isozymes, phenotypes, overview. Analysis of influences of the siRNAs against genes regulating hexosamine biosynthesis on mRNA levels of GFAT1, GNPDA1, and GNPDA2 by quantitative RT-PCR expression analysis. Cell proliferation and migration following GFAT and GNPDA depletion
additional information
-
siRNA silencing of isozymes GNPDA1 and GDPDA2 with or withour simultanious silencing of glucosamine-6-phosphate (GlcN6P): glutamine-fructose-6-phosphate aminotransferases (GFAT1 and 2) isozymes, phenotypes, overview. Analysis of influences of the siRNAs against genes regulating hexosamine biosynthesis on mRNA levels of GFAT1, GNPDA1, and GNPDA2 by quantitative RT-PCR expression analysis. Cell proliferation and migration following GFAT and GNPDA depletion
additional information
siRNA silencing of isozymes GNPDA1 and GDPDA2 with or without simultanious silencing of glucosamine-6-phosphate (GlcN6P):glutamine-fructose-6-phosphate aminotransferases (GFAT1 and 2) isozymes, phenotypes, overview. Analysis of influences of the siRNAs against genes regulating hexosamine biosynthesis on mRNA levels of GFAT1, GNPDA1, and GNPDA2 by quantitative RT-PCR expression analysis. Cell proliferation and migration following GFAT and GNPDA depletion. GNPDA1 siRNA, while ineffective by itself, can largely prevent the influence of mannose on UDP-GlcNAc and hyaluronan synthesis, thus raising GNPDA1 as a specific candidate for the target of mannose. The finding that GNPDA1 siRNA does not counteract the mannose-induced depletion of cell surface hyaluronan suggests that in addition to GNPDA1 mannose may target cell surface receptor activity
additional information
siRNA silencing of isozymes GNPDA1 and GDPDA2 with or without simultanious silencing of glucosamine-6-phosphate (GlcN6P):glutamine-fructose-6-phosphate aminotransferases (GFAT1 and 2) isozymes, phenotypes, overview. Analysis of influences of the siRNAs against genes regulating hexosamine biosynthesis on mRNA levels of GFAT1, GNPDA1, and GNPDA2 by quantitative RT-PCR expression analysis. Cell proliferation and migration following GFAT and GNPDA depletion. GNPDA1 siRNA, while ineffective by itself, can largely prevent the influence of mannose on UDP-GlcNAc and hyaluronan synthesis, thus raising GNPDA1 as a specific candidate for the target of mannose. The finding that GNPDA1 siRNA does not counteract the mannose-induced depletion of cell surface hyaluronan suggests that in addition to GNPDA1 mannose may target cell surface receptor activity
additional information
-
siRNA silencing of isozymes GNPDA1 and GDPDA2 with or without simultanious silencing of glucosamine-6-phosphate (GlcN6P):glutamine-fructose-6-phosphate aminotransferases (GFAT1 and 2) isozymes, phenotypes, overview. Analysis of influences of the siRNAs against genes regulating hexosamine biosynthesis on mRNA levels of GFAT1, GNPDA1, and GNPDA2 by quantitative RT-PCR expression analysis. Cell proliferation and migration following GFAT and GNPDA depletion. GNPDA1 siRNA, while ineffective by itself, can largely prevent the influence of mannose on UDP-GlcNAc and hyaluronan synthesis, thus raising GNPDA1 as a specific candidate for the target of mannose. The finding that GNPDA1 siRNA does not counteract the mannose-induced depletion of cell surface hyaluronan suggests that in addition to GNPDA1 mannose may target cell surface receptor activity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant isozyme GNPDA1 from Escherichia coli strain IBPC 590 by single purification step by means of allosteric-site affinity chromatography on N-6-aminohexanoyl-GlcN6P agarose
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of isozyme GNPDA1 in Escherichia coli strain IBPC 590 (DELTAnagEBACD DELTAlac), which carries a deletion of the chromosomal copy of the nag operon and expresses the recombinant enzyme constitutively from the lac promoter due to the lacI mutation
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Pattabiraman, T.N.; Bachhawat, B.K.
Purification of glucosamine 6-phosphate deaminase from human brain
Biochim. Biophys. Acta
54
273-283
1961
Homo sapiens
Weidanz, J.A.; Campbell, P.; DeLucas, L.J.; Jin, J.; Moore, D.; Roden, L.; Yu, H.; Heilmann, E.; Vezza, A.C.
Glucosamine 6-phosphate deaminase in normal human erythrocytes
Br. J. Haematol.
91
72-79
1995
Homo sapiens
Arreola, R.; Valderrama, B.; Morante, M.L.; Horjales, E.
Two mammalian glucosamine-6-phosphate deaminases: a structural and genetic study
FEBS Lett.
551
63-70
2003
Mus musculus, Homo sapiens (P46926), Homo sapiens
Alvarez-Anorve, L.I.; Alonzo, D.A.; Mora-Lugo, R.; Lara-Gonzalez, S.; Bustos-Jaimes, I.; Plumbridge, J.; Calcagno, M.L.
Allosteric kinetics of the isoform 1 of human glucosamine-6-phosphate deaminase
Biochim. Biophys. Acta
1814
1846-1853
2011
Homo sapiens (P46926), Homo sapiens (Q8TDQ7), Homo sapiens
Oikari, S.; Makkonen, K.; Deen, A.J.; Tyni, I.; Kaernae, R.; Tammi, R.H.; Tammi, M.I.
Hexosamine biosynthesis in keratinocytes roles of GFAT and GNPDA enzymes in the maintenance of UDP-GlcNAc content and hyaluronan synthesis
Glycobiology
26
710-722
2016
Homo sapiens (P46926), Homo sapiens (Q8TDQ7), Homo sapiens
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