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L-lysine + 2-oxoglutarate + NADH
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
-
-
-
r
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH
-
-
-
r
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH + H+
L-lysine + 2-oxoglutarate + NADH
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
-
-
-
-
?
L-lysine + 2-oxoglutarate + NADH + H+
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + alpha-ketoadipate + NADH
?
-
-
-
-
?
L-lysine + alpha-ketobutyrate + NADH
?
-
-
-
-
?
L-lysine + alpha-ketomalonate + NADH
?
-
-
-
-
?
L-lysine + alpha-ketovalerate + NADH
?
-
-
-
-
?
L-lysine + glyoxylate + NADH
?
-
-
-
-
?
L-lysine + pyruvate + NADH
?
-
-
-
-
?
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH + H+
additional information
?
-
-
3-acetylpyridine adenine dinucleotide, 3-pyridinealdehyde adenine dinucleotide, and thionicotinamide adenine dinucleotide can serve as a substrate in the oxidative deamination reaction, as can glyoxylate, pyruvate, alpha-ketobutyrate, alpha-ketovalerate, alpha-ketomalonate, and alpha-ketoadipate in the reverse reaction
-
-
?
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH + H+
-
-
-
?
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH + H+
-
-
-
r
L-lysine + 2-oxoglutarate + NADH + H+
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
-
-
-
-
?
L-lysine + 2-oxoglutarate + NADH + H+
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
-
-
-
-
r
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH
-
-
-
-
?
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH
-
-
-
-
r
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH
-
high specificity with respect to coenzyme and substrate
-
-
?
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH
-
high specificity with respect to coenzyme and substrate
-
r
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH
-
A-stereospecific in hydrogen transfer in the synthesis of saccharopine from alpha-ketoglutarate and L-lysine
-
-
?
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH
-
i.e. saccharopine
-
r
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH
-
i.e. saccharopine
-
r
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH
-
involved in lysine biosynthesis
-
-
?
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH
-
last step of alpha-aminoadipate pathway for lysine biosynthesis
-
-
?
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH + H+
-
-
-
-
?
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH + H+
-
-
-
-
r
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH + H+
-
the enzyme is specific for L-lysine
-
-
r
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L-lysine + 2-oxoglutarate + NADH
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
-
-
-
r
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH + H+
-
-
-
r
L-lysine + 2-oxoglutarate + NADH + H+
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
-
-
-
-
r
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH + H+
-
-
-
-
r
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH
-
-
-
-
?
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH
-
-
-
-
r
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH
-
involved in lysine biosynthesis
-
-
?
N6-(L-1,3-dicarboxypropyl)-L-lysine + NAD+ + H2O
L-lysine + 2-oxoglutarate + NADH
-
last step of alpha-aminoadipate pathway for lysine biosynthesis
-
-
?
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0.11 - 267
2-oxoglutarate
5.3
alpha-ketoadipate
-
at pH 7.0
153
alpha-Ketobutyrate
-
at pH 7.0
24
alpha-ketomalonate
-
at pH 7.0
94
alpha-ketovalerate
-
at pH 7.0
6.4
glyoxylate
-
at pH 7.0
0.2 - 14
N6-(L-1,3-dicarboxypropyl)-L-lysine
additional information
additional information
-
detailed kinetic analysis including pH-dependance and deuterium kinetic effects
-
0.11
2-oxoglutarate
wild type enzyme, in 100 mM HEPES, pH 7.0, at 25°C
9
2-oxoglutarate
mutant enzyme H96Q, in 100 mM HEPES, pH 7.0, at 25°C
10
2-oxoglutarate
mutant enzyme K77M, in 100 mM HEPES, pH 7.0, at 25°C
267
2-oxoglutarate
mutant enzyme K77M/H96Q, in 100 mM HEPES, pH 7.0, at 25°C
0.89
L-lysine
wild type enzyme, in 100 mM HEPES, pH 7.0, at 25°C
25
L-lysine
mutant enzyme K77M, in 100 mM HEPES, pH 7.0, at 25°C
96
L-lysine
mutant enzyme K77M/H96Q, in 100 mM HEPES, pH 7.0, at 25°C
267
L-lysine
mutant enzyme H96Q, in 100 mM HEPES, pH 7.0, at 25°C
0.11
2-oxoglutarate
-
at pH 7.0
0.11
2-oxoglutarate
-
wild type enzyme, at pH 7.0 and 25°C
0.11
2-oxoglutarate
-
wild-type, 25°C, pH 7.2
0.11
2-oxoglutarate
-
mutant enzyme C205S, at pH 7.0 and 25°C
0.18
2-oxoglutarate
-
mutant E78A, 25°C, pH 7.2
0.23
2-oxoglutarate
-
mutant E78Q, 25°C, pH 7.2
0.3
2-oxoglutarate
-
mutant E122Q, 25°C, pH 7.2
0.38
2-oxoglutarate
-
mutant enzyme C205V, at pH 7.0 and 25°C
0.55
2-oxoglutarate
-
mutant E122A, 25°C, pH 7.2
2
2-oxoglutarate
-
mutant E78Q/E122Q, 25°C, pH 7.2
4.8 - 5
2-oxoglutarate
-
mutant E78A/E122A, 25°C, pH 7.2
0.62
L-lysine
-
mutant E78A, 25°C, pH 7.2
0.89
L-lysine
-
mutant enzyme C205S, at pH 7.0 and 25°C
1.1
L-lysine
-
25°C, pH 7.0
1.1
L-lysine
-
wild type enzyme, at pH 7.0 and 25°C
1.1
L-lysine
-
wild-type, 25°C, pH 7.2
3
L-lysine
-
mutant enzyme C205V, at pH 7.0 and 25°C
4
L-lysine
-
mutant E78Q, 25°C, pH 7.2
11
L-lysine
-
mutant E122Q, 25°C, pH 7.2
27.1
L-lysine
-
mutant E78Q/E122Q, 25°C, pH 7.2
36.5
L-lysine
-
mutant E122A, 25°C, pH 7.2
190.7
L-lysine
-
mutant E78A/E122A, 25°C, pH 7.2
0.2
N6-(L-1,3-dicarboxypropyl)-L-lysine
-
mutant enzyme C205S, at pH 7.0 and 25°C
1.4
N6-(L-1,3-dicarboxypropyl)-L-lysine
-
mutant enzyme C205V, at pH 7.0 and 25°C
2
N6-(L-1,3-dicarboxypropyl)-L-lysine
-
mutant E78Q, 25°C, pH 7.2
6.7
N6-(L-1,3-dicarboxypropyl)-L-lysine
-
25°C, pH 7.0
6.7
N6-(L-1,3-dicarboxypropyl)-L-lysine
-
wild type enzyme, at pH 7.0 and 25°C
6.7
N6-(L-1,3-dicarboxypropyl)-L-lysine
-
wild-type, 25°C, pH 7.2
14
N6-(L-1,3-dicarboxypropyl)-L-lysine
-
mutant E122Q, 25°C, pH 7.2
0.1
NAD+
-
-
0.9
NAD+
-
wild type enzyme, at pH 7.0 and 25°C
0.9
NAD+
-
wild-type, 25°C, pH 7.2
1.1
NAD+
-
mutant E78Q, 25°C, pH 7.2
1.2
NAD+
-
mutant enzyme C205V, at pH 7.0 and 25°C
1.8
NAD+
-
mutant enzyme C205S, at pH 7.0 and 25°C
3.3
NAD+
-
mutant E122Q, 25°C, pH 7.2
0.01
NADH
-
mutant enzyme C205S, at pH 7.0 and 25°C
0.014
NADH
-
mutant E78Q, 25°C, pH 7.2
0.019
NADH
-
25°C, pH 7.0
0.019
NADH
-
wild type enzyme, at pH 7.0 and 25°C
0.019
NADH
-
wild-type, 25°C, pH 7.2
0.025
NADH
-
mutant E122Q, 25°C, pH 7.2
0.036
NADH
-
mutant E78A, 25°C, pH 7.2
0.05
NADH
-
mutant enzyme C205V, at pH 7.0 and 25°C
0.062
NADH
-
mutant E122A, 25°C, pH 7.2
0.12
NADH
-
mutant E78Q/E122Q, 25°C, pH 7.2
0.133
NADH
-
mutant E78A/E122A, 25°C, pH 7.2
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H96Q
the mutation results in 100 and more than 1000fold increases in Km values for L-lysine and 2-oxoglutarate, respectively
K77M
the mutation results in 28 and 90fold increases in Km values for L-lysine and 2-oxoglutarate, respectively
K77M/H96Q
the mutations result in 300 and 80fold increases in Km values for L-lysine and 2-oxoglutarate, respectively
C205S
-
the Km for N6-(L-1,3-dicarboxypropyl)-L-lysine decreases by more than 30fold for the C205S mutant
C205V
-
the Km for N6-(L-1,3-dicarboxypropyl)-L-lysine decreases by 5fold for the C205V mutant
E122A
-
mutation increases the positive charge of the active site and affects the pKa value of the catalytic group. Kinetic mechanism similar to wild-type
E122Q
-
mutation increases the positive charge of the active site and affects the pKa value of the catalytic group. Kinetic mechanism similar to wild-type
E16Q/C205S
-
the mutation decreases the turnover number by about 15fold
E78A
-
mutation increases the positive charge of the active site and affects the pKa value of the catalytic group. Kinetic mechanism differs from wild-type, 2-oxoglutarate binds to enzyme and enzyme-NADH
E78A/E122A
-
mutation increases the positive charge of the active site and affects the pKa value of the catalytic group. Kinetic mechanism similar to wild-type
E78Q
-
mutation increases the positive charge of the active site and affects the pKa value of the catalytic group. Kinetic mechanism similar to wild-type
E78Q/E122Q
-
mutation increases the positive charge of the active site and affects the pKa value of the catalytic group. Kinetic mechanism similar to wild-type
K13M/C205S
-
the mutation decreases the turnover number by about 15fold
additional information
generation of a mdh3/gpd1DELTA double mutant that accumulates saccharopine and displays lysine bradytrophy. Lysine biosynthesis is restored when saccharopine dehydrogenase is mislocalised to the cytosol in mdh3/gpd1DELTA cells. Recombinantly expressed GFP-tagged Lys1p colocalizes with the peroxisomal marker HcRed-PTS1 in glucose-grown cells. A disruption of the peroxisomal NAD+/NADH ratio as a consequence of a block in the redox shuttles leads to an increase in the Lys1p substrate/product ratio. The saccharopine/lysine ratio increases in mdh3/gpd1DELTA cells by more than 80fold. When Lys1p is mislocalised to the cytosol in mdh3/gpd1DELTA cells, the cytosolic pool of NAD+ supports Lys1p activity and lysine biosynthesis is restored. A decrease of saccharopine dehydrogenase activity (Lys1p-activity) causes lysine bradytrophy in mdh3/gpd1DELTA cells
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Saunders, P.P.; Broquist, H.P.
Saccharopine, an intermediate of the aminoadipic acid pathway of lysine biosynthesis. IV. Saccharopine dehydrogenase
J. Biol. Chem.
241
3435-3440
1966
Saccharomyces cerevisiae
brenda
Fujioka, M.
Chemical mechanism of saccharopine dehydrogenase (NAD+, L-lysine-forming) as deduced from initial rate pH studies
Arch. Biochem. Biophys.
230
553-559
1984
Saccharomyces cerevisiae
brenda
Fujioka, M.
Active-site residues of saccharopine dehydrogenase (NAD+, lysine-forming) from bakers yeast
Biochem. Soc. Trans.
9
281-282
1981
Saccharomyces cerevisiae
brenda
Fujioka, M.; Takata, Y.
Role of arginine residue in saccharopine dehydrogenase (L-lysine forming) from bakers yeast
Biochemistry
20
468-472
1981
Saccharomyces cerevisiae
brenda
Ogawa, H.; Fujioka, M.
The reaction of pyridoxal 5-phosphate with an essential lysine residue of saccharopine dehydrogenase (L-lysine-forming)
J. Biol. Chem.
255
7420-7425
1980
Saccharomyces cerevisiae
brenda
Fujioka, M.; Takata, Y.; Ogawa, H.; Okamoto, M.
The inactivation of saccharopine dehydrogenase (L-lysine-forming) by diethyl pyrocarbonate
J. Biol. Chem.
255
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1980
Saccharomyces cerevisiae
brenda
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Stereospecificity of hydrogen transfer in the saccharopine dehydrogenase reaction
Biochim. Biophys. Acta
570
210-212
1979
Saccharomyces cerevisiae
brenda
Ogawa, H.; Okamoto, M.; Fujioka, M.
Chemical modification of the active site sulfhydryl group of saccharopine dehydrogenase (L-lysine-forming)
J. Biol. Chem.
254
7030-7035
1979
Saccharomyces cerevisiae
brenda
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The reaction of pyruvate with saccharopine dehydrogenase
Eur. J. Biochem.
90
301-307
1978
Saccharomyces cerevisiae
brenda
Ogawa, H.; Fujioka, M.
Purification and characterization of saccharopine dehydrogenase from bakers yeast
J. Biol. Chem.
253
3666-3670
1978
Saccharomyces cerevisiae
brenda
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Saccharopine dehydrogenase. Substrate inhibition studies
J. Biol. Chem.
250
8986-8989
1975
Saccharomyces cerevisiae
brenda
Fujioka, M.; Nakatani, Y.
Saccharopine dehydrogenase. A kinetic study of coenzyme binding
J. Biol. Chem.
249
6886-6891
1974
Saccharomyces cerevisiae
brenda
Fujioka, M.; Nakatani, Y.
Saccharopine dehydrogenase. Interaction with substrate analogues
Eur. J. Biochem.
25
301-307
1972
Saccharomyces cerevisiae
brenda
Fujioka, M.; Nakatani, Y.
A kinetic study of saccharopine dehydrogenase reaction
Eur. J. Biochem.
16
180-186
1970
Saccharomyces cerevisiae
brenda
Broquist, H.P.
Saccharopine dehydrogenase
Methods Enzymol.
17B
124-129
1971
Saccharomyces cerevisiae
-
brenda
Xu, H.; West, A.H.; Cook, P.F.
Overall kinetic mechanism of saccharopine dehydrogenase from Saccharomyces cerevisiae
Biochemistry
45
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2006
Saccharomyces cerevisiae
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Xu, H.; Alguindigue, S.S.; West, A.H.; Cook, P.F.
A proposed proton shuttle mechanism for saccharopine dehydrogenase from Saccharomyces cerevisiae
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46
871-882
2007
Saccharomyces cerevisiae
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Crystal structures of ligand-bound saccharopine dehydrogenase from Saccharomyces cerevisiae
Biochemistry
46
12512-12521
2007
Saccharomyces cerevisiae (P38998)
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Xu, H.; West, A.H.; Cook, P.F.
Determinants of substrate specificity for saccharopine dehydrogenase from Saccharomyces cerevisiae
Biochemistry
46
7625-7636
2007
Saccharomyces cerevisiae
brenda
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Structural studies of the final enzyme in the alpha-aminoadipate pathway-saccharopine dehydrogenase from Saccharomyces cerevisiae
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373
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2007
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Glutamates 78 and 122 in the active site of saccharopine dehydrogenase contribute to reactant binding and modulate the basicity of the acid-base catalysts
J. Biol. Chem.
285
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2010
Saccharomyces cerevisiae
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The oxidation state of active site thiols determines activity of saccharopine dehydrogenase at low pH
Arch. Biochem. Biophys.
513
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2011
Saccharomyces cerevisiae
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Supporting role of lysine 13 and glutamate 16 in the acid-base mechanism of saccharopine dehydrogenase from Saccharomyces cerevisiae
Arch. Biochem. Biophys.
522
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2012
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Evidence in support of lysine 77 and histidine 96 as acid-base catalytic residues in saccharopine dehydrogenase from Saccharomyces cerevisiae
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51
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2012
Saccharomyces cerevisiae (P38998)
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Theoretical study on the proton shuttle mechanism of saccharopine dehydrogenase
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44
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2013
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Two NAD-linked redox shuttles maintain the peroxisomal redox balance in Saccharomyces cerevisiae
Sci. Rep.
7
11868
2017
Saccharomyces cerevisiae (P38998), Saccharomyces cerevisiae ATCC 204508 (P38998)
brenda