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Literature summary for 2.6.1.7 extracted from

  • Han, Q.; Cai, T.; Tagle, D.A.; Li, J.
    Structure, expression, and function of kynurenine aminotransferases in human and rodent brains (2010), Cell. Mol. Life Sci., 67, 353-368.
    View publication on PubMedView publication on EuropePMC

Inhibitors

Inhibitors Comment Organism Structure
(S)-4-ethylsulfonylbenzoylalanine specific inhibitor of KAT II Rattus norvegicus
3-hydroxykynurenine 5 mM decreases KAT II activity Homo sapiens
3-indolepropionic acid specific inhibition of KAT I activity Homo sapiens
aminoadipate 5 mM decreases KAT II activity Homo sapiens
DL-indole-3-lactic acid specific inhibition of KAT I activity Homo sapiens
L- glutamate 5 mM decreases KAT II activity Homo sapiens
L-asparagine 5 mM decreases KAT II activity Homo sapiens
L-aspartate specific inhibitor of KAT IV Homo sapiens
L-cysteine 5 mM decreases KAT II activity; inhibition of human KAT I activity at 2 mM Homo sapiens
L-glutamine inhibition of KAT I activity at 2 mM Homo sapiens
L-histidine 5 mM decreases KAT II activity Homo sapiens
L-lysine 5 mM decreases KAT II activity Homo sapiens
L-methionine specific inhibitor of KAT III Mus musculus
L-phenylalanine 5 mM decreases KAT II activity; inhibition of KAT I activity at 2 mM Homo sapiens
L-tryptophan specific inhibition of KAT I activity at 2 mM Homo sapiens
L-tryptophan KAT I is greatly and specifically inhibited by 5 mM L-tryptophan Mus musculus
methionine KAT III is greatly inhibited by 5 mM methionine Mus musculus
additional information KAT I is not inhibited by 2 mM methionine Homo sapiens
additional information KAT III is not inhibited by 5 mM tryptophan; KAT I is not inhibited by 5 mM L-methionine Mus musculus
Tris amine the commonly used buffer for KAT I assays greatly inhibits KAT I around neutral pH conditions, but shows no inhibition at basic pH condition Homo sapiens
tryptophan KAT I is greatly inhibited by 2 mM tryptophan Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
mitochondrion KAT IV Mus musculus 5739
-
mitochondrion KAT IV Homo sapiens 5739
-
mitochondrion KAT IV Rattus norvegicus 5739
-

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-
Mus musculus
-
-
-
Rattus norvegicus
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
brain
-
Mus musculus
-
brain
-
Homo sapiens
-
brain
-
Rattus norvegicus
-
heart
-
Homo sapiens
-
liver
-
Mus musculus
-
liver
-
Homo sapiens
-
liver
-
Rattus norvegicus
-
placenta
-
Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
L-kynurenine + 2-oxoglutarate
-
Mus musculus kynurenic acid + L-glutamate + H2O
-
?
L-kynurenine + 2-oxoglutarate
-
Homo sapiens kynurenic acid + L-glutamate + H2O
-
?
L-kynurenine + 2-oxoglutarate
-
Rattus norvegicus kynurenic acid + L-glutamate + H2O
-
?
additional information KAT I is most active with large neutral/aromatic/sulfur-containing amino acids, including L-glutamine, L-phenylalanine, L-leucine, L-kynurenine, L-tryptophan, L-methionine, L-tyrosine, L-histidine, L-cysteine, aminobutyrate, S-(1,1,2,2-tetrafluoroethyl)-L-cysteine, and S-(1,2-dichlorovinyl)-L-cysteine. The enzyme has detectable activity with Se-methylselenocysteine, 5-S-cysteinyldopamine, 5-S-cysteinyl-DOPA, L-asparagine, glycine, L-alanine, L-arginine, L-serine, and L-lysine. KAT I can use many 2-oxo acids as its amino group acceptors: 2-oxoglutarate, 2-oxocaproic acid, phenylpyruvate, 2-oxo-4-methylthiobutyrate, mercaptopyruvate, indo-3-pyruvate, 2-oxovalerate, 2-oxoleucine, 2-oxobutyrate, p-hydroxyphenylpyruvate, 2-oxoadipate, glyoxylate, oxaloacetate, 2-oxovaline, 2-oxoisoleucine, and pyruvate. All of them demonstrate the capacity to act as amino group acceptors, but 2-oxoglutarate, 2-oxoiosleucine, indol-3-ylpyruvate, 2-oxoadipate, and 2-oxovaline have very low activity. Although the activity of KAT I using oxaloacetate, phenylpyruvate, or pyruvate as an amino group acceptor is detectable, the specific activity with these three 2-oxo acids is so low that they are unlikely to be physiological co-substrates for human KAT I Mus musculus ?
-
?
additional information KAT I is most active with large neutral/aromatic/sulfur-containing amino acids, including L-glutamine, L-phenylalanine, L-leucine, L-kynurenine, L-tryptophan, L-methionine, L-tyrosine, L-histidine, L-cysteine, aminobutyrate, S-(1,1,2,2-tetrafluoroethyl)-L-cysteine, and S-(1,2-dichlorovinyl)-L-cysteine. The enzyme has detectable activity with Se-methylselenocysteine, 5-S-cysteinyldopamine, 5-S-cysteinyl-DOPA, L-asparagine, glycine, L-alanine, L-arginine, L-serine, and L-lysine. KAT I can use many 2-oxo acids as its amino group acceptors: 2-oxoglutarate, 2-oxocaproic acid, phenylpyruvate, 2-oxo-4-methylthiobutyrate, mercaptopyruvate, indol-3-ylpyruvate, 2-oxovalerate, 2-oxoleucine, 2-oxobutyrate, p-hydroxyphenylpyruvate, 2-oxoadipate, glyoxylate, oxaloacetate, 2-oxovaline, 2-oxoisoleucine, and pyruvate. All of them demonstrate the capacity to act as amino group acceptors, but 2-oxoglutarate, 2-oxoiosleucine, indo-3-pyruvate, 2-oxoadipate, and 2-oxovaline have very low activity. Although the activity of KAT I using oxaloacetate, phenylpyruvate, or pyruvate as an amino group acceptor is detectable, the specific activity with these three 2-oxo acids is so low that they are unlikely to be physiological co-substrates for human KAT I Homo sapiens ?
-
?
additional information KAT I is most active with large neutral/aromatic/sulfur-containing amino acids, including L-glutamine, L-phenylalanine, L-leucine, L-kynurenine, L-tryptophan, L-methionine, L-tyrosine, L-histidine, L-cysteine, aminobutyrate, S-(1,1,2,2-tetrafluoroethyl)-L-cysteine, and S-(1,2-dichlorovinyl)-L-cysteine. The enzyme has detectable activity with Se-methylselenocysteine, 5-S-cysteinyldopamine, 5-S-cysteinyl-DOPA, L-asparagine, glycine, L-alanine, L-arginine, L-serine, and L-lysine. KAT I can use many 2-oxo acids as its amino group acceptors: 2-oxoglutarate, 2-oxocaproic acid, phenylpyruvate, 2-oxo-4-methylthiobutyrate, mercaptopyruvate, indol-3-ylpyruvate, 2-oxovalerate, 2-oxoleucine, 2-oxobutyrate, p-hydroxyphenylpyruvate, 2-oxoadipate, glyoxylate, oxaloacetate, 2-oxovaline, 2-oxoisoleucine, and pyruvate. All of them demonstrate the capacity to act as amino group acceptors, but 2-oxoglutarate, 2-oxoisoleucine, indol-3-ylpyruvate, 2-oxoadipate, and 2-oxovaline have very low activity. Although the activity of KAT I using oxaloacetate, phenylpyruvate, or pyruvate as an amino group acceptor is detectable, the specific activity with these three 2-oxo acids is so low that they are unlikely to be physiological co-substrates for human KAT I Rattus norvegicus ?
-
?
additional information KAT II is efficient in catalyzing the transamination of aminoadipate, L-kynurenine, L-methionine, and L-glutamate, and is less efficient in catalyzing L-tyrosine, L-phenylalanine, L-tryptophan, L-leucine, 3-hydroxykynurenine, L-glutamine, L-alanine, and aminobutyrate. KAT II is efficient in catalyzing the transamination of 2-oxoglutarate, 2-oxocaproic acid, phenylpyruvate, and 2-oxo-4-methylthiobutyrate, and less efficient in catalyzing mercaptopyruvate, indol-3-ylpyruvate, 2-oxovalerate, 2-oxoleucine, 2-oxobutyrate, p-hydroxyphenylpyruvate, 2-oxoadipate, glyoxylate, oxaloacetate, 2-oxovaline, 2-oxoisoleucine, and pyruvate (in order of decreasing catalytic efficiency) Homo sapiens ?
-
?
additional information KAT II is efficient in catalyzing the transamination of aminoadipate, L-kynurenine, L-methionine, and L-glutamate, and is less efficient in catalyzing L-tyrosine, L-phenylalanine, L-tryptophan, L-leucine, 3-hydroxykynurenine, L-glutamine, L-alanine, and aminobutyrate. KAT II is efficient in catalyzing the transamination of 2-oxoglutarate, 2-oxocaproic acid, phenylpyruvate, and 2-oxo-4-methylthiobutyrate, and less efficient in catalyzing mercaptopyruvate, indol-3-ylpyruvate, 2-oxovalerate, 2-oxoleucine, 2-oxobutyrate, p-hydroxyphenylpyruvate, 2-oxoadipate, glyoxylate, oxaloacetate, 2-oxovaline, 2-oxoisoleucine, and pyruvate (in order of decreasing catalytic efficiency) Rattus norvegicus ?
-
?
additional information KAT II is efficient in catalyzing the transamination of aminoadipate, L-kynurenine, L-methionine, and L-glutamate, and is less efficient in catalyzing L-tyrosine, L-phenylalanine, L-tryptophan, L-leucine, 3-hydroxykynurenine, L-glutamine, L-alanine, and aminobutyrate. KAT II is efficient in catalyzing the transamination of 2-oxoglutarate, 2-oxocaproic acid, phenylpyruvate, and alpha-oxo-gamma-methiol-butyric acid, and less efficient in catalyzing mercaptopyruvate, indol-3-ylpyruvate, 2-oxovalerate, 2-oxoleucine, 2-oxobutyrate, p-hydroxyphenylpyruvate, 2-oxoadipate, glyoxylate, oxaloacetate, 2-oxovaline, 2-oxoisoleucine, and pyruvate (in order of decreasing catalytic efficiency) Mus musculus ?
-
?
additional information KAT III shows activity towards L-phenylalanine, L-kynurenine, L-tryptophan, 3-hydroxykynurenine, L-tyrosine, and L-histidine, L-methionine and L-cysteine, L-glutamine, L-asparagine, L-serine, L-alanine, aminobutyrate, and L-lysine. Glyoxylate, 2-oxocaproic acid, phenylpyruvate, 2-oxobutyrate, 2-oxo-4-methylthiobutyrate, 2-oxovalerate, indol-3-ylpyruvate, p-hydroxyphenylpyruvate, mercaptopyruvate, and oxaloacetate are good amino group acceptors for KAT III and pyruvate, phenylpyruvate, while 2-oxoglutarate are poor co-substrates for the enzyme Homo sapiens ?
-
?
additional information KAT III shows activity towards L-phenylalanine, L-kynurenine, L-tryptophan, 3-hydroxykynurenine, L-tyrosine, and L-histidine, L-methionine and L-cysteine, L-glutamine, L-asparagine, L-serine, L-alanine, aminobutyrate, and L-lysine. Glyoxylate, 2-oxocaproic acid, phenylpyruvate, 2-oxobutyrate, 2-oxo-4-methylthiobutyrate, 2-oxovalerate, indol-3-ylpyruvate, p-hydroxyphenylpyruvate, mercaptopyruvate, and oxaloacetate are good amino group acceptors for KAT III and pyruvate, phenylpyruvate, while 2-oxoglutarate are poor co-substrates for the enzyme Rattus norvegicus ?
-
?
additional information KAT III shows activity towards L-phenylalanine, L-kynurenine, L-tryptophan, 3-hydroxykynurenine, L-tyrosine, and L-histidine, L-methionine and L-cysteine, L-glutamine, L-asparagine, L-serine, L-alanine, aminobutyrate, and L-lysine. Glyoxylate, 2-oxocaproic acid, phenylpyruvate, 2-oxobutyrate, alpha-oxo-gamma-methiol-butyric acid, 2-oxovalerate, indo-3-pyruvate, p-hydroxyphenylpyruvate, mercaptopyruvate, and oxaloacetate are good amino group acceptors for KAT III and pyruvate, phenylpyruvate, while 2-oxoglutarate are poor co-substrates for the enzyme Mus musculus ?
-
?
additional information KAT IV shows high transamination activity towards L-glutamate, L-aspartate, L-phenylalanine, L-tyrosine, and L-cysteine, and detectable activity towards L-tryptophan, 3-hydroxykynurenine, L-methionine, L-kynurenine, and L-asparagine. It can use 2-oxoglutarate, phenylpyruvate, 2-oxo-4-methylthiobutyrate, indol-3-ylpyruvate, hydroxyphenylpyruvate, mercaptopyruvate, 2-oxocaproic acid, oxaloacetate, 2-oxobutyrate, pyruvate, and glyoxylate as amino group acceptors. It also shows detectable activity towards other co-substrates, including 2-oxovalerate, 2-oxoleucine, 2-oxoadipate, 2-oxovaline, and 2-oxoisoleucine Mus musculus ?
-
?
additional information KAT IV shows high transamination activity towards L-glutamate, L-aspartate, L-phenylalanine, L-tyrosine, and L-cysteine, and detectable activity towards L-tryptophan, 3-hydroxykynurenine, L-methionine, L-kynurenine, and L-asparagine. It can use 2-oxoglutarate, phenylpyruvate, 2-oxo-4-methylthiobutyrate, indol-3-ylpyruvate, hydroxyphenylpyruvate, mercaptopyruvate, 2-oxocaproic acid, oxaloacetate, 2-oxobutyrate, pyruvate, and glyoxylate as amino group acceptors. It also shows detectable activity towards other co-substrates, including 2-oxovalerate, 2-oxoleucine, 2-oxoadipate, 2-oxovaline, and 2-oxoisoleucine Homo sapiens ?
-
?
additional information KAT IV shows high transamination activity towards L-glutamate, L-aspartate, L-phenylalanine, L-tyrosine, and L-cysteine, and detectable activity towards L-tryptophan, 3-hydroxykynurenine, L-methionine, L-kynurenine, and L-asparagine. It can use 2-oxoglutarate, phenylpyruvate, 2-oxo-4-methylthiobutyrate, indol-3-ylpyruvate, hydroxyphenylpyruvate, mercaptopyruvate, 2-oxocaproic acid, oxaloacetate, 2-oxobutyrate, pyruvate, and glyoxylate as amino group acceptors. It also shows detectable activity towards other co-substrates, including 2-oxovalerate, 2-oxoleucine, 2-oxoadipate, 2-oxovaline, and 2-oxoisoleucine Rattus norvegicus ?
-
?

Synonyms

Synonyms Comment Organism
KAT I also called GTK or CCBL1 Mus musculus
KAT I also called GTK or CCBL1 Homo sapiens
KAT I also called GTK or CCBL1 Rattus norvegicus
KAT II also called AADAT Mus musculus
KAT II also called AADAT Homo sapiens
KAT II also called AADAT Rattus norvegicus
KAT III also called CCBL2 Mus musculus
KAT III also called CCBL2 Homo sapiens
KAT III also called CCBL2 Rattus norvegicus
KAT IV also called mitochondrial ASAT or GOT2 Mus musculus
KAT IV also called mitochondrial ASAT or GOT2 Homo sapiens
KAT IV also called mitochondrial ASAT or GOT2 Rattus norvegicus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
7
-
KAT II Homo sapiens
7 9 KAT IV Mus musculus
7.4 10 KAT I Homo sapiens
7.5
-
liver KAT I Rattus norvegicus
8
-
KAT IV Mus musculus
8 9 heart KAT I Homo sapiens
9 10 KAT III Mus musculus
9.5 10 optimal pH range of human brain and placenta KAT I Homo sapiens

Cofactor

Cofactor Comment Organism Structure
pyridoxal 5'-phosphate
-
Mus musculus
pyridoxal 5'-phosphate
-
Homo sapiens
pyridoxal 5'-phosphate
-
Rattus norvegicus