Reviewed: Jassal, B, 2010-11-09 Edited: D'Eustachio, P, 2010-07-01 Authored: D'Eustachio, P, 2010-07-01 CCBL1 (KAT 1) catalyzes the reaction of kynurenine and pyruvate to form 4-(2-aminophenyl)-2,4-dioxobutanoate and alanine. The active form of CCBL1 is a homodimer with one molecule of pyridoxal phosphate bound to each monomer (Baran et al. 1994; Han et al. 2009; Rossi et al. 2004). The enzyme's cytosolic localization is inferred from that of recombinant protein overexpressed in transfected cells (Perry et al. 1995). The pH optimum observed for CCBL1 in vitro is 9.5 - 10.0, so its role in kynurenine metabolism in vivo is not clear (Baran et al. 1994).<p>Biochemical studies of CCBL1 activity in vitro (e.g., Baren et al. 1994) invariably measure kynurenic acid as the reaction product, not 4-(2-aminophenyl)-2,4-dioxobutanoate, the product to be expected from transamination of kynurenine. The condensation of 4-(2-aminophenyl)-2,4-dioxobutanoate and elimination of a water molecule to form kynurenic acid has not been demonstrated directly. As noted by Miller et al. (1953), discussing their characterization of a bacterial form of the enzyme, "The keto acid assumed to be formed prior to ring closure in the conversion of kynurenine to kynurenic acid has not yet been detected. In principle, such detection should be possible, since it is sufficiently stable to have been synthesized. It also remains to be established whether ring closure is spontaneous, enzymatic, or both. The formation of kynurenic acid from L-kynurenine by the L-amino acid oxidase of Neurospora suggests, however, that ring closure can be spontaneous, unless the somewhat improbable assumption is made that Neurospora filtrate contained the ring-closing enzyme."

http://purl.obolibrary.org/obo/HINO_0024581

Reviewed: Jassal, B, 2010-11-09

Edited: D'Eustachio, P, 2010-07-01

Authored: D'Eustachio, P, 2010-07-01

CCBL1 (KAT 1) catalyzes the reaction of kynurenine and pyruvate to form 4-(2-aminophenyl)-2,4-dioxobutanoate and alanine. The active form of CCBL1 is a homodimer with one molecule of pyridoxal phosphate bound to each monomer (Baran et al. 1994; Han et al. 2009; Rossi et al. 2004). The enzyme's cytosolic localization is inferred from that of recombinant protein overexpressed in transfected cells (Perry et al. 1995). The pH optimum observed for CCBL1 in vitro is 9.5 - 10.0, so its role in kynurenine metabolism in vivo is not clear (Baran et al. 1994).

Biochemical studies of CCBL1 activity in vitro (e.g., Baren et al. 1994) invariably measure kynurenic acid as the reaction product, not 4-(2-aminophenyl)-2,4-dioxobutanoate, the product to be expected from transamination of kynurenine. The condensation of 4-(2-aminophenyl)-2,4-dioxobutanoate and elimination of a water molecule to form kynurenic acid has not been demonstrated directly. As noted by Miller et al. (1953), discussing their characterization of a bacterial form of the enzyme, "The keto acid assumed to be formed prior to ring closure in the conversion of kynurenine to kynurenic acid has not yet been detected. In principle, such detection should be possible, since it is sufficiently stable to have been synthesized. It also remains to be established whether ring closure is spontaneous, enzymatic, or both. The formation of kynurenic acid from L-kynurenine by the L-amino acid oxidase of Neurospora suggests, however, that ring closure can be spontaneous, unless the somewhat improbable assumption is made that Neurospora filtrate contained the ring-closing enzyme."

Pubmed19338303

Pubmed7883047

Pubmed15364907

Reactome, http://www.reactome.org

Pubmed13069505

Pubmed8294935

http://purl.obolibrary.org/obo/CHEBI_16946

http://purl.obolibrary.org/obo/CHEBI_32816

http://purl.obolibrary.org/obo/CHEBI_16977

http://purl.obolibrary.org/obo/CHEBI_17442

kynurenine + pyruvate => 4-(2-aminophenyl)-2,4-dioxobutanoic acid + alanine [CCBL1]

HINO:0024581

kynurenine + pyruvate => 4-(2-aminophenyl)-2,4-dioxobutanoic acid + alanine [CCBL1]

ReactomeREACT_25349

Reactome Database ID Release 43893596

EC Number: 2.6.1.7

http://purl.obolibrary.org/obo/INO_0000040