2-Carboxybenzaldehyde

Xenobiotica. 1992 Jun;22(6):691-9.

Purification and molecular properties of 2-carboxybenzaldehyde (CBA) reductase from phenobarbital-treated rat liver.[Pubmed: 1441592]

1. A rat liver cytosol enzyme, tentatively named CBA reductase, catalyses the conversion of 2-Carboxybenzaldehyde (CBA) to 2-hydroxymethyl benzoic acid in the presence of NADH (or NADPH). CBA reductase is useful for exploring the mechanism of in vitro enzyme induction, as the enzyme can be induced by phenobarbital (PB) both in vivo and in vitro.
METHODS AND RESULTS:
2. Possible involvement of glutathione (GSH) in gene expression was suggested by a recent study with cultured rat hepatocytes. 3. CBA reductase was purified about 200-fold by a combination of column chromatography and isoelectric focusing in the presence of mercaptoethanol. 4. The ability to form 2-hydroxymethyl benzoic acid was lost when the enzyme was chromatographed on a hydroxylapatite column in the absence of mercaptoethanol; however, it was restored if sulphydryl compounds or bovine serum albumin was added to the eluate from the column. 5. Gel filtration showed the molecular sizes of CBA reductase from the 105,000g supernatant fraction of rat liver extracts and the purified preparation were 64 kDa and 49 kDa, respectively.
CONCLUSIONS:
6. The results suggest that sulphydryl substances and some proteins play important roles in preserving the molecular and catalytic properties of CBA reductase.

Biochem Biophys Res Commun. 1986 Dec 15;141(2):488-93.

Induction of 2-carboxybenzaldehyde reductase by phenobarbital in primary culture of rat hepatocytes.[Pubmed: 3541933]

METHODS AND RESULTS:
When rats were treated with phenobarbital (PB), the activity of CBA reductase, which catalyzes the conversion of 2-Carboxybenzaldehyde (CBA) to 2-hydroxymethylbenzoic acid (HMB), in the liver was markedly enhanced. Likewise, addition of PB to the primary culture of rat hepatocytes increased the activity of CBA reductase. The enzyme recovered from cell lysate of cultured cells showed the same characteristics in molecular and catalytic properties as the enzyme purified from the livers of the rats treated with PB.
CONCLUSIONS:
Experiments with cycloheximide suggest that de novo synthesis of the enzyme protein is enhanced by PB in primary culture.

Chem Biol Interact. 1991;77(2):149-58.

Effect of L-methionine on 2-carboxybenzaldehyde reductase induction by phenobarbital in primary cultures of rat hepatocytes.[Pubmed: 1991334]

Effects of phenobarbital (PB) and L-methionine on 2-Carboxybenzaldehyde (CBA) reductase in rat hepatocyte primary culture were examined.
METHODS AND RESULTS:
Inclusion of PB in the culture medium markedly enhanced the CBA reductase activity while L-methionine, which elevates the cellular glutathione (GSH) level, suppressed the stimulatory effect of PB. This suppression, though less pronounced, was also found with other precursors of GSH biosynthesis. GSH-depletors, buthionine sulfoximine (BSO) or diethylmaleate (DEM), enhanced the CBA reductase activity suggesting that GSH plays an important role in enzyme induction.

Spectrochim Acta A Mol Biomol Spectrosc. 2014 Aug 14;129:333-8.

Synthesis, spectroscopic, anticancer and antibacterial studies of Ni(II) and Cu(II) complexes with 2-carboxybenzaldehyde thiosemicarbazone.[Pubmed: 24747857]

Ni(II) and Cu(II) complexes of 2-Carboxybenzaldehyde thiosemicarbazone (L) were synthesized and investigated by their spectral and analytical data. These newly synthesized complexes have a composition of M(L)X(H2O)2 (where M=Ni(II), Cu(II) and X=Cl(-), NO3(-), CH3COO(-)) and (L) is the tridentate Schiff base ligand. The ligand and its complexes have been characterized on the basis of analytical, molar conductivity, magnetic susceptibility measurements, FT-IR, ESR, (1)H NMR and electronic spectral analysis.

Biochem J. 1998 May 15;332 ( Pt 1):21-34.

Molecular cloning, expression and catalytic activity of a human AKR7 member of the aldo-keto reductase superfamily: evidence that the major 2-carboxybenzaldehyde reductase from human liver is a homologue of rat aflatoxin B1-aldehyde reductase.[Pubmed: 9576847]

The masking of charged amino or carboxy groups by N-phthalidylation and O-phthalidylation has been used to improve the absorption of many drugs, including ampicillin and 5-fluorouracil. Following absorption of such prodrugs, the phthalidyl group is hydrolysed to release 2-Carboxybenzaldehyde (2-CBA) and the pharmaceutically active compound; in humans, 2-Carboxybenzaldehyde is further metabolized to 2-hydroxymethylbenzoic acid by reduction of the aldehyde group.
METHODS AND RESULTS:
In the present work, the enzyme responsible for the reduction of 2-Carboxybenzaldehyde in humans is identified as a homologue of rat aflatoxin B1-aldehyde reductase (rAFAR).In addition to reducing the dialdehydic form of aflatoxin B1-8,9-dihydrodiol, hAFAR shows high affinity for the gamma-aminobutyric acid metabolite succinic semialdehyde (SSA) which is structurally related to 2-Carboxybenzaldehyde, suggesting that hAFAR could function as both a SSA reductase and a 2-Carboxybenzaldehyde reductase in vivo.
CONCLUSIONS:
This hypothesis is supported in part by the finding that the major peak of 2-Carboxybenzaldehyde reductase activity in human liver co-purifies with hAFAR protein.