2-Carboxybenzaldehyde

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]

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

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-CBA is further metabolized to 2-hydroxymethylbenzoic acid by reduction of the aldehyde group. In the present work, the enzyme responsible for the reduction of 2-CBA in humans is identified as a homologue of rat aflatoxin B1-aldehyde reductase (rAFAR). This novel human aldo-keto reductase (AKR) has been cloned from a liver cDNA library, and together with the rat protein, establishes the AKR7 family of the AKR superfamily. Unlike its rat homologue, human AFAR (hAFAR) appears to be constitutively expressed in human liver, and is widely expressed in extrahepatic tissues. The deduced human and rat protein sequences share 78% identity and 87% similarity. Although the two AKR7 proteins are predicted to possess distinct secondary structural features which distinguish them from the prototypic AKR1 family of AKRs, the catalytic- and NADPH-binding residues appear to be conserved in both families. Certain of the predicted structural features of the AKR7 family members are shared with the AKR6 beta-subunits of voltage-gated K+-channels. 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-CBA, suggesting that hAFAR could function as both a SSA reductase and a 2-CBA reductase in vivo. This hypothesis is supported in part by the finding that the major peak of 2-CBA reductase activity in human liver co-purifies with hAFAR protein.

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

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

Effects of phenobarbital (PB) and L-methionine on 2-Carboxybenzaldehyde (CBA) reductase in rat hepatocyte primary culture were examined. 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.

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

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

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. All the compounds were non-electrolytic in nature. On the basis of spectral studies an octahedral geometry has been assigned for Ni(II) and a tetragonal geometry for Cu(II) complexes. The ligand and its metal complexes were screened for their anticancer studies against human breast cancer cell lines MCF-7 and calculated minimum inhibitory concentration and also for antibacterial activity using Kirby-Bauer single disk susceptibility test.

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

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

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. Experiments with cycloheximide suggest that de novo synthesis of the enzyme protein is enhanced by PB in primary culture.

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

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

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. 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. 6. The results suggest that sulphydryl substances and some proteins play important roles in preserving the molecular and catalytic properties of CBA reductase.