Disease relevance of alpha-Oxobenzeneacetic acid

• (S)-Mandelate dehydrogenase (MDH) from Pseudomonas putida is a flavin mononucleotide (FMN)-dependent enzyme that oxidizes (S)-mandelate to benzoylformate [1].
• The gene for benzoylformate decarboxylase has been expressed in Escherichia coli with the trc promoter, and homogeneous enzyme has been isolated from induced cells [2].
• The solvent kinetic isotope effects are compared to those on two related enzymes not subject to substrate activation, Zymomonas mobilis pyruvate decarboxylase and benzoylformate decarboxylase [3].
• Phenylacetyl-CoA:acceptor oxidoreductase, a new alpha-oxidizing enzyme that produces phenylglyoxylate. Assay, membrane localization, and differential production in Thauera aromatica [4].
• The phenylglyoxylate oxidizing enzyme activity in the denitrifying bacterium Azoarcus evansii was induced during anaerobic growth with phenylalanine, phenylacetate and phenylglyoxylate, but not with benzoate [5].

High impact information on alpha-Oxobenzeneacetic acid

• This suggests that an enzyme that generates an aldehyde from a 2-ketoacid should have functional Br??nsted acids in their active sites that would trap the carbanion, as does benzoylformate decarboxylase [6].
• The metabolism of styrene to styrene oxide and further conversion to styrene glycol (via epoxide hydrolase), mandelic acid, and phenylglyoxylic acid has been given considerable attention, and is considered to be the major pathway of activation and detoxication for humans [7].
• Studies with para-substituted benzoylformate substrates demonstrate that the electronic properties of the substrate affect the stabilization or destabilization of the carbanion intermediate or carbanion-like transition state and in that way alter the rate dependence on decarboxylation [8].
• The steady-state distribution of covalent ThDP intermediates of IPDC reacting with 3-indolepyruvate and the alternative substrates benzoylformate and pyruvate has been analyzed by (1)H NMR spectroscopy [8].
• The enzyme is part of a superfamily of ThDP-dependent 2-oxo acid decarboxylases that includes pyruvate decarboxylase, benzoylformate decarboxylase, and acetohydroxy acid synthase, among others [9].

Chemical compound and disease context of alpha-Oxobenzeneacetic acid

• Benzoylformate decarboxylase (benzoylformate carboxy-lyase, BFD; EC 4.1.1.7) from Pseudomonas putida is a thiamine pyrophosphate (TPP) dependent enzyme which converts benzoylformate to benzaldehyde and carbon dioxide [10].
• Mandelate pathway of Pseudomonas putida: sequence relationships involving mandelate racemase, (S)-mandelate dehydrogenase, and benzoylformate decarboxylase and expression of benzoylformate decarboxylase in Escherichia coli [2].
• Pseudomonas putida is attracted to at least two groups of aromatic acids: a benzoate group and a benzoylformate group [11].
• Acyloin formation by benzoylformate decarboxylase from Pseudomonas putida [12].
• Benzaldehyde lyase from Pseudomonas fluorescens and benzoylformate decarboxylase from Pseudomonas putida are homologous thiamin diphosphate-dependent enzymes that catalyze carboligase and carbolyase reactions [13].

Biological context of alpha-Oxobenzeneacetic acid

• Carboligation constitutes a side reaction of BFD, whereas the predominant physiological task of the enzyme is the non-oxidative decarboxylation of benzoylformate [14].
• The kinetics and mechanism of the benzoylformate decarboxylase reaction were studied by solvent deuterium and 13C kinetic isotope effects with benzoylformate and a series of substituted benzoylformates (pCH3O, pCH3, pCl, and mF) [10].
• Benzoylformate did not stimulate protein methylation in cells induced for benzoylformate chemotaxis, suggesting that sensory input from this second group of aromatic-acid attractants is processed through a different kind of chemosensory pathway [11].
• Alteration of the substrate specificity of benzoylformate decarboxylase from Pseudomonas putida by directed evolution [15].
• The major urinary metabolites derived from the biotransformation of SO in man are mandelic acid (MA) and phenylglyoxylic acid (PGA) [16].

Anatomical context of alpha-Oxobenzeneacetic acid

• Quantification of 2-ketoglutaric acid in plasma and cerebrospinal fluid as its O-trimethylsilyl++-quinoxalinol derivative by gas chromatography chemical ionization mass spectrometry is described with benzoylformic acid as internal standard [17].

Associations of alpha-Oxobenzeneacetic acid with other chemical compounds

• A structure of this enzyme binding (R)-mandelate, a competitive inhibitor, suggests that at least two hydrogen bonds are formed between the substrate, benzoylformate, and active site side chains [18].
• The l-mandelate dehydrogenase (L-MDH) from the yeast Rhodotorula graminis is a mitochondrial flavocytochrome b2 which catalyses the oxidation of mandelate to phenylglyoxylate coupled with the reduction of cytochrome c. We have used the N-terminal sequence of the enzyme to isolate the gene encoding this enzyme using the PCR [19].
• The chemotactic responses of P. putida cells to benzoate and benzoylformate were not sensitive to external pH over a range (6.2 to 7.7) which would vary the protonated forms of these weak acids by a factor of about 30 [11].
• Large, single crystals of benzoylformate decarboxylase were grown from solutions of buffered polyethylene glycol 400, pH 8 [20].
• The substrates 2-oxocaproate, 2-oxoisocaproate, phenylpyruvate, phenylglyoxylate, keto-tert-leucine and pyruvate were fitted into the active site of the subsequently refined model [21].

Gene context of alpha-Oxobenzeneacetic acid

• Each day, the following urinary metabolites were analysed from samples collected during exposure (0-6 h) and after exposure (6-24 h): mandelic acid; phenylglyoxylic acid; and two mercapturic acids, N-acetyl-S-(1-phenyl-2-hydroxyethyl)-L-cysteine (M1) and N-acetyl-S-(2-phenyl-2-hydroxyethyl)-L-cysteine (M2) [22].
• Examination of growth curves and patterns of substrate utilization, as well as measurement of enzyme activities, showed that benzyl alcohol dehydrogenase and benzaldehyde dehydrogenase II are repressed when A. calcoaceticus utilizes L-mandelate or phenylglyoxylate [23].

Analytical, diagnostic and therapeutic context of alpha-Oxobenzeneacetic acid

• Purification and crystallization of benzoylformate decarboxylase [20].
• Improving the carboligase activity of benzoylformate decarboxylase from Pseudomonas putida by a combination of directed evolution and site-directed mutagenesis [24].
• Enantioseparation by HPLC using phenylcarbonate, benzoylformate, p-toluenesulfonylcarbamate, and benzoylcarbamates of cellulose and amylose as chiral stationary phases [25].
• Acetone and styrene concentrations in whole blood, serum and urine were measured by head-space gas chromatography, and phenylglyoxylic acid in urine by high-performance liquid chromatography [26].
• Construction of an electro-enzymatic bioreactor for the production of (R)-mandelate from benzoylformate [27].

References