Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Hydroxybenzoates”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 289 records · Page 16Linked to original sources
PubMed1985

Identification of urinary 3-ethoxy-4-hydroxybenzoic and 3-ethoxy-4-hydroxymandelic acids after dietary intake of ethyl vanillin.

It has been discovered recently that several patients undergoing urinary organic acid profiling excrete high concentrations of 3-ethoxy-4-hydroxybenzoic acid and traces of 3-ethoxy-4-hydroxymandelic acid. These are believed to be the consequences of feeding the patients with synthetic diets flavoured with 3-ethoxy-4-hydroxybenzaldehyde, a vanilla-like artificial flavouring added to improve patient acceptance and taste. The syntheses, mass spectra and gas chromatographic behaviour of these and related compounds are presented.

Adult↗
PubMed1994

Crystal structures of wild-type p-hydroxybenzoate hydroxylase complexed with 4-aminobenzoate,2,4-dihydroxybenzoate, and 2-hydroxy-4-aminobenzoate and of the Tyr222Ala mutant complexed with 2-hydroxy-4-aminobenzoate. Evidence for a proton channel and a new binding mode of the flavin ring.

The crystal structures of wild-type p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens, complexed with the substrate analogues 4-aminobenzoate, 2,4-dihydroxybenzoate, and 2-hydroxy-4-aminobenzoate have been determined at 2.3-, 2.5-, and 2.8-A resolution, respectively. In addition, the crystal structure of a Tyr222Ala mutant, complexed with 2-hydroxy-4-aminobenzoate, has been determined at 2.7-A resolution. The structures have been refined to R factors between 14.5% and 15.8% for data between 8.0 A and the high-resolution limit. The differences between these complexes and the wild-type enzyme-substrate complex are all concentrated in the active site region. Binding of substrate analogues bearing a 4-amino group (4-aminobenzoate and 2-hydroxy-4-aminobenzoate) leads to binding of a water molecule next to the active site Tyr385. As a result, a continuous hydrogen-bonding network is present between the 4-amino group of the substrate analogue and the side chain of His72. It is likely that this hydrogen-bonding network is transiently present during normal catalysis, where it may or may not function as a proton channel assisting the deprotonation of the 4-hydroxyl group of the normal substrate upon binding to the active site. Binding of substrate analogues bearing a hydroxyl group at the 2-position (2,4-dihydroxybenzoate and 2-hydroxy-4-aminobenzoate) leads to displacement of the flavin ring from the active site. The flavin is no longer in the active site (the "in" conformation) but is in the cleft leading to the active site instead (the "out" conformation). It is proposed that movement of the FAD out of the active site may provide an entrance for the substrate to enter the active site and an exit for the product to leave.

4-Aminobenzoic Acid↗
PubMed1991

Absorption spectra of radical forms of 2,4-dihydroxybenzoic acid, a substrate for p-hydroxybenzoate hydroxylase.

Combined optical and conductimetric measurements in aqueous solution indicate that at high pH (greater than or equal to 10).OH radicals react with the phenoxide form of 2,4-dihydroxybenzoic acid to form transiently phenoxyl radicals and a small amount of hydroxyeyclohexadienyl (HCHD) radicals by 150 ns. The respective yields of 88 and 12% of the total.OH radical yield were deduced from conductance and optical changes as well as from studies using a low potential reductant. The HCHD radical possesses a pKa of 8.0 +/- 0.1 and the constructed spectrum of the deprotonated forms of HCHD has a lambda max at 420 nm with a minimum extinction coefficient of approximately 7250 M-1 cm-1. The red shift in lambda max and increase in extinction coefficient compared to the revised spectral properties of the protonated form of the HCHD radical (lambda max at 390 nm with extinction coefficient of approximately 4500 M-1 cm-1), together with the pKa of the HCHD radical, provide an explanation for the pH-dependent spectral changes of the so-called highly absorbing intermediate II species, observed in the functioning of the enzyme p-hydroxybenzoate hydroxylase. These results add further to the evidence in support of the proposal that intermediate II is composed of species which absorb similarly to the flavin 4(a)-hydroxide and a form of the substrate/product such as the HCHD radical (Anderson, R. F., Patel, K. B., and Stratford, M. R. L. (1987) J. Biol. Chem. 262, 17475-17479).

4-Hydroxybenzoate-3-Monooxygenase↗
PubMed2004

Evaluation of a fibre optic device in solution equilibria studies. Application to 3-hydroxybenzoic acid ionization.

The use of a fibre optic device for spectrophotometric measurements in solution equilibria studies is presented. In particular the precision obtainable with such equipment is evaluated as a function of different experimental conditions, such as path length, averaging time and stirring of the solution. Analysis of 3-hydroxybenzoic acid ionization is presented to assess the results obtained in the study of an equilibrium system.

Fiber Optic Technology↗
PubMed1979

Enhanced chartreusin solubility by hydroxybenzoate hydrotropy.

The apparent aqueous solubility of the water-insoluble cytotoxic agent, chartreusin, was increased at neutral pH in the presence of hydroxybenzoates. Water molecules play an important role in the chartreusin conformation. Studies included solubility and spectral examinations. The weakest and strongest interactants with chartreusin were sodium benzoate and sodium trihydroxybenzoate, respectively, while the effect of mono- and dihydroxybenzoates was intermediate. A plane-to-plane orientation of chartreusin and the ligand molecules brought together by electrostatic and hydrophobic interactions is postulated. The dramatic chartreusin aqueous solubility increase relative to its aglycone, chartarin, under similar conditions was best rationalized by micellization.

Antibiotics, Antineoplastic↗
PubMed1992

Chloride-37 nuclear magnetic resonance spectroscopic study of binding of salicylic acid and other hydroxybenzoic acids to the band 3 anion transport protein of human erythrocytes.

Chloride-37 nuclear magnetic resonance spectroscopy was used to investigate the displacement of chloride (Cl-) from binding sites on band 3 anion transport protein in human erythrocytes by salicylic acid and five other hydroxybenzoic acids (HAs). All the HAs studied displaced Cl- from these binding sites. The association constants for binding of the HAs to band 3 anion transport protein were larger than that for Cl- and dependent on the specific structural features of the molecule, rather than general physicochemical characteristics.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1992

A kinetic study of the role of band 3 anion transport protein in the transport of salicylic acid and other hydroxybenzoic acids across the human erythrocyte membrane.

The mechanism of transport of salicylic acid and five other hydroxybenzoic acids across the human erythrocyte membrane was investigated. The specific anion transport inhibitor, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, reduced but did not totally abolish transport of these acids. This observation suggests that these acids are transported by two parallel processes, one involving the band 3 anion transport protein channel and the other probably involving passive diffusion of the un-ionized molecule. The activation energies for membrane transport were large (99-127 kJ.mol-1), an observation that is consistent with the rate-limiting step for anion transport being the conformational change of the band 3 anion transport protein.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1995

Model assembly study of the ligand binding by p-hydroxybenzoate hydroxylase: correlation between the calculated binding energies and the experimental dissociation constants.

The energies of binding of seven ligands by p-hydroxybenzoate hydroxylase (PHBH) were calculated theoretically. Direct enzyme-ligand interaction energies were calculated using the ab initio quantum mechanical model assembly of the active site at the 3-21G level. Solvation energies of the ligands needed in the evaluation of the binding energies were calculated with the semiempirical AM1-SM2 method and the long-range electrostatic interaction energies between the ligands and the protein matrix classically using the static charge distributions of the ligands and the protein. Energies for proton-transfer between the ligands' OH or SH substituent at position 4 and the active-site tyrosine within the ab initio model assemblies were calculated and compared to the corresponding pKas in aqueous solution. Excluding 3,4-dihydroxybenzoate, the natural product of PHBH, a linear relationship between the calculated binding energies and the experimental binding free energies was found with a correlation coefficient of 0.90. Contributions of the direct enzyme-ligand interaction energies, solvation energies and the long-range electrostatic interaction energies to the calculated binding energies were analyzed. The proton-transfer energies of the ligands with substituents ortho to the ionized OH were found to be perturbed less in the model calculations than the energies of their meta isomers as deduced from the corresponding pKas.

4-Hydroxybenzoate-3-Monooxygenase↗
PubMed1999

Switch of coenzyme specificity of p-hydroxybenzoate hydroxylase.

p-Hydroxybenzoate hydroxylase (PHBH) is the archetype of the family of NAD(P)H-dependent flavoprotein aromatic hydroxylases. These enzymes share a conserved FAD-binding domain but lack a recognizable fold for binding the pyridine nucleotide. We have switched the coenzyme specificity of strictly NADPH-dependent PHBH from Pseudomonas fluorescens by site-directed mutagenesis. To that end, we altered the solvent exposed helix H2 region (residues 33-40) of the FAD-binding domain. Non-conservative selective replacements of Arg33 and Tyr38 weakened the binding of NADPH without disturbing the protein architecture. Introduction of a basic residue at position 34 increased the NADPH binding strength. Double (M2) and quadruple (M4) substitutions in the N-terminal part of helix H2 did not change the coenzyme specificity. By extending the replacements towards residues 38 and 40, M5 and M6 mutants were generated which were catalytically more efficient with NADH than with NADPH. It is concluded that specificity in P. fluorescens PHBH is conferred by interactions of Arg33, Tyr38 and Arg42 with the 2'-phosphate moiety of bound NADPH, and that introduction of an acidic group at position 38 potentially enables the recognition of the 2'-hydroxy group of NADH. This is the first report on the coenzyme reversion of a flavoprotein aromatic hydroxylase.

4-Hydroxybenzoate-3-Monooxygenase↗
PubMed1975

[On the phenolic acids of vegetables. II. Hydroxycinnamic acids and hydroxybenzoic acids of fruit and seed vegetables (author's transl)].

Fruits of solanaceae (tomatoes, eggplant, and sweet peppers) almost exclusively contain hydroxycinnamic acid derivatives with caffeic acid dominating. Fruits of cucurbitaceae (cucumbers, melons, pumpkins, and zucchini) are extraordinary, because they show very low concentrations of phenolic acids (up to 10 mg/kg) accumulated in the peels. Peas and broad beans have relatively small contents of phenolic acids too. Their husks show like beans considerable concentrations of hydroxycinnamic acid derivatives with dominating p-coumaric acid. In the group of hydroxybenzoic acids derivatives of salicylic, gentisic and vanillic acid could be determined frequently, but mostly as traces.

Caffeic Acids↗
PubMed1996

Combinatorial synthesis of small-molecule libraries using 3-amino-5-hydroxybenzoic acid.

A non-peptide library of 2001 compounds has been prepared utilizing solid-phase techniques. The split/combine method was demonstrated to work well to form mixtures of compounds based on 3-amino-5-hydroxybenzoic acid as a core structure. The benzoic acid of the core structure served as the attachment point for the resin and the amino and hydroxy positions were variably substituted.

Aminobenzoates↗
PubMed1990

Engineering of microheterogeneity-resistant p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens.

By site-directed mutagenesis, Cys-116 was converted to Ser-116 in p-hydroxybenzoate hydroxylase (EC 1.14.13.2) from Pseudomonas fluorescens. In contrast to wild-type enzyme, the C116S mutant is no longer susceptible to oxidation by hydrogen peroxide and shows no reactivity towards 5,5'-dithiobis(2-nitrobenzoate). Crystals of the C116S mutant are isomorphous with the crystal form of wild-type enzyme. A difference electron density confirms the mutation made.

4-Hydroxybenzoate-3-Monooxygenase↗
PubMed1977

Studies of the metabolic fate of p-hydroxybenzoic acid in male and female cats.

Metabolic studies conducted on p-hydroxybenzoic acid orally administered at dose levels of 13 and 26 mg/kg to male and female cats have shown that the compound is rapidly excreted in the urine exclusively in the form of the glycine conjugate p-hydroxyhippuric acid. Similar results were obtained following either single administration or 7-day treatment. The metabolite in the urine was characterised by thin-layer chromatography, amino acid analysis and mass spectrometry.

Amino Acids↗
PubMed1993

Evolutionary divergence of pobA, the structural gene encoding p-hydroxybenzoate hydroxylase in an Acinetobacter calcoaceticus strain well-suited for genetic analysis.

The pobA gene encoding p-hydroxybenzoate hydroxylase (PobA) from Acinetobacter calcoaceticus has been developed as a genetic tool for the analysis of structure-function relationships in this enzyme. By exploiting the favorable genetic system of A. calcoaceticus strain ADP1, it is possible both to select and to map mutations which disturb PobA activity; characterization and sequence determination of mutants derived in this manner may complement site-directed studies with the homologous Pseudomonas aeruginosa gene. We have determined the nucleotide (nt) sequence of A. calcoaceticus pobA and performed a systematic comparison of the deduced amino acid (aa) sequence with that of the PobA enzyme from Pseudomonas fluorescens, for which the three-dimensional structure is known. Despite a 26% difference in the G+C content of the homologous genes, constraints against structural divergence of the proteins were revealed by an overall identity of 62.4% in the aligned aa sequences of PobA. Clusters of identical sequence occur at previously identified sites of ligand binding and at regions associated with subunit-subunit interaction. Based on the conservation of specific residues involved in flavin binding, we have assembled a consensus sequence for nicotinamide-flavoprotein monooxygenases which differs from that of the oxidoreductase class of flavoproteins. In addition to the conserved regions shared by the two PobA homologs, there are isolated pockets of divergence. The nt sequence divergence in one such region within the A. calcoaceticus gene can be attributed to the acquisition of short nt sequence repetitions.

4-Hydroxybenzoate-3-Monooxygenase↗
PubMed2006

Polymorphism and thermodynamics of m-hydroxybenzoic acid.

Solution and solid-state properties of m-hydroxybenzoic acid have been investigated. Two polymorphs were found where the monoclinic modification exhibits a higher stability than the orthorhombic form. The solubility of the monoclinic polymorph was determined between 10 and 50 degrees C in methanol, acetonitrile, acetic acid, acetone, water and ethyl acetate. The solubility of the orthorhombic polymorph was determined between 10 and 50 degrees C in acetonitrile, acetic acid, acetone and ethyl acetate. A thermodynamic analysis revealed a marked correlation between the molar solubility and the van't Hoff enthalpy of solution at constant temperature. In addition, in each solvent increased temperature resulted in increased van't Hoff enthalpy of solution. It is shown that the solubility data can be used to estimate melting properties for both polymorphs. The solubility ratio of the two forms and the DSC thermogram of the orthorhombic form strongly suggest that the system is monotropic. However, according to the polymorph rules of Burger and Ramberger, the estimated higher melting enthalpy and lower melting temperature of the orthorhombic form points towards an enantiotropic system. Hence, this system appears to be an exception to the Burger and Ramberger melting enthalpy rule, and the probable reason for this is found in the difference in the heat capacity of the two solid forms.

Calorimetry, Differential Scanning↗
PubMed2026

Toxicological effects of propyl 4-hydroxybenzoate on gallstone pathogenesis: An integrated mendelian randomization, network toxicology, and experimental study.

BACKGROUND: Gallstone disease is a prevalent digestive disorder with substantial global socioeconomic burden. Propyl 4-hydroxybenzoate (PP), a widely used paraben preservative, exhibits potential metabolic and hepatic toxicity, yet its role in gallstone pathogenesis remains unclear. This study aimed to explore the causal association between PP exposure and gallstone formation and the underlying mechanism. METHODS: Two-sample Mendelian randomization (MR) was performed using genome-wide association study (GWAS) data. Network toxicology, molecular docking, and molecular dynamics simulation were applied to screen for core targets. In vivo experiments, transcriptome sequencing, Western blot (WB), and ELISA were conducted for mechanistic validation. RESULTS: MR confirmed a causal link between circulating PP levels and an elevated risk of gallstones (P&#x202f;<&#x202f;0.05), with AKT1 identified as the key target. In mice, PP aggravated gallstone formation by activating the AKT1-NF-&#x3ba;B-CXCL1 pathway, enhancing hepatic inflammation and neutrophil extracellular traps (NETs) formation; these effects were reversed by AKT inhibition. CONCLUSION: PP promotes gallstone formation via the AKT1-NF-&#x3ba;B-CXCL1-NETs axis. Our findings highlight PP as an environmental risk factor for gallstones, providing novel insights into their prevention and targeted therapy.

Animals↗