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PubMed1997

A novel device for capturing breath samples for solvent analysis.

We have developed a novel breath sampling device suitable for capturing a portion of end-tidal air. This breath sample is then transferred onto a Perkin Elmer automated thermal desorption (ATD) sampling tube which is subsequently analysed by ATD-gas chromatography-mass spectrometry (GCMS). The breath sampler has been evaluated in the laboratory, in brief field trials and in human volunteer studies. The method is sensitive with a typical detection limit of 1 nmol/l and reproducible with an overall coefficient of variation between 5% and 15% for collection and analysis of breath samples from volunteers. The field trials used the sampler to assess exposure to solvents in several industries including the shoe manufacturing industry, the inks and coatings industry and at dry cleaning establishments. The sampler was found easy to use and reliable. Solvents detected include ethyl acetate (6.4-25.5 nmol/l), propan-2-ol (3.4-39.3 nmol/l), 2-butanone (0-6.6 nmol/l) and tetrachloroethene (0-557 nmol/l). The breath sampler was also used to monitor the elimination of solvents in breath from human volunteers after exposure chamber studies. More than 500 breath samples have been analysed from 24 volunteers in exposures to 10 different solvents (toluene, trimethyl benzene, tetrachloroethene, tetrahydrofuran, acetone, propan-2-ol, xylene, 2-butanone, 1-methoxy-2-propanol and n-hexane). The breath sampler allowed the rapid and non-invasive collection of data on elimination of solvents.

Absorption↗
PubMed2002

Low viscosity dimethacrylate comonomer compositions [Bis-GMA and CH3Bis-GMA] for novel dental composites; analysis of the network by stray-field MRI, solid-state NMR and DSC & FTIR.

The effect of dilution of 2,2-bis (4-(2-hydroxy-3-methacryloxyprop-1-oxy) phenyl) propane (Bis-GMA) with 2,2-bis(4-(2-methacryloxyprop-1-oxy)phenyl) propane (CH3Bis-GMA) on extent of polymerization (Ep) was investigated by FTIR and NMR. The results correlate well with Ep values of the system and its flexibility probed by Tg (obtained by DSC). Spatially resolved photopolymerization kinetics and polymerization shrinkage (PS, i.e. volumetric polymerization contraction) was also studied by stray-field imaging (STRAFI-MRI). PS was obtained in the presence of oxygen from the atmosphere as the total volumetric contraction. All the results were compared with those obtained for the Bis-GMA/TEGDMA (triethylene glycol dimethacrylate) system. Use of Bis-GMA mixed with hydrophobic low viscosity CH3Bis-GMA comonomer, as a substitute for the commonly used TEGDMA, resulted in improving significantly properties such as PS, water sorption and Ep, thereby reducing the unreacted double bond concentration.

Acrylates↗
PubMed2000

Degradation of nonphenolic lignin by the laccase/1-hydroxybenzotriazole system.

Phenolic and nonphenolic (permethylated) synthetic [14C]lignins were depolymerized by Trametes villosa laccase in the presence of a radical mediator, 1-hydroxybenzotriazole (HOBT). Gel permeation chromatography of the treated lignins showed that approximately 10% of their substructures were cleaved. The system also cleaved a beta-O-4-linked model compound, 1-(4-ethoxy-3-methoxy-ring-[14C]phenyl)-2-(2-methoxyphenoxy)-propane- 1,3-diol, and a beta-1-linked model, 1, 2-bis-(3-methoxy-4-[14C]methoxyphenyl)-propane-1,3-diol, that represent nonphenolic substructures in lignin. High performance liquid chromatography of products from the oxidized models showed that they were produced in sufficient yields to account for the ability of laccase/HOBT to depolymerize nonphenolic lignin.

Dimerization↗
PubMed1985

Highly selective extraction of spiralin from the Spiroplasma citri cell membrane with alkyl-N-sulfobetaines.

The extraction of proteins from the membrane of the mollicute (mycoplasma) Spiroplasma citri by sodium N-dodecyl-N,N-dimethyl-3-amino-1-propane sulfonate (SB12) and sodium N-tetradecyl-N,N-dimethyl-3-amino-1-propane sulfonate (SB14) was studied with electrophoretic methods. The membranes were prepared by osmotic lysis of the cells and depleted of the bulk of extrinsic proteins. It was possible to extract up to 35 and 45% of membrane proteins with SB12 and SB14, respectively. Maximal yield was obtained in both cases with detergent concentrations greater than or equal to 5 mumoles/mg of membrane protein. Spiralin, the major protein in the S. citri membrane, was highly selectively solubilized without the loss of antigenicity, with a yield of about 90% with SB12 and close to 100% with SB14, for a detergent concentration greater than or equal to 0.2 M. The degree of selectivity in favour of spiralin was higher with SB12 (purity approximately equal to 70%) than with SB14 (purity approximately equal to 50%). Treatment of the S. citri membrane with high concentrations of SB12 is a simple and fast procedure for partial purification of spiralin. This example shows that, in some cases, it should be possible to modulate the selectivity of the extraction of membrane proteins simply by varying the relative concentration of detergent.

Bacterial Outer Membrane Proteins↗
PubMed2003

New pinch-porphyrin complexes with quantum mixed spin ground state S=3/2,5/2 of iron (III) and their catalytic activity as peroxidase.

New complexes of the pinch-porphyrin family were obtained from the dimethylester of (proto-, meso-, and deutero-porphyrinato)iron(III) with the ligand [N,N'-bis-pyridin-2-ylmethyl-propane-1,3-diamine] 1-3 and with the ligand [N-pyridin-2-ylmethyl-N'-[3-[(pyridin-2-ylmethyl)-amino]-propyl]-propane-1,3-diamine] 4-6. The UV/VIS studies of 1-6 indicate an increase in the distortion of the ligand field excited state. The 1H NMR spectra of 1-6 at RT and over the range 223-328 K show iron(III)-complexes with quantum mixed spin state (qms) S=5/2, S=3/2. The chemical shifts of the meso protons are consistent with qms state S=3/2, S=5/2, where the S=3/2 spin state is lowest in energy. For methyl-heme the chemical shifts are also consistent with a qms state but now the S=5/2 ground state is lowest in energy. ESR spectra of 1-6 show two different species, B and C, of iron(III) with qms, S=5/2, S=3/2 consistent with the 1H NMR results. Species B with 70% of S=5/2 and species C with 72.5% of S=3/2. The catalytic activity as peroxidase of 1-6 was quantified by guaiacol test; their theoretical maximum rate constants were k(cat) approximately 10(2)-10(3) M(-1) s(-1). A quantitative empirical correlation is found: the higher the 32 spin contribution to the qms state and the higher proportion of this species into the samples, the higher the peroxidase activity. Such a correlation was also obtained for pinch-porphyrins already reported.

Catalysis↗
PubMed1997

Measurement of dexfenfluramine metabolism in rat liver microsomes by gas chromatography-mass spectrometry.

A specific and useful method was developed for the determination of dexfenfluramine metabolism by microsomal systems utilising GC-MS. The synthesis of two metabolites 1-(3-trifluoromethylphenyl)propan-2-ol ('alcohol') and 1-(3-trifluoromethylphenyl)-1,2-propanediol ('diol') via straightforward routes, were confirmed by MS and NMR spectra. The conditions for extraction from alkalinised microsomal mixtures of the metabolites nordexfenfluramine, 1-(3-trifluoromethylphenyl)propan-2-one ('ketone'), alcohol and diol, their conversion to trifluoroacetate derivatives and analysis by GC-MS-SIM are described. Calibration curves were constructed between 48 and 9662 nM and fitted to quadratic equations (r2>0.999). The method precision was good over low (121 nM) medium (2415 nM) and above medium (9662 nM) concentrations for all metabolites; the within- and day-to-day coefficients of variation ranged between 2.5-12.4% and 6.7-17.5%, respectively. The accuracy, measured as bias, was very good both within- and day-to-day (range: -0.4-12.6%, 0.8-18.9%). For most metabolites, the C.V. for the assay and bias increased at 121 nM. Dexfenfluramine metabolism by rat liver microsomes was investigated using the assay method and showed a concentration dependent increase in nordexfenfluramine and ketone metabolites over the substrate range of 5-200 microM.

Animals↗
PubMed1997

Strategies for the aerobic co-metabolism of chlorinated solvents.

Recent field and laboratory studies have evaluated the potential for aerobic co-metabolism of chlorinated solvents. Different co-metabolic substrates and different methods of application have been tried, including growing indigenous microbes in situ, and injecting into the soil subsurface strains grown in subsurface reactors for their co-metabolic potential. There is much potential for using co-metabolism for treating a broad range of chlorinated aliphatic hydrocarbons. Recirculation wells have potential for adding soluble co-metabolic substrates (i.e. phenol and toluene) into contaminated aquifers, while direct addition of gaseous substrates (i.e. methane and propane) into aquifers also holds promise. Aromatic substrates (phenol and toluene) are best used for treatment of chlorinated ethenes, whereas gaseous co-metabolic substrate (methane and propane) are better suited for the treatment of chlorinated methanes and ethanes. Many factors can enhance co-metabolic transformations, such as nutrients and available energy sources.

Aerobiosis↗
PubMed2001

Synthesis and preliminary biological characterization of a new potential (125)I-radioligand for dopamine and serotonin receptors.

The synthesis and a preliminary biological characterization of a new class of N-benzyl-aminoalcohols which have serotonin (5-HT(2)) and dopamine (D(2)) receptor affinity is described. In vitro competition binding studies were conducted with the new molecules and (3)H-spiperone on crude membrane preparation from rat striatum and frontal cortex. One of these compounds, 3-benzylamino-1-(4-fluoro-2-iodophenyl)-propan-1-ol (6f), whose IC(50) values are in the micromolar range for both the D(2) and 5-HT(2) receptors, was prepared in iodine-125 labelled form (6i) by nucleophilic substitution of the bromine atom of 3-benzylamino-1-(2-bromo-4-fluorophenyl)-propan-1-ol (6d). In the in vivo studies, conducted on rats, the radiolabelled molecule 6i shows a good capacity to cross the blood-brain barrier (BBB) with a mean value of first pass cerebral extraction (E) of ca. 50% when the regional cerebral blood flow, measured with microsphere technique, is in the experimental animal's physiologic range (0.8-1 mL/min/g). A preliminary in vitro autoradiographic distribution on coronal rat brain slices of the radioiodinated molecule showed that it was preferentially localized in the striatum and in the cerebral regions rich in dopamine- and serotonin receptors, even if a high non-specific binding was observed.

Animals↗
PubMed2003

Fully automated synthesis of O-(3-[18F]fluoropropyl)-L-tyrosine by direct nucleophilic exchange on a quaternary 4-aminopyridinium resin.

A fully automated synthesis of O-(3-[18F]fluoropropyl)-L-tyrosine (FPT), an amino acid tracer for tumor imaging with positron emission tomography, is described. FPT was prepared by a two-step reaction sequence. Direct nucleophilic fluorination substitution of [18F]fluoride with 1,3-di(4-methylphenylsulfonyloxy)propane on a quaternary 4-(4-methylpiperidinyl)pyridinium functionalized polystyrene anion exchange resin, followed by [18F]fluoro-1-(4-methylphenylsulfonyloxy)propane yielded FPT. The overall radiochemical yield with no decay correction was about 12%; the whole synthesis time was about 52 min, and the radiochemical purity was above 95%.

Anion Exchange Resins↗
PubMed2003

Mixing apparatus for preparing NMR samples under pressure.

The size limit for protein NMR spectroscopy in solution arises in large part from line broadening caused by slow molecular tumbling. One way to alleviate this problem is to increase the effective tumbling rate by reducing the viscosity of the solvent. Because proteins generally require an aqueous environment to remain folded, one approach has been to encapsulate hydrated proteins in reverse micelles formed by a detergent and to dissolve the encapsulated protein in a low-viscosity fluid. The high volatility of suitable low-viscosity fluids requires that the samples be prepared and maintained under pressure. We describe a novel apparatus used for the preparation of such samples. The apparatus includes a chamber for mixing the detergent with the low-viscosity solvent, a second chamber for mixing this with hydrated protein, and a 5-mm (o.d.) zirconium oxide NMR sample tube with shut-off valves designed to contain pressures on the order of 10 bar, sufficient for liquid propane. Liquids are moved from one location to another by introducing minor pressure differentials between two pressurization vessels. We discuss the operation of this apparatus and illustrate this with data on a 30-kDa protein complex (chymotrypsin:turkey ovomucoid third domain) encapsulated in reverse micelles of the detergent, sodium bis (2-ethylhexyl) sulfosuccinate, aerosol-ot (AOT), dissolved in liquid propane.

Animals↗
PubMed2002

A fatal case considered to be due to cardiac arrhythmia associated with butane inhalation.

An autopsy case of a 14-year-old boy whose death is considered to be a result of cardiac arrhythmia after butane inhalation and sample preservation for butane analysis are reported. The electrocardiogram taken in the ambulance revealed ventricular fibrillation. There were no autopsy findings as to the cause of death. n-Butane, isobutane and propane were identified in the blood, brain and lung of the cadaver by headspace gas chromatography. Based on these results, the cause of death was concluded to be cardiac arrhythmia due to butane inhalation. As a follow-up, n-butane, isobutane and propane concentrations in the blood kept at -30 degrees C showed the unchanged values with a coefficient of variation of within 10% for 2 weeks.

Journal Article↗
PubMed2000

Reactions of hydroxyl radicals with alkenes in low-temperature matrices.

The reactions of hydroxyl radicals with a number of stable alkenes have been studied in low-temperature matrices. The reactions were initiated by broad band UV-visible irradiation of matrices containing H2O2, and the alkene under investigation. The hydroxyalkyl radical products were identified principally by comparison of their spectra with the spectra of corresponding stable alcohols. Accordingly, IR spectra were recorded for the following series of alcohols isolated in argon matrices--methanol, ethanol, ethanol-d6, propan-1-ol, propan-2-ol, butan-2-ol, 2-methylpropan-1-ol (iso-butyl alcohol), 2-methylpropan-2-ol (tert-butyl alcohol), 2-methylbutan-2-ol (tert-amyl alcohol), 3-methylbutan-2-ol and 2,3-dimethylbutan-2-ol. The hydroxyalkyl radicals, which appear to be formed from the alkenes studied were as follows--from ethene, 2-hydroxyethyl radical: from cis- or trans-but-2-ene. 1-methyl-2-hydroxypropyl radical; from propene, 1-methyl-2-hydroxyethyl and 2-hydroxypropyl radicals; from but-1-ene. 1-hydroxymethylpropyl and 2-hydroxybutyl radicals; from 2-methylpropene (iso-butene), 1,1-dimethyl-2-hydroxyethyl and 2-methyl-2-hydroxypropyl radicals; the radical products from buta-1,3-diene and isoprene could not be identified. In the cases, where two radical products were possible, i.e. when propene, but-1-ene or 2-methylpropene were the substrates, it was found that the concentration of the secondary or tertiary radical always exceeded that of the primary radical. However, the relative concentration of these radicals appears to be determined by subsequent photolysis to give carbonyl compounds. There seems, therefore, to be little preference for the secondary and tertiary radicals over the primary radicals in the primary addition process. Comments on the mechanism of the transformation from radical to carbonyl compound based upon identification of intermediates within the matrix and isotopic substitution experiments are made. The characterisation of the 2-hydroxyethyl radical has been backed up by experiments utilising isotopic substitution with 13C and D (2H). The other radicals have been identified with varying degrees of certainty. Those radicals, which are observed at the highest concentration and which are, therefore, characterised more certainly are--2-hydroxyethyl (1), from ethene: 1-methyl-2-hydroxypropyl (2), from cis- and trans-but-2-ene; 1-methyl-2-hydroxyethyl (3), from propene; 1-hydroxymethylpropyl (5), from but-1-ene; and 1,1- dimethyl-2-hydroxyethyl (8), from 2-methylpropene.

Alcohols↗
PubMed2003

Studies of solvation in homogeneous and heterogeneous media by electronic spectroscopic method.

Solvation characteristics in homogenous (pure and mixed binary solvents) and heterogeneous media (aqueous micelles, beta- and gamma-cyclodextrine solutions) have been studied by monitoring the emission characteristics of a newly synthesised dye. The longest wavelength absorption and emission band of the dye arise due to transition between S(0) and S(1) state. The maximum energy of electronic transition involving intramolecular charge transfer is found to be dependent on both the hydrogen-bond donating ability and the polarity-polarisability in pure solvent. The dipole moment in the S(1) state, as determined by solvatochromic procedure, agrees well with the value obtained by theoretical calculation at the AM1 level. Preferential solvation of the dye by alcohols has been found to occur in ethanol+water, propan-1-ol+water, propan-2-ol+water binary mixtures. In aqueous micellar media the dye molecule is located at the water-micelle interface. The binding constant for the dye-micelle interaction has also been determined. The results have been compared with those for a structurally related symmetrical ketocyanine dye.

Calorimetry↗
PubMed2004

Preferential solvation of Brooker's merocyanine in binary solvent mixtures composed of formamides and hydroxylic solvents.

The ET polarity values of 4-[(1-methyl-4(1H)-pyridinylidene)-ethylidene]-2,5-cyclohexadien-1-one (Brooker's merocyanine) were collected in mixed-solvent systems comprising a formamide [N,N-dimethylformamide (DMF), N-methylformamide (NMF) or formamide (FA)] and a hydroxylic (water, methanol, ethanol, propan-2-ol or butan-1-ol) solvent. Binary mixtures involving DMF and the other formamides (NMF and FA) as well as NMF and FA were also studied. These data were employed in the investigation of the preferential solvation (PS) of the probe. Each solvent system was analyzed in terms of both solute-solvent and solvent-solvent interactions. These latter interactions were responsible for the synergism observed in many binary mixtures. This synergistic behaviour was observed for DMF-propan-2-ol, DMF-butan-1-ol, FA-methanol, FA-ethanol and for the mixtures of the alcohols with NMF. All data were successfully fitted to a model based on solvent-exchange equilibria, which allowed the separation of the different contributions of the solvent species in the solvation shell of the dye. The results suggest that both hydrogen bonding and solvophobic interactions contribute to the formation of the solvent complexes responsible for the observed synergistic effects in the PS of the dye.

1-Butanol↗
PubMed1986

Inactivation of Escherichia coli glycerol kinase by 5,5'-dithiobis(2-nitrobenzoic acid) and N-ethylmaleimide: evidence for nucleotide regulatory binding sites.

Glycerol kinase (EC 2.7.1.30, ATP:glycerol 3-phosphotransferase) from Escherichia coli is inactivated by 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) and by N-ethylmaleimide (NEM) in 0.1 M triethanolamine at pH 7 and 25 degrees C. The inactivation by DTNB is reversed by dithiothreitol. In the cases of both reagents, the kinetics of activity loss are pseudo first order. The dependencies of the rate constants on reagent concentration show that while the inactivation by NEM obeys second-order kinetics (k2app = 0.3 M-1 s-1), DTNB binds to the enzyme prior to the inactivation reaction; i.e., the pseudo-first-order rate constant shows a hyperbolic dependence on DTNB concentration. Complete inactivation by each reagent apparently involves the modification of two sulfhydryl groups per enzyme subunit. However, analysis of the kinetics of DTNB modification, as measured by the release of 2-nitro-5-thiobenzoate, shows that the inactivation is due to the modification of one sulfhydryl group per subunit, while two other groups are modified 6 and 15 times more slowly. The enzyme is protected from inactivation by the ligands glycerol, propane-1,2-diol, ATP, ADP, AMP, and cAMP but not by Mg2+, fructose 1,6-bisphosphate, or propane-1,3-diol. The protection afforded by ATP or AMP is not dependent on Mg2+. The kinetics of DTNB modification are different in the presence of glycerol or ATP, despite the observation that the degree of protection afforded by both of these ligands is the same.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed1988

Isolation and purification of an Fc epsilon receptor activated ion channel from the rat mast cell line RBL-2H3.

Derivatives of the antiallergic drug cromolyn [disodium 5,5'-[(2-hydroxy-1,3-propanediyl)-bis(oxy)]bis [4-oxo-(4H-1-benzopyran)-2- carboxylate]], which can be conjugated covalently at the propane 2-position to macromolecules and to insoluble matrices, were synthesized. Conjugates of these derivatives with macromolecules were examined for their binding to cells of the rat basophilic leukemia line RBL-2H3, which is widely employed as a model for immunologically induced mast cell degranulation. Only those drug-protein conjugates in which the cromolyn analogue with an amino group at the propane 2-carbon instead of the hydroxyl was linked to the carrier by glutaraldehyde were found to exhibit specific and saturable binding to these cells. Analysis of the binding data for these conjugates yielded an apparent binding constant of 3.8 +/- 0.2 X 10(8) M-1 and an apparent number of binding sites for the probe of 4000-8000 per cell. The conjugates found to bind specifically to the cells were also immobilized on agarose matrices and employed in an affinity-based isolation of the membrane component responsible for the observed binding. A single labeled polypeptide was eluted from these columns, onto which either whole cell lysates or solubilized purified plasma membranes of surface-radioiodinated RBL-2H3 cells had been adsorbed. This membrane protein appears on autoradiograms of nonreducing SDS-PAGE as a single broad band of approximately 110,000 daltons (Da) apparent molecular mass. On autoradiograms of reducing gels, the only band detected has an apparent mass of approximately 50,000 Da and appears narrower. Elution of the columns with the drug and disulfide-reducing agents or with the latter alone resulted in significantly higher yields of the 50-kDa polypeptide. Both the intact and reduced proteins bind strongly to immobilized concanavalin A and less so to immobilized wheat germ agglutinin, suggesting that the isolated intact protein is probably a dimer of two glycosylated subunits of similar molecular mass. Treatment of the reduced protein with endoglycosidase F leads to a decrease in its apparent molecular mass by approximately 12 kDa, suggesting that the extent of glycosylation of this polypeptide is approximately 25%. As shown in the following paper, the intact protein constitutes a Ca2+ channel that is activated upon IgE-Fc epsilon receptor aggregation.

Affinity Labels↗
PubMed1998

Sugars and polyols inhibit fibrillogenesis of type I collagen by disrupting hydrogen-bonded water bridges between the helices.

To better understand the mechanism of collagen fibrillogenesis, we studied how various sugars and polyols affect the formation and stability of collagen fibers. We combined traditional fiber assembly assays with direct measurement of the interaction between collagen triple helices in fibers by osmotic stress and X-ray diffraction. We found that the effects of sugars and polyols were highly specific with respect to small structural differences between these solutes. For example, 1,2-propane diol only weakly inhibited the fiber assembly and practically did not affect the interaction between collagen helices in fibers. At the same concentration, 1,3-propane diol eliminated the attraction between collagen helices and strongly suppressed fibrillogenesis. The two diols have the same atomic composition and differ only by the position of one of their hydroxyls. Still, their ability to inhibit fiber assembly differs by more than an order of magnitude, as judged by protein solubility. We argue that this is because collagen fibrillogenesis requires formation of hydrogen-bonded water clusters bridging recognition sites on the opposing helices. The ability of various sugars and polyols to inhibit the fiber assembly and to destabilize existing fibers is determined by how efficiently these solutes can compete with water for crucial hydrogen bonds and, thus, disrupt the water bridges. The effect of a sugar or a polyol appears to be strongly dependent on the specific stereochemistry of the solute hydroxyls that defines the preferred hydrogen-bonding pattern of the solute.

Ampholyte Mixtures↗
PubMed1999

Structural and kinetic determinants of aldehyde reduction by aldose reductase.

Aldose reductase (AR) is a member of the aldo-keto reductase superfamily. Due to its ability to catalyze the formation of sorbitol from glucose during hyperglycemic and hypertonic stress, the aldose-reducing property of AR has been accepted as its main physiological and pathological function. Nonetheless, AR is a poor catalyst for glucose reduction and displays active-site properties unexpected of a carbohydrate-binding protein. We, therefore, examined the catalytic properties of AR with a series of naturally occurring aldehydes, compatible in their hydrophobicity to the large apolar active site of the enzyme. Our results show that recombinant human AR is an efficient catalyst for the reduction of medium- to long-chain unbranched saturated and unsaturated aldehydes. The enzyme displayed selective preference for saturated aldehydes, such as hexanal, and unsaturated aldehydes, such as trans-2-octenal and nonenal as well as their 4-hydroxy derivatives. Short-chain aldehydes such as propanal and acrolein were reduced less efficiently. Branched derivatives of acrolein or its glutathione conjugate (GS-propanal) were, however, reduced with high efficiency. In the absence of NADPH, the alpha, beta unsaturated aldehydes caused covalent modification of the enzyme. On the basis of electrospray mass spectrometric analysis of the wild-type and site-directed mutants of AR (in which the solvent exposed cysteines were individually replaced with serine), the site of modification was identified to be the active-site residue, Cys 298. The unsaturated aldehydes, however, did not modify the enzyme bound to NADPH and did not inactivate the enzyme during catalysis. Modeling studies indicate that the large hydrophobic active site of AR can accommodate a large number of aldehydes without changes in the structure of the binding site or movement of side chains. High hydrophobicity due to long alkyl chains or apolar substituents appears to stabilize the interaction of the aldehyde substrates with the enzyme. Apparently, such hydrophobic interactions provide substrate selectivity and catalytic efficiency of the order achievable by hydrogen bonding. Since several of the aldehydes reduced by AR are either environmental and pharmacological pollutants or products of lipid peroxidation, the present studies provide the basis of future investigations on the role of AR in regulating aldehyde metabolism particularly under pathological states associated with oxidative stress and/or aldehyde toxicity.

Aldehyde Reductase↗