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Several aldehyde dehydrogenase (ALDH) complexes have been purified from the membranes of acetic acid bacteria. The enzyme structures and the chemical nature of the prosthetic groups associated with these enzymes remain a matter of debate. We report here on the molecular and catalytic properties of the membrane-bound ALDH complex of the diazotrophic bacterium Gluconacetobacter diazotrophicus. The purified ALDH complex is a heterodimer comprising two subunits of 79.7 and 50 kDa, respectively. Reversed-phase high-pressure liquid chromatography (HPLC) and electron paramagnetic resonance spectroscopy led us to demonstrate, for the first time, the unequivocal presence of a pyrroloquinoline quinone prosthetic group associated with an ALDH complex from acetic acid bacteria. In addition, heme b was detected by UV-visible light (UV-Vis) spectroscopy and confirmed by reversed-phase HPLC. The smaller subunit bears three cytochromes c. Aliphatic aldehydes, but not formaldehyde, were suitable substrates. Using ferricyanide as an electron acceptor, the enzyme showed an optimum pH of 3.5 that shifted to pH 7.0 when phenazine methosulfate plus 2,6-dichlorophenolindophenol were the electron acceptors. Acetaldehyde did not reduce measurable levels of the cytochrome b and c centers; however, the dithionite-reduced hemes were conveniently oxidized by ubiquinone-l; this finding suggests that cytochrome b and the cytochromes c constitute an intramolecular redox sequence that delivers electrons to the membrane ubiquinone. doi: 10.1128/JB.00589-10

The hyperthermophilic archaeon Pyrococcusfuriosus expresses five aldehyde oxidoreductase (AOR) enzymes, all containing a tungsto-bispterin cofactor. The growth of this organism is fully dependent on the presence of tungsten in the growth medium. Previous studies have suggested that molybdenum is not incorporated in the active site of these enzymes. Application of the radioisotope [sup.99]Mo in metal isotope native radioautography in gel electrophoresis (MIRAGE) technology to P. furiosus shows that molybdenum can in fact be incorporated in all five AOR enzymes. Mo(V) signals characteristic for molybdopterin were observed in formaldehyde oxidoreductase (FOR) in electron paramagnetic resonance (EPR)-monitored redox titrations. Our finding that the aldehyde oxidation activity of FOR and WOR5 (W-containing oxidoreductase 5) correlates only with the residual tungsten content suggests that the Mo-containing AORs are most likely inactive. An observed W/Mo antagonism is indicative of tungstate-dependent negative feedback of the expression of the tungstate/molybdate ABC transporter. An intracellular selection mechanism for tungstate and molybdate processing has to be present, since tungsten was found to be preferentially incorporated into the AORs even under conditions with comparable intracellular concentrations of tungstate and molybdate. Under the employed growth conditions of starch as the main carbon source in a rich medium, no tungsten- and/or molybdenum-associated proteins are detected in P. furiosus other than the high-affinity transporter, the proteins of the metallopterin insertion machinery, and the five W-AORs. doi: 10.1128/JB.00270-10

TRPA1 is an excitatory ion channel expressed by a subpopulation of primary afferent somatosensory neurons that contain substance P and calcitonin gene-related peptide. Environmental irritants such as mustard oil, allicin, and acrolein activate TRPA1, causing acute pain, neuropeptide release, and neurogenic inflammation. Genetic studies indicate that TRPA1 is also activated downstream of one or more proalgesic agents that stimulate phospholipase C signaling pathways, thereby implicating this channel in peripheral mechanisms controlling pain hypersensitivity. However, it is not known whether tissue injury also produces endogenous proalgesic factors that activate TRPA1 directly to augment inflammatory pain. Here, we report that recombinant or native TRPA1 channels are activated by 4-hydroxy-2-nonenal (HNE), an endogenous [alpha],[beta]-unsaturated aldehyde that is produced when reactive oxygen species peroxidate membrane phospholipids in response to tissue injury, inflammation, and oxidative stress. HNE provokes release of substance P and calcitonin gene-related peptide from central (spinal cord) and peripheral (esophagus) nerve endings, resulting in neurogenic plasma protein extravasation in peripheral tissues. Moreover, injection of HNE into the rodent hind paw elicits pain-related behaviors that are inhibited by TRPA1 antagonists and absent in animals lacking functional TRPA1 channels. These findings demonstrate that HNE activates TRPA1 on nociceptive neurons to promote acute pain, neuropeptide release, and neurogenic inflammation. Our results also provide a mechanism-based rationale for developing novel analgesic or anti-inflammatory agents that target HNE production or TRPA1 activation. oxidative stress | sensory signaling | TRP channel | nociception

Alcohol is eliminated from the body by various metabolic mechanisms. The primary enzymes involved are aldehyde dehydrogenase (ALDH), alcohol dehydrogenase (ADH), cytochrome P450 (CYP2E1), and catalase. Variations in the genes [...]

Aldehyde dehydrogenase (ALDH) is an enzyme that is expressed in the liver and is required for the conversion of retinol (vitamin A) to retinoic acids. ALDH is also highly enriched in hematopoietic stem cells (HSCs) and is considered a selectable marker of human HSCs, although its contribution to stem cell fate remains unknown. In this study, we demonstrate that ALDH is a key regulator of HSC differentiation. Inhibition of ALDH with diethylaminobenzaldehyde (DEAB) delayed the differentiation of human HSCs that otherwise occurred in response to cytokines. Moreover, short-term culture with DEAB caused a 3.4-fold expansion in the most primitive assayable human cells, the nonobese diabetic/severe combined immunodeficiency mouse repopulating cells, compared with day 0 CD[34.sup.+]CD[38.sup.-][lin.sup.-] cells. The effects of DEAB on HSC differentiation could be reversed by the coadministration of the retinoic acid receptor agonist, all-trans-retinoic acid, suggesting that the ability of ALDH to generate retinoic acids is important in determining HSC fate. DEAB treatment also caused a decrease in retinoic acid receptor-mediated signaling within human HSCs, suggesting directly that inhibition of ALDH promotes HSC self-renewal via reduction of retinoic acid activity. Modulation of ALDH activity and retinoid signaling is a previously unrecognized and effective strategy to amplify human HSCs. retinoic acid | self-renewal | diethylaminobenzaldehyde | long-term repopulating cells

The amino acid [beta]-alanine is an intermediate in pantothenic acid (vitamin [B.sub.5]) and coenzyme A (CoA) biosynthesis. In contrast to bacteria, yeast derive the [beta]-alanine required for pantothenic acid production via polyamine metabolism, mediated by the four SPE genes and by the FAD-dependent amine oxidase encoded by FMS1. Because amine oxidases generally produce aldehyde derivatives of amine compounds, we propose that an additional aldehyde-dehydrogenase-mediated step is required to make [beta]-alanine from the precursor aldehyde, 3-aminopropanal. This study presents evidence that the closely related aldehyde dehydrogenase genes ALD2 and ALD3 are required for pantothenic acid biosynthesis via conversion of 3-aminopropanal to [beta]-alanine in vivo. While deletion of the nuclear gene encoding the unrelated mitochondrial Ald5p resulted in an enhanced requirement for pantothenic acid pathway metabolites, we found no evidence to indicate that the Ald5p functions directly in the conversion of 3-aminopropanal to [beta]-alanine. Thus, in Saccharomyces cerevisiae, ALD2 and ALD3 are specialized for [beta]-alanine biosynthesis and are consequently involved in the cellular biosynthesis of coenzyme A.

Research has been conducted on ubiquitin-specific processing protease family of deubiquitinating enzymes. The crystal structure of the catalytic core domain of ubiquitin-specific processing protease family representative HAUSP has been stidied both in isolation and in complex with ubiquitin aldehyde, and the details are reported.

Research has been conducted on phosphonoacetaldehyde hydrolase from Bacillus cereus. This hydrolase catalyzes hydrolytic P-C bond phosphonoacetaldehyde cleavage via Schiff base intermediate formed with Lys53 and the results indicate that ligand binding and dissociation occur from the open conformer and catalysis occurs from the closed conformer.

Research has been conducted on the polymer-supported aldehyde. The synthesis of this aldehyde as a Garner aldehyde equivalent is described.

Research has been conducted on the electrotelluration process. The use of Michael addition of aryl or alkyl tellurolate anion to alkyne and the trapping of a vinyl anion with aldehydes and ketones is described.

Research has been conducted on the beta-hydroxylamino imides. The synthesis of these compounds derived from D-glyceraldehyde has been carried out via the use of various Lewis acids and the details are reported.

Research has been conducted on the acetophenone and benzaldehyde oximes. The study of the oximes' orthoplatination carried out via platinum(II) sulfoxide and sulfide complexes in producing platinacycles is presented.

Research has been conducted on the TiCl (sub)4 -mediated Baylis-Hillman reaction of cyclohexenone with benzaldehydes. Results indicate that the reaction mechanism involves alpha-chloromethyl enone formation as an intermediate.

Research has been conducted on 2-ethoxy-2-(phenylselenyl)perfluoroalk-2-enenitriles. The preparation of these compounds has been carried out and the results indicate that the compounds undergo transmetalation on treatment with n-BuLi or EtMgBr.

Research has been conducted on the reaction of 3-phenylbutyraldehyde or 3-phenylpropionaldehyde with P450 (sub) BM3 -F87G carried out in the presence of hydrogen peroxide. The putative isoporphyrin intermediate produced by this reaction has been investigated via the use of the electron paramagnetic resonance spectroscopy and the details are reported.

Research has been conducted on the topaquinone discovered in copper amine oxidases. The role of this oxidase in the primary amines and molecular oxygen conversion to aldehydes and hydrogen peroxide has been examined and the results are reported.

Research has been conducted on the hydrotris(pyrazolyl)-borate complexes. The preparation and structural characterization of these complexes have been carried out and their reaction with PhC (sub)2 H, 4-NO (sub)2 C (sub)6 H (sub)4 -CHO and Ph (sub)3 SnH is described.

Research has been conducted on bismuth triflate. The use of this compound as a catalyst for conversion of aldehydes and ketones to acetals is described.

Research has been conducted on the tetra-N-confused cyclohexapyrrole. The synthesis of this compound has been carried out via tripyrrinone-aldehyde condensation with bis(2,4-dimethylpyrrole-3-yl)methane in the presence of p-toluenesulfonic acid monohydrate.

Research has been conducted on the catalytic asymmetric acyl halide-aldehyde cyclocondensation reaction. The implementation of the reaction design is described and the results indicate that the reaction strategy allows to employ differentially substituted organocuprates in the 4-substituted 2-oxetanone ring opening.

Research has been conducted on aldehyde dehydrogenases. The two forms of these dehydrogenases and the effect of the tail and several residues from the dimer-dimer interface on the quaternary structure of aldehyde dehydrogenases have been investigated and are reported.

The authors review the publications on the chemical reactivity and biological activity of various functional groups. The topics of interest include the chemical reactivity of nitro, amino, olefinic, hydroxy and carboxaldehyde functional groups.

Research has been conducted on the beta-ketols and alpha,beta-alkenones. The synthesis of these compounds performed via the beta-ketoacid Knoevenagel condensation with aldehyde in aqueous medium is discussed.

Research has been conducted on the C-glycosyl amino acids. The synthesis of N-flycosyl asparagines' ethylene isosteres centered on the metalated sugar acetylene coupling with the Garner aldehydes has been developed and is described.

Research has been conducted on the tricalixarenes and pentacalixarenes. The synthesis of these arenes from O-alkylcalixarene mono- and dialdehydes carried out via the two-step conversion to the monoethylketones and via aryne trimerization in refluxing N,N-dimethylformamide is described.

Research has been conducted on the allenyl-aldehydes and -ketones. The arylative cyclization of these compounds carried out in producing homoallylic cyclopentanols and cyclohexanols via indium-mediated and palladium-catalyzed Babier allylation is described.

Research has been conducted on the aldols which correspond to the C(13)-C(25) segment of bafilomycin A (sub)1. The development of the stereoselective syntheses of these aldols via the chiral aldehyde's fragment assembly aldol reactions is discussed.

Research has been conducted on the allyl metal reagents. The additions of these reagents to benzaldehydes have been investigated and the results are reported.

Research has been conducted on the Fischer carbene complexes. The couplings of these complexes with 3-alkynyl-2-heteroaromatic carboxaldehyde derivatives have been investigated and the results indicate that the reactions produce pyrones fused to thiophenes or furans.

Research has been conducted on the Z-alpha,beta-unsaturated amides. The results of the Peterson reaction of the (triphenylsilyl)acetamide with different aromatic aldehydes are discussed.

Research has been conducted on the alpha-aminoorganostannanes. The development of the N-Boc-N-tert-butylthiomethyl-protected alpha-aminoorganostannanes as precursors to primary amines is reported.

Research has been conducted on the tert-butyl imines of o-(1-alkenyl)benzaldehydes and analogues. Results indicate that the electrophilic cyclization of these imines provides the synthesis of a variety of substituted isoquinolines.

Research has been conducted on the ethyl alpha-fluoro silyl enol ether. The results of the stereoselective synthesis of this ether from the chlorofluoroacetate and Mg or Zn in DMF are presented.

Research has been conducted on the 3,3,3-trifluoropropenyl compounds. The synthesis of these compounds carried out via the TBAF-mediated Horner reaction is discussed.