scispace - formally typeset
Search or ask a question

Showing papers on "Aldehyde dehydrogenase published in 2008"


Journal ArticleDOI
12 Sep 2008-Science
TL;DR: Using an unbiased proteomic search, mitochondrial aldehyde dehydrogenase 2 (ALDH2) is identified as an enzyme whose activation correlates with reduced ischemic heart damage in rodent models and pharmacologic enhancement of ALDH2 activity may be useful for patients with wild-type or mutant AL DH2 who are subjected to cardiac ischemia.
Abstract: There is substantial interest in the development of drugs that limit the extent of ischemia-induced cardiac damage caused by myocardial infarction or by certain surgical procedures. Here, using an unbiased proteomic search, we identified mitochondrial aldehyde dehydrogenase 2 (ALDH2) as an enzyme whose activation correlates with reduced ischemic heart damage in rodent models. A high-throughput screen yielded a small-molecule activator of ALDH2 (Alda-1) that, when administered to rats before an ischemic event, reduced infarct size by 60%, most likely through its inhibitory effect on the formation of cytotoxic aldehydes. In vitro, Alda-1 was a particularly effective activator of ALDH2*2, an inactive mutant form of the enzyme that is found in 40% of East Asian populations. Thus, pharmacologic enhancement of ALDH2 activity may be useful for patients with wild-type or mutant ALDH2 who are subjected to cardiac ischemia, such as during coronary bypass surgery.

666 citations


Journal ArticleDOI
TL;DR: What is currently known about each member of the human ALDH superfamily, composed of NAD(P)+-dependent enzymes that catalyze aldehyde oxidation, is presented including the pathophysiological significance of these enzymes.
Abstract: Background: Aldehydes are highly reactive molecules. While several non-P450 enzyme systems participate in their metabolism, one of the most important is the aldehyde dehydrogenase (ALDH) superfamily, composed of NAD(P)+-dependent enzymes that catalyze aldehyde oxidation. Objective: This article presents a review of what is currently known about each member of the human ALDH superfamily including the pathophysiological significance of these enzymes. Methods: Relevant literature involving all members of the human ALDH family was extensively reviewed, with the primary focus on recent and novel findings. Conclusion: To date, 19 ALDH genes have been identified in the human genome and mutations in these genes and subsequent inborn errors in aldehyde metabolism are the molecular basis of several diseases, including Sjogren-Larsson syndrome, type II hyperprolinemia, γ-hydroxybutyric aciduria and pyridoxine-dependent seizures. ALDH enzymes also play important roles in embryogenesis and development, neurotransmissi...

651 citations


Journal ArticleDOI
TL;DR: Comparing protein profiles between CD133+ and CD133− subpopulations isolated from Huh7 and PLC8024 and identifying aldehyde dehydrogenase 1A1 as one of the proteins that are preferentially expressed in theCD133+ subfraction reveals the existence of a hierarchical organization in HCC bearing tumorigenic potential in the order of CD133+.
Abstract: Recent efforts in our study of cancer stem cells (CSC) in hepatocellular carcinoma (HCC) have led to the identification of CD133 as a prominent HCC CSC marker. Findings were based on experiments done on cell lines and xenograft tumors where expression of CD133 was detected at levels as high as 65%. Based on the CSC theory, CSCs are believed to represent only a minority number of the tumor mass. This is indicative that our previously characterized CD133+ HCC CSC population is still heterogeneous, consisting of perhaps subsets of cells with differing tumorigenic potential. We hypothesized that it is possible to further enrich the CSC population by means of additional differentially expressed markers. Using a two-dimensional PAGE approach, we compared protein profiles between CD133+ and CD133− subpopulations isolated from Huh7 and PLC8024 and identified aldehyde dehydrogenase 1A1 as one of the proteins that are preferentially expressed in the CD133+ subfraction. Analysis of the expression of several different ALDH isoforms and ALDH enzymatic activity in liver cell lines found ALDH to be positively correlated with CD133 expression. Dual-color flow cytometry analysis found the majority of ALDH+ to be CD133+, yet not all CD133+ HCC cells were ALDH+. Subsequent studies on purified subpopulations found CD133+ALDH+ cells to be significantly more tumorigenic than their CD133−ALDH+ or CD133−ALDH− counterparts, both in vitro and in vivo. These data, combined with those from our previous work, reveal the existence of a hierarchical organization in HCC bearing tumorigenic potential in the order of CD133+ALDH+ > CD133+ALDH− > CD133−ALDH−. ALDH, expressed along CD133, can more specifically characterize the tumorigenic liver CSC population. (Mol Cancer Res 2008;6(7):1146–53)

435 citations


Journal ArticleDOI
TL;DR: The available tools that can impact ALDH activity and may have the potential to be used therapeutically, specifically targeting the CSC are reviewed and questions that need to be investigated are raised.
Abstract: Multiple aldehyde dehydrogenase genes have been identified in many tissues. Aldehyde dehydrogenase class 1A1 (ALDH1A1) has been identified as highly expressed in embryonal tissue as well as in adult stem cells isolated from bone marrow, brain, breast and possibly other tissues. The recent interest in the idea of cancer stem cells (CSC) has resulted in renewed and vigorous interest in aldehyde dehydrogenase activity as a marker for those stem cells as well. It has been known that ALDH activity, which may reflect other ALDH isozymes in addition to ALDH1A1, is important for multiple biological activities including drug resistance, cell differentiation, and oxidative stress response. Purification of viable cells with high ALDH activity has become relatively easy with the availability of flow cytometry based assay. In this review, we examine the data available in regarding the importance of ALDH activity in normal and malignant stem cell functions, and the potential diagnostic and therapeutic implications. We review the available tools that can impact ALDH activity and may have the potential to be used therapeutically, specifically targeting the CSC. We raise questions that need to be investigated before a reasonable therapeutic strategy can be devised that will effectively inhibit ALDH activity.

254 citations


Journal ArticleDOI
TL;DR: Results indicate that this enzyme may have a physiological function by protecting the cell against the toxic effect of aldehydes derived from lipid oxidation, and speculate that in Escherichia coli YqhD is part of a glutathione-independent, NADPH-dependent response mechanism to lipid peroxidation.

210 citations


Journal ArticleDOI
TL;DR: An overview of the current knowledge of genetics, evolution, structure, enzymology, tissue distribution and regulation of mammalian aldehyde oxidases is provided.
Abstract: Mammalian aldehyde oxidases are a small group of proteins belonging to the larger family of molybdo-flavoenzymes along with xanthine oxidoreductase and other bacterial enzymes. The two general types of reactions catalyzed by aldehyde oxidases are the hydroxylation of heterocycles and the oxidation of aldehydes into the corresponding carboxylic acids. Different animal species are characterized by a different complement of aldehyde oxidase genes. Humans contain a single active gene, while marsupials and rodents are characterized by four such genes clustering at a short distance on the same chromosome. At present, little is known about the physiological relevance of aldehyde oxidases in humans and other mammals, although these enzymes are known to play a role in the metabolism of drugs and compounds of toxicological importance in the liver. The present article provides an overview of the current knowledge of genetics, evolution, structure, enzymology, tissue distribution and regulation of mammalian aldehyde oxidases.

171 citations


Journal ArticleDOI
TL;DR: Significant differences of ADH isoenzymes activities between cancer tissues and healthy organs may be a factor intensifying carcinogenesis by the increased ability to acetaldehyde formation from ethanol and disorders in metabolism of some biologically important substances.

157 citations


Journal ArticleDOI
TL;DR: The findings suggest that the alcohol sensitivity quite common in individuals of Mongoloid origin might be due to delayed oxidation of acetaldehyde by an unusual type of ALDH.
Abstract: Electrophoretic and kinetic studies of autopsy liver specimens from individuals of different racial groups revealed a polymorphism in alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). About 85% of the Japanese livers had an atypical ADH and 52% of the livers an unusual ALDH. Only 13% of German liver specimens had the atypical ADH and none showed the unusual form of ALDH which lacks in the isozyme with low Km for acetaldehyde. Using hair roots as the source of ADH and ALDH, individuals showing sensitivity to ethanol were examined. Data on the distribution of phenotypes in random European and Japanese population as well as family studies suggest a direct relationship between the lack of low Km isozyme of ALDH and alcohol-induced biological sensitivity. Our findings suggest that the alcohol sensitivity quite common in individuals of Mongoloid origin might be due to delayed oxidation of acetaldehyde by an unusual type of ALDH.

156 citations


Journal ArticleDOI
TL;DR: Km values for most retinoid-active ADHs and RDHs are close to 1 μM or lower, suggesting that they participate physiologically in retinol/retinaldehyde interconversion.
Abstract: Retinoic acid (RA), the most active retinoid, is synthesized in two steps from retinol. The first step, oxidation of retinol to retinaldehyde, is catalyzed by cytosolic alcohol dehydrogenases (ADHs) of the medium-chain dehydrogenase/reductase (MDR) superfamily and microsomal retinol dehydrogenases (RDHs) of the short-chain dehydrogenase/reductase (SDR) superfamily. The second step, oxidation of retinaldehyde to RA, is catalyzed by several aldehyde dehydrogenases. ADH1 and ADH2 are the major MDR enzymes in liver retinol detoxification, while ADH3 (less active) and ADH4 (most active) participate in RA generation in tissues. Several NAD+- and NADP+-dependent SDRs are retinoid active. Their in vivo contribution has been demonstrated in the visual cycle (RDH5, RDH12), adult retinoid homeostasis (RDH1) and embryogenesis (RDH10). Km values for most retinoid-active ADHs and RDHs are close to 1 μM or lower, suggesting that they participate physiologically in retinol/retinaldehyde interconversion. Probably none of these enzymes uses retinoids bound to cellular retinol-binding protein, but only free retinoids. The large number of enzymes involved in the two directions of this step, also including aldo-keto reductases, suggests that retinaldehyde levels are strictly regulated.

149 citations


Journal ArticleDOI
TL;DR: These molecular effects of the ALDH knock-down are associated with in vitro functional changes in the proliferation and motility of these cells and demonstrate the significance of ALDH enzymes in cell homeostasis with a potentially significant impact on the treatment of lung cancer.
Abstract: Aldehyde dehydrogenase isozymes ALDH1A1 and ALDH3A1 are highly expressed in non small cell lung cancer. Neither the mechanisms nor the biologic significance for such over expression have been studied. We have employed oligonucleotide microarrays to analyze changes in gene profiles in A549 lung cancer cell line in which ALDH activity was reduced by up to 95% using lentiviral mediated expression of siRNA against both isozymes (Lenti 1+3). Stringent analysis methods were used to identify gene expression patterns that are specific to the knock down of ALDH activity and significantly different in comparison to wild type A549 cells (WT) or cells similarly transduced with green fluorescent protein (GFP) siRNA. We confirmed significant and specific down regulation of ALDH1A1 and ALDH3A1 in Lenti 1+3 cells and in comparison to 12 other ALDH genes detected. The results of the microarray analysis were validated by real time RT-PCR on RNA obtained from Lenti 1+3 or WT cells treated with ALDH activity inhibitors. Detailed functional analysis was performed on 101 genes that were significantly different (P < 0.001) and their expression changed by ≥ 2 folds in the Lenti 1+3 group versus the control groups. There were 75 down regulated and 26 up regulated genes. Protein binding, organ development, signal transduction, transcription, lipid metabolism, and cell migration and adhesion were among the most affected pathways. These molecular effects of the ALDH knock-down are associated with in vitro functional changes in the proliferation and motility of these cells and demonstrate the significance of ALDH enzymes in cell homeostasis with a potentially significant impact on the treatment of lung cancer.

142 citations


Journal ArticleDOI
TL;DR: The Aldh organ-specific distribution may be important in elucidating their role in metabolism, elimination, and organ- specific toxicity of xenobiotics, and in contrast to other phase-I metabolic enzymes, Aldh mRNA expression seems to be generally insensitive to typical microsomal inducers except PPAR alpha ligands.

Journal ArticleDOI
TL;DR: It is indicated that the presently evaluated variant alleles in the CYP2B6, CyP2C9, CYP3A4, CYp3A5, GSTA1, GSTP1, ALDH1A1 and ALDH3A1 genes do not explain the interindividual variability in cyclophosphamide and 4-hydroxycyclophosphamate pharmacokinetics and are, probably, not the cause of the observed variability in toxicity.
Abstract: PurposeThe anticancer agent, cyclophosphamide, is metabolized by cytochrome P450 (CYP), glutathione S-transferase (GST) and aldehyde dehydrogenase (ALDH) enzymes. Polymorphisms of these enzymes may affect the pharmacokinetics of cyclophosphamide and thereby its toxicity and efficacy. The purpose of

Patent
14 Mar 2008
TL;DR: In this paper, a non-naturally occurring microbial biocatalyst including a microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (BDO) biosynthetic pathways was presented.
Abstract: The invention provides a non-naturally occurring microbial biocatalyst including a microbial organism having a 4-hydroxybutanoic acid (4-HB) biosynthetic pathway having at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, or α-ketoglutarate decarboxylase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce monomeric 4-hydroxybutanoic acid (4-HB). Also provided is a non-naturally occurring microbial biocatalyst including a microbial organism having 4-hydroxybutanoic acid (4-HB) and 1,4-butanediol (BDO) biosynthetic pathways, the pathways include at least one exogenous nucleic acid encoding 4-hydroxybutanoate dehydrogenase, succinyl-CoA synthetase, CoA-dependent succinic semialdehyde dehydrogenase, 4-hydroxybutyrate:CoA transferase, 4-butyrate kinase, phosphotransbutyrylase, α-ketoglutarate decarboxylase, aldehyde dehydrogenase, alcohol dehydrogenase or an aldehyde/alcohol dehydrogenase, wherein the exogenous nucleic acid is expressed in sufficient amounts to produce 1,4-butanediol (BDO). Additionally provided are methods for the production of 4-HB and BDO.

Journal ArticleDOI
TL;DR: It is illustrated that AldH is a potentially useful enzyme in converting 3-HPA to 3-HP with broad substrate specificity for various aliphatic and aromatic aldehydes.
Abstract: 3-Hydroxypropionaldehyde (3-HPA), an intermediary compound of glycerol metabolism in bacteria, serves as a precursor to 3-Hydroxypropionic acid (3-HP), a commercially valuable platform chemical. To achieve the effective conversion of 3-HPA to 3-HP, an aldH gene encoding an aldehyde dehydrogenase in Escherichia coli K-12 (AldH) was cloned, expressed, and characterized for its properties. The recombinant AldH exhibited broad substrate specificity for various aliphatic and aromatic aldehydes. AldH preferred NAD+ over NADP+ as a cofactor for the oxidation of most aliphatic aldehydes tested. Among the aldehydes used, the specific activity was highest (38.1 U mg−1 protein) for 3-HPA at pH 8.0 and 37 °C. The catalytic efficiency (kcat) and the specificity constant (kcat/Km) for 3-HPA in the presence of NAD+ were 28.5 s−1 and 58.6 × 103 M−1 s−1, respectively. The AldH activity was enhanced in the presence of disulfide reductants such as dithiothreitol (DTT) or 2-mercaptoethanol, while several metal ions, particularly Hg2+, Ag+, Cu2+, and Zn2+, inhibited AldH activity. This study illustrates that AldH is a potentially useful enzyme in converting 3-HPA to 3-HP.

Journal ArticleDOI
TL;DR: Object recognition and Morris water maze tests revealed that the onset of cognitive impairment correlated with the degeneration, which was further accelerated by APOE (apolipoprotein E) knock-out; therefore, the accumulation of toxic aldehydes is by itself critical in the progression of neurodegenerative disease, which could be suppressed by ALDH2.
Abstract: Oxidative stress may underlie age-dependent memory loss and cognitive decline. Toxic aldehydes, including 4-hydroxy-2-nonenal (HNE), an end product of lipid peroxides, are known to accumulate in the brain in neurodegenerative disease. We have previously shown that mitochondrial aldehyde dehydrogenase 2 (ALDH2) detoxifies HNE by oxidizing its aldehyde group. To investigate the role of such toxic aldehydes, we produced transgenic mice, which expressed a dominant-negative form of ALDH2 in the brain. The mice had decreased ability to detoxify HNE in their cortical neurons and accelerated accumulation of HNE in the brain. Consequently, their lifespan was shortened and age-dependent neurodegeneration and hyperphosphorylation of tau were observed. Object recognition and Morris water maze tests revealed that the onset of cognitive impairment correlated with the degeneration, which was further accelerated by APOE (apolipoprotein E) knock-out; therefore, the accumulation of toxic aldehydes is by itself critical in the progression of neurodegenerative disease, which could be suppressed by ALDH2.

Journal ArticleDOI
TL;DR: The significant interaction effects between markers in ADH and ALDH genes suggest possible epistatic roles between alcohol metabolic enzymes in the risk for AD.
Abstract: BACKGROUND: The genes coding for ethanol metabolism enzymes [alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH)] have been widely studied for their influence on the risk to develop alcohol dependence (AD). However, the relation between polymorphisms of these metabolism genes and AD in Caucasian subjects has not been clearly established. The present study examined evidence for the association of alcohol metabolism genes with AD in the Irish Affected Sib Pair Study of alcohol dependence. METHODS: We conducted a case-control association study with 575 independent subjects who met Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, AD diagnosis and 530 controls. A total of 77 single nucleotide polymorphisms (SNPs) in the seven ADH (ADH1-7) and two ALDH genes (ALDH1A1 and ALDH2) were genotyped using the Illumina GoldenGate protocols. Several statistical procedures were implemented to control for false discoveries. RESULTS: All markers with minor allele frequency greater than 0.01 were in Hardy-Weinberg equilibrium. Numerous SNPs in ADH genes showed association with AD, including one marker in the coding region of ADH1C (rs1693482 in exon6, Ile271Gln). Haplotypic association was observed in the ADH5 and ADH1C genes, and in a long haplotype block formed by the ADH1A and ADH1B loci. We detected two significant interactions between pairs of markers in intron 6 of ADH6 and intron 12 of ALDH2 (p = 5 x 10(-5)), and 5' of both ADH4 and ADH1A (p = 2 x 10(-4)). CONCLUSION: We found evidence for the association of several ADH genes with AD in a sample of Western European origin. The significant interaction effects between markers in ADH and ALDH genes suggest possible epistatic roles between alcohol metabolic enzymes in the risk for AD.

Journal ArticleDOI
TL;DR: The results suggest that ALDH-2 has an indirect antioxidative property independent of its thiol-moiety in disease states of cardiovascular oxidative stress.

Journal ArticleDOI
TL;DR: Test the hypothesis that the ALDH2 reaction is sufficient for GTN bioactivation and measured GTN-induced formation of cGMP by purified sGC in the presence of purified AlDH2 and used a Clark-type electrode to probe for nitric oxide (NO) formation, to explain the coupling of AL DH2-catalyzed GTN metabolism to sGC activation in vascular smooth muscle.

Journal ArticleDOI
TL;DR: Aldehyde dehydrogenases (ALDHs) play a central role in detoxification processes of aldehydes generated in plants when exposed to the stressed conditions.
Abstract: Aldehyde dehydrogenases (ALDHs) play a central role in detoxification processes of aldehydes generated in plants when exposed to the stressed conditions. In order to identify genes required for the stresses responses in the grass crop Zea mays, an ALDH (ZmALDH22A1) gene was isolated and characterized. ZmALDH22A1 belongs to the family ALDH22 that is currently known only in plants. The ZmALDH22A1 encodes a protein of 593 amino acids that shares high identity with the orthologs from Saccharum officinarum (95%), Oryza sativa (89%), Triticum aestivum (87%) and Arabidopsis thaliana (77%), respectively. Real-time PCR analysis indicates that ZmALDH22A1 is expressed differentially in different tissues. Various elevated levels of ZmALDH22A1 expression have been detected when the seedling roots exposed to abiotic stresses including dehydration, high salinity and abscisic acid (ABA). Tomato stable transformation of construct expressing the ZmALDH22A1 signal peptide fused with yellow fluorescent protein (YFP) driven by the CaMV35S-promoter reveals that the fusion protein is targeted to plastid. Transgenic tobacco plants overexpressing ZmALDH22A1 shows elevated stresses tolerance. Stresses tolerance in transgenic plants is accompanied by a reduction of malondialdehyde (MDA) derived from cellular lipid peroxidation.

Journal ArticleDOI
TL;DR: Enzyme kinetic studies show that oxidation of ω‐hydroxy‐VLCFAs occurs predominantly via the NAD+‐dependent route, and overall, the data demonstrate that in humans all enzymes are present for the com plete conversion of V LCFAs to their corresponding very‐long‐chain dicarboxylic acids.
Abstract: Very-long-chain fatty acids (VLCFAs) have long been known to be degraded exclusively in peroxisomes via beta-oxidation. A defect in peroxisomal beta-oxidation results in elevated levels of VLCFAs and is associated with the most frequent inherited disorder of the central nervous system white matter, X-linked adrenoleukodystrophy. Recently, we demonstrated that VLCFAs can also undergo omega-oxidation, which may provide an alternative route for the breakdown of VLCFAs. The omega-oxidation of VLCFA is initiated by CYP4F2 and CYP4F3B, which produce omega-hydroxy-VLCFAs. In this article, we characterized the enzymes involved in the formation of very-long-chain dicarboxylic acids from omega-hydroxy-VLCFAs. We demonstrate that very-long-chain dicarboxylic acids are produced via two independent pathways. The first is mediated by an as yet unidentified, microsomal NAD(+)-dependent alcohol dehydrogenase and fatty aldehyde dehydrogenase, which is encoded by the ALDH3A2 gene and is deficient in patients with Sjogren-Larsson syndrome. The second pathway involves the NADPH-dependent hydroxylation of omega-hydroxy-VLCFAs by CYP4F2, CYP4F3B, or CYP4F3A. Enzyme kinetic studies show that oxidation of omega-hydroxy-VLCFAs occurs predominantly via the NAD(+)-dependent route. Overall, our data demonstrate that in humans all enzymes are present for the complete conversion of VLCFAs to their corresponding very-long-chain dicarboxylic acids.

Journal ArticleDOI
TL;DR: The preliminary data on liver, stomach, and skin indicate that ALDH is polymorphic and several loci are concerned in the determination of these isozyme sets.
Abstract: Rapid and sensitive micromethods for the study of alcohol dehydrogenase and adehyde dehydrogenase isozymes in skin extracts, cultured fibroblasts and other organs are presented. Possibilities for the application of these techniques to the study of interindividual variations in response to alcohol are discussed. While fibroblasts cultured from a skin biopsy from one Japanese individual revealed a heterodimer (ADH2 2-1) of alcohol dehydrogenase, skin extract from another Japanese showed a homodimer (ADH2 2-2). Up to four isozyme sets for aldehyde dehydrogenase (ALDH) were detected in various human organs and at least three sets were found in skin and fibroblasts extracts. Our preliminary data on liver, stomach, and skin indicate that ALDH is polymorphic and several loci are concerned in the determination of these isozyme sets.

Journal ArticleDOI
TL;DR: It is found that alcohol consumption and polymorphisms in the CYP2E1, ADH1B and ALDH2 genes are important risk factors for esophageal squamous cell carcinoma and that there was a synergistic interaction among polymorphisms.
Abstract: Genetic polymorphisms in cytochrome P4502E1, alcohol and aldehyde dehydrogenases and the risk of esophageal squamous cell carcinoma in Gansu Chinese males

Journal ArticleDOI
TL;DR: Enzymatic analysis indicated that the affinity of BBD2 for betaine aldehyde was reasonable as other plant BADHs, but BBD1 showed extremely low affinity, and catalyzed the oxidation of omega-aminoaldehydes such as 4-aminobutyraldehyde and 3-aminopropionaldehyde as efficiently asBBD2.
Abstract: Betaine aldehyde dehydrogenase (BADH; EC 1.2.1.8) is an important enzyme that catalyzes the last step in the synthesis of glycine betaine, a compatible solute accumulated by many plants under various abiotic stresses. In barley (Hordeum vulgare L.), we reported previously the existence of two BADH genes (BBD1 and BBD2) and their corresponding proteins, peroxisomal BADH (BBD1) and cytosolic BADH (BBD2). To investigate their enzymatic properties, we expressed them in Escherichia coli and purified both proteins. Enzymatic analysis indicated that the affinity of BBD2 for betaine aldehyde was reasonable as other plant BADHs, but BBD1 showed extremely low affinity for betaine aldehyde with apparent K(m) of 18.9 microM and 19.9 mM, respectively. In addition, V(max)/K(m) with betaine aldehyde of BBD2 was about 2000-fold higher than that of BBD1, suggesting that BBD2 plays a main role in glycine betaine synthesis in barley plants. However, BBD1 catalyzed the oxidation of omega-aminoaldehydes such as 4-aminobutyraldehyde and 3-aminopropionaldehyde as efficiently as BBD2. We also found that both BBDs oxidized 4-N-trimethylaminobutyraldehyde and 3-N-trimethylaminopropionaldehyde.

Journal ArticleDOI
01 Apr 2008-Anaerobe
TL;DR: A bifunctional aldehyde/alcohol dehydrogenase gene (adhE) from Thermoanaerobacter ethanolicus JW200 was identified and cloned and it was shown that AdhE affected ethanol production.

Journal ArticleDOI
TL;DR: Genes identified in this study provide information on the potential mode of action of strong androgens in female fish and when used for screening of EDC's, these genes may also serve as sensitive markers of exposure to androgenic compounds.

Journal ArticleDOI
TL;DR: Differences in the activities of total ADH, ALDH and class I ADH isoenzyme between cancer liver tissues and healthy hepatocytes might be a factor in ethanol metabolism disorders, which can intensify carcinogenesis.
Abstract: Background/Aims Ethanol consumption is associated with an increased risk of esophageal cancer. The carcinogenic compound is acetaldehyde, the product of ethanol metabolism. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the main enzymes involved in ethanol metabolism, which leads to generation of acetaldehyde. In this study the activity of ADH isoenzymes and ALDH in esophageal cancer were compared with the activity in normal tissue. Methods For measurement of the activity of class I and II ADH isoenzymes and ALDH activity fluorimetric methods were employed. Total ADH activity and activity of class III and IV isoenzymes was measured by the photometric method. Samples were taken from 59 esophageal cancer patients (27 adenocarcinoma, 32 squamous cell cancer). Results The total activity of ADH and activity of class IV ADH were significantly higher in cancer cells than in healthy tissues. The other tested classes of ADH showed a tendency toward higher activity in cancer than in normal cells. Differences between the activity of enzymes of drinkers and non-drinkers in both cancer and healthy tissue were not significant. Conclusion Increased ADH IV activity may be a factor intensifying carcinogenesis, because of the increased ability to form acetaldehyde from ethanol.

Journal ArticleDOI
TL;DR: Polymorphisms of the ADH2 and ALDH2 genes are significantly associated with CRC risk in Chinese males and there are also significant gene-gene and gene-environment interactions between drinking and ADH 2 and AlDH2 polymorphisms regarding CRC risk.
Abstract: Polymorphisms of alcohol dehydrogenase 2 and aldehyde dehydrogenase 2 and colorectal cancer risk in Chinese males

Journal ArticleDOI
TL;DR: Changes in the activity of, especially, class IV ADH in the sera of patients with gastric cancer seems to be caused by release of the isoenzyme from cancer cells.
Abstract: Background Investigations have shown that alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are present in some cancer cells and can play role in carcinogenesis. In recent experiments we found elevated alcohol dehydrogenase class IV activity in gastric cancer cells. This suggests these changes may be reflected by enzyme activity in the serum. Aim In this work we measured the activity of alcohol dehydrogenase isoenzymes and aldehyde dehydrogenase in the sera of patients with gastric cancer matched on gender. Methods Serum samples were taken for routine biochemical investigation from 55 patients with gastric cancer, before treatment, and from 55 control subjects. Total ADH activity was measured photometrically and ALDH activity by a fluorimetric method. For measurement of the activity of class I isoenzymes we used a fluorimetric method, with class-specific fluorogenic substrates. The activity of class III and IV alcohol dehydrogenase was measured photometrically. Results The activity of the class IV ADH isoenzyme was significantly higher in the sera of patients with gastric cancer. The median activity of this isoenzyme in the total cancer group was approximately 47% higher (7.45 mU/l) than the control level (5.08 mU/l). For this reason total ADH activity was also significantly increased. The activities of other tested ADH isoenzymes and ALDH were unchanged. Conclusion Changes in the activity of, especially, class IV ADH in the sera of patients with gastric cancer seems to be caused by release of the isoenzyme from cancer cells.

Journal ArticleDOI
TL;DR: The results indicate that long-term caloric restriction induces sustained increases in the capacity for gluconeogenesis from glycerol, which is associated with a decrease in fasting blood Glycerol levels in CR animals.
Abstract: The influence of caloric restriction on hepatic glyceraldehyde- and glycerol-metabolizing enzyme activities of young and old mice were studied. Glycerol kinase and cytoplasmic glycerol-3-phosphate dehydrogenase activities were increased in both young and old CR (calorie-restricted) mice when compared with controls, whereas triokinase increased only in old CR mice. Aldehyde dehydrogenase and aldehyde reductase activities in both young and old CR mice were unchanged by caloric restriction. Mitochondrial glycerol-3-phosphate dehydrogenase showed a trend towards an increased activity in old CR mice, whereas a trend towards a decreased activity in alcohol dehydrogenase was observed in both young and old CR mice. Serum glycerol levels decreased in young and old CR mice. Therefore increases in glycerol kinase and glycerol-3-phosphate dehydrogenase were associated with a decrease in fasting blood glycerol levels in CR animals. A prominent role for triokinase in glyceraldehyde metabolism with CR was also observed. The results indicate that long-term caloric restriction induces sustained increases in the capacity for gluconeogenesis from glycerol.

Journal ArticleDOI
TL;DR: Results showed toxicity was well modelled by log P and electronic parameters ELUMO and partial charge of the carbonyl carbon and hydrophobicity and electronic descriptors were only significant in separate distinct models, suggesting that there were simultaneously occurring mechanisms that affected toxicity.
Abstract: Covalent binding of reactive electrophiles to cellular targets is a molecular interaction that has the potential to initiate severe adverse biological effects. Therefore, a measure for electrophilic reactivity with biological nucleophiles could serve as an important correlate to toxic effects such as hepatocyte death. To determine if electrophile reactivity correlates with rat hepatocyte cytotoxicity, the inherently electrophilic alpha,beta-unsaturated aldehydes were chosen for investigation. Reactivity was measured with simple assays that used glutathione, a soft nucleophile, and butylamine, a harder nucleophile, as models for protein thiol and amine nucleophilic sites, respectively. Despite their higher reactivity with thiols, a linear relationship was only observed between hepatocyte cytotoxicity and amine reactivity. Structure-activity relationships were also investigated for hepatocyte toxicity, and results showed toxicity was well modelled by log P and electronic parameters E(LUMO) and partial charge of the carbonyl carbon (C'(carb)). Hydrophobicity and electronic descriptors were only significant in separate distinct models, suggesting that there were simultaneously occurring mechanisms that affected toxicity. Log P was linked to the ease of oxidation by a microsomal aldehyde dehydrogenase enzyme, while the electronic descriptors and amine reactivity were linked to direct alkylation. Even with the presence of electrophile characteristics, alpha,beta-unsaturated aldehyde hepatocyte toxicity could not be predicted exclusively by electrophilic reactivity as oxidative metabolism was also a factor for toxicity.