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| Acetaldehyde (IUPAC systematic name ethanal) is an organic chemical compound with the formula CH3CH=O, sometimes abbreviated as MeCH=O. It is a colorless liquid or gas, boiling near room temperature. It is one of the most important aldehydes, occurring widely in nature and being produced on a large scale in industry. Acetaldehyde occurs naturally in coffee, bread, and ripe fruit, and is produced by plants. It is also produced by the partial oxidation of ethanol by the liver enzyme alcohol dehydrogenase and is a contributing cause of hangover after alcohol consumption. Pathways of exposure include air, water, land, or groundwater, as well as drink and smoke. Consumption of disulfiram inhibits acetaldehyde dehydrogenase, the enzyme responsible for the metabolism of acetaldehyde, thereby causing it to build up in the body.
The International Agency for Research on Cancer (IARC) has listed acetaldehyde as a Group 1 carcinogen. Acetaldehyde is "one of the most frequently found air toxins with cancer risk greater than one in a million". |
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Read full article at Wikipedia
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| InChI=1S/C2H4O/c1-2-3/h2H,1H3 |
| IKHGUXGNUITLKF-UHFFFAOYSA-N |
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Mus musculus
(NCBI:txid10090)
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Source: BioModels - MODEL1507180067
See:
PubMed
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Saccharomyces cerevisiae
(NCBI:txid4932)
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Source: yeast.sf.net
See:
PubMed
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Escherichia coli
(NCBI:txid562)
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See:
PubMed
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Homo sapiens
(NCBI:txid9606)
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See:
DOI
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oxidising agent
A substance that removes electrons from another reactant in a redox reaction.
electron acceptor
A substance to which an electron may be transferred.
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Escherichia coli metabolite
Any bacterial metabolite produced during a metabolic reaction in Escherichia coli.
Saccharomyces cerevisiae metabolite
Any fungal metabolite produced during a metabolic reaction in Baker's yeast (Saccharomyces cerevisiae ).
human metabolite
Any mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
mouse metabolite
Any mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).
EC 3.5.1.4 (amidase) inhibitor
An EC 3.5.1.* (non-peptide linear amide C-N hydrolase) inhibitor that interferes with the action of amidase (EC 3.5.1.4).
carcinogenic agent
A role played by a chemical compound which is known to induce a process of carcinogenesis by corrupting normal cellular pathways, leading to the acquistion of tumoral capabilities.
mutagen
An agent that increases the frequency of mutations above the normal background level, usually by interacting directly with DNA and causing it damage, including base substitution.
teratogenic agent
A role played by a chemical compound in biological systems with adverse consequences in embryo developments, leading to birth defects, embryo death or altered development, growth retardation and functional defect.
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View more via ChEBI Ontology
Acetaldehyd
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NIST Chemistry WebBook
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Acetaldehyde
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KEGG COMPOUND
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ACETALDEHYDE
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PDBeChem
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acetaldehyde
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UniProt
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acetaldehydes
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ChEBI
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acetic aldehyde
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NIST Chemistry WebBook
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Azetaldehyd
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ChEBI
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Ethanal
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KEGG COMPOUND
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ethyl aldehyde
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NIST Chemistry WebBook
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505984
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Reaxys Registry Number
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Reaxys
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75-07-0
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CAS Registry Number
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NIST Chemistry WebBook
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75-07-0
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CAS Registry Number
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ChemIDplus
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779
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Gmelin Registry Number
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Gmelin
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Yao Z, Zhang C, Zhao J, Lu F, Bie X, Lu Z (2014)
Acetaldehyde detoxification using resting cells of recombinant Escherichia coli overexpressing acetaldehyde dehydrogenase.
Applied biochemistry and biotechnology 172, 2030-2040 [PubMed:24326678]
[show Abstract]
Acetaldehyde dehydrogenase (E.C. 1.2.1.10) plays a key role in the acetaldehyde detoxification. The recombinant Escherichia coli cells producing acetaldehyde dehydrogenase (ist-ALDH) were applied as whole-cell biocatalysts for biodegradation of acetaldehyde. Response surface methodology (RSM) was employed to enhance the production of recombinant ist-ALDH. Under the optimum culture conditions containing 20.68 h post-induction time, 126.75 mL medium volume and 3 % (v/v) inoculum level, the maximum ist-ALDH activity reached 496.65 ± 0.81 U/mL, resulting in 12.5-fold increment after optimization. Furthermore, the optimum temperature and pH for the catalytic activity of wet cells were 40 °C and pH 9.5, respectively. The biocatalytic activity was improved 80 % by permeabilizing the recombinant cells with 0.075 % (v/v) Triton X-100. When using 2 mmol/L NAD(+) as coenzyme, the permeabilized cells could catalyze 98 % of acetaldehyde within 15 min. The results indicated that the recombinant E. coli with high productivity of ist-ALDH might be highly efficient and easy-to-make biocatalysts for acetaldehyde detoxification. | Brooks PJ, Zakhari S (2014)
Acetaldehyde and the genome: beyond nuclear DNA adducts and carcinogenesis.
Environmental and molecular mutagenesis 55, 77-91 [PubMed:24282063]
[show Abstract]
The designation of acetaldehyde associated with the consumption of alcoholic beverages as "carcinogenic to humans" (Group 1) by the International Agency for Research on Cancer (IARC) has brought renewed attention to the biological effects of acetaldehyde, as the primary oxidative metabolite of alcohol. Therefore, the overall focus of this review is on acetaldehyde and its direct and indirect effects on the nuclear and mitochondrial genome. We first consider different acetaldehyde-DNA adducts, including a critical assessment of the evidence supporting a role for acetaldehyde-DNA adducts in alcohol related carcinogenesis, and consideration of additional data needed to make a conclusion. We also review recent data on the role of the Fanconi anemia DNA repair pathway in protecting against acetaldehyde genotoxicity and carcinogenicity, as well as teratogenicity. We also review evidence from the older literature that acetaldehyde may impact the genome indirectly, via the formation of adducts with proteins that are themselves critically involved in the maintenance of genetic and epigenetic stability. Finally, we note the lack of information regarding acetaldehyde effects on the mitochondrial genome, which is notable since aldehyde dehydrogenase 2 (ALDH2), the primary acetaldehyde metabolic enzyme, is located in the mitochondrion, and roughly 30% of East Asian individuals are deficient in ALDH2 activity due to a genetic variant in the ALDH2 gene. In summary, a comprehensive understanding of all of the mechanisms by which acetaldehyde impacts the function of the genome has implications not only for alcohol and cancer, but types of alcohol related pathologies as well. | Lui S, Jones RL, Robinson NJ, Greenwood SL, Aplin JD, Tower CL (2014)
Detrimental effects of ethanol and its metabolite acetaldehyde, on first trimester human placental cell turnover and function.
PloS one 9, e87328 [PubMed:24503565]
[show Abstract]
Fetal alcohol spectrum disorder (FASD) describes developmental issues from high maternal alcohol intake, which commonly results in fetal growth restriction and long term morbidity. We aimed to investigate the effect of alcohol and acetaldehyde, on the first trimester placenta, the period essential for normal fetal organogenesis. Normal invasion and establishment of the placenta during this time are essential for sustaining fetal viability to term. We hypothesise that alcohol (ethanol) and acetaldehyde have detrimental effects on cytotrophoblast invasion, turnover and placental function. Taurine is an important amino acid for neuronal and physiological development, and so, its uptake was assayed in cells and placental explants exposed to alcohol or acetaldehyde. First trimester villous explants and BeWo cells were treated with 0, 10, 20, 40 mM ethanol or 0, 10, 20, 40 µM acetaldehyde. The invasive capacity of SGHPL4, a first trimester extravillous cytotrophoblast cell line, was unaffected by ethanol or acetaldehyde (p>0.05; N = 6). The cells in-cycle were estimated using immunostaining for Ki67. Proliferating trophoblast cells treated with ethanol were decreased in both experiments (explants: 40% at 20 mM and 40 mM, p<0.05, N = 8-9) (cell line: 5% at 20 mM and 40 mM, p<0.05, N = 6). Acetaldehyde also reduced Ki67-positive cells in both experiments (explants at 40 µM p<0.05; N = 6) (cell line at 10 µM and 40 µM; p<0.05; N = 7). Only in the cell line at 20 µM acetaldehyde demonstrated increased apoptosis (p<0.05; N = 6). Alcohol inhibited taurine transport in BeWo cells at 10 mM and 40 mM (p<0.05; N = 6), and in placenta at 40 mM (p<0.05; N = 7). Acetaldehyde did not affect taurine transport in either model (P<0.05; N = 6). Interestingly, system A amino acid transport in placental explants was increased at 10 µM and 40 µM acetaldehyde exposure (p<0.05; N = 6). Our results demonstrate that exposure to both genotoxins may contribute to the pathogenesis of FASD by reducing placental growth. Alcohol also reduces the transport of taurine, which is vital for developmental neurogenesis. | Salaspuro M (2009)
Acetaldehyde as a common denominator and cumulative carcinogen in digestive tract cancers.
Scandinavian journal of gastroenterology 44, 912-925 [PubMed:19396661]
[show Abstract]
The key issue in cancer prevention is the identification of specific aetiologic factors. Acetaldehyde, the first metabolite of ethanol oxidation, is carcinogenic in animals. ADH and ALDH2 gene mutations provide an exceptional human model to estimate the long-term effects of acetaldehyde exposure in man. These models provide strong evidence for the local carcinogenic potential of acetaldehyde also in humans. Ethanol is metabolized to acetaldehyde by both mucosal and microbial enzymes. Many microbes produce acetaldehyde from ethanol, but their capacity to eliminate acetaldehyde is low, which leads to the accumulation of acetaldehyde in saliva during an alcohol challenge. Acetaldehyde is the most abundant carcinogen in tobacco smoke, and it readily dissolves into saliva during smoking. Fermented food and many alcoholic beverages can also contain significant amounts of acetaldehyde. Thus acetaldehyde, derived from mucosal or microbial oxidation of ethanol, tobacco smoke, and/or diet, appears to act as a cumulative carcinogen in the upper digestive tract of humans. The evidence strongly suggests the importance of world-wide screening of acetaldehyde and ethanol levels in many beverages and foodstuffs, as well as an urgent need for regulatory measures and consumer guidance. Screening of the risk groups with enhanced acetaldehyde exposure, e.g. people with ADH and ALDH2 gene polymorphisms and hypochlorhydric atrophic gastritis, should also be seriously considered. Most importantly, the GRAS (generally regarded as safe) status of acetaldehyde, which allows it to be used as a food additive, should be re-evaluated, and the classification of acetaldehyde as a carcinogen should be upgraded. | Melis M, Enrico P, Peana AT, Diana M (2007)
Acetaldehyde mediates alcohol activation of the mesolimbic dopamine system.
The European journal of neuroscience 26, 2824-2833 [PubMed:18001279]
[show Abstract]
Ethanol (EtOH), the main psychoactive ingredient of alcoholic drinks, is widely considered to be responsible for alcohol abuse and alcoholism through its positive motivational properties, which depend, at least partially, on the activation of the mesolimbic dopaminergic system. However, acetaldehyde (ACD), the first metabolite of EtOH, has been classically considered to be aversive and useful in the pharmacological therapy of alcoholics. Here we show that EtOH-derived ACD is necessary for EtOH-induced place preference, a pre-clinical test with high predictive validity for reward liability. We also found that ACD is essential for EtOH-increased microdialysate dopamine (DA) levels in the rat nucleus accumbens and that this effect is mimicked by intra-ventral tegmental area (VTA) ACD administration. Furthermore, in vitro, ACD enhances VTA DA neuronal firing through action on two ionic currents: reduction of the A-type K+ current and activation of the hyperpolarization-activated inward current. EtOH-stimulating properties on DA neurons are prevented by pharmacological blockade of local catalase, the main metabolic step for biotransformation of EtOH into ACD in the central nervous system. These results provide in-vivo and in-vitro evidence for a key role of ACD in the motivational properties of EtOH and its activation of the mesolimbic DA system. Additionally, these observations suggest that ACD, by increasing VTA DA neuronal activity, would oppose its well-known peripherally originating aversive properties. Careful consideration of these findings could help in devising new effective pharmacological therapies aimed at reducing EtOH intake in alcoholics. | Liu L, Li Y, Du G, Chen J (2006)
Redirection of the NADH oxidation pathway in Torulopsis glabrata leads to an enhanced pyruvate production.
Applied microbiology and biotechnology 72, 377-385 [PubMed:16404561]
[show Abstract]
This study aimed at increasing the pyruvate productivity of a multi-vitamin auxotrophic yeast Torulopsis glabrata by redirecting NADH oxidation from adenosine triphosphate (ATP)-production pathway (oxidative phosphorylation pathway) to non-ATP production pathway (fermentative pathway). Two respiratory-deficient mutants, RD-17 and RD-18, were screened and selected after ethidium bromide (EtBr) mutagenesis of the parent strain T. glabrata CCTCC M202019. Compared with the parent strain, cytochrome aa (3) and b in electron transfer chain (ETC) of RD-18 and cytochrome b in RD-17 were disrupted. As a consequence, the activities of key ETC enzymes of the mutant RD-18, including F(0)F(1)-ATP synthase, complex I, complex I + III, complex II + III, and complex IV, decreased by 22.2, 41.6, 53.1, 23.6, and 84.7%, respectively. With the deficiency of cytochromes in ETC, a large amount of excessive cytosolic NADH was accumulated, which hampered the further increase of the glycolytic flux. An exogenous electron acceptor, acetaldehyde, was added to the strain RD-18 culture to oxidize the excessive NADH. Compared with the parent strain, the concentration of pyruvate and the glucose consumption rate of strain RD-18 were increased by 26.5 and 17.6%, respectively, upon addition of 2.1 mM of acetaldehyde. The strategy for increasing the glycolytic flux in T. glabrata by redirecting the NADH oxidation pathway may provide an alternative approach to enhance the glycolytic flux in yeast. | Wang M, Yu N, Chen L, Villalta PW, Hochalter JB, Hecht SS (2006)
Identification of an acetaldehyde adduct in human liver DNA and quantitation as N2-ethyldeoxyguanosine.
Chemical research in toxicology 19, 319-324 [PubMed:16485909]
[show Abstract]
Acetaldehyde, an ubiquitous mutagen and carcinogen, could be involved in human cancer etiology. Because DNA adducts are important in carcinogenesis, we have used liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) to explore the presence in human liver DNA of the major acetaldehyde DNA adduct, N2-ethylidenedeoxyguanosine (1). DNA was isolated and enzymatically hydrolyzed in the presence of NaBH3CN, which quantitatively converts adduct 1 to N2-ethyldeoxyguanosine (N2-ethyl-dGuo, 2). [15N5]N2-Ethyl-dGuo was synthesized and used as an internal standard. Adduct 2 was enriched from the hydrolysate by solid phase extraction and analyzed by LC-ESI-MS/MS. Clear peaks were observed for adduct 2 in analyses of human liver DNA, calf thymus DNA, and rat liver DNA. These peaks were not observed, or were much smaller, when the NaBH3CN step was omitted. When the DNA was subjected to neutral thermal hydrolysis prior to NaBH3CN treatment, adduct 2 was not observed. Control experiments using [13C2]acetaldehyde demonstrated that adducts 1 and 2 were not formed as artifacts during DNA isolation and analysis. These results strongly indicate that adduct 1 is present in human liver DNA and demonstrate that it can be quantified as adduct 2. Levels of adduct 2 measured in 12 human liver samples were 534 +/- 245 fmol/micromol dGuo (mean +/- SD). The results of this study establish the presence of an acetaldehyde adduct in human liver DNA and suggest that it is a commonly occurring endogenous DNA adduct. | Lao Y, Hecht SS (2005)
Synthesis and properties of an acetaldehyde-derived oligonucleotide interstrand cross-link.
Chemical research in toxicology 18, 711-721 [PubMed:15833031]
[show Abstract]
Acetaldehyde (AA), occurring widely in the human environment, is a mutagen and carcinogen. AA can react with DNA to form AA-DNA adducts. Several types of adducts, including an interstrand cross-link 3-(2-deoxyribos-1-yl)-5,6,7,8-tetrahydro-8-(N2-deoxyguanosyl)-6-methylpyrimido[1,2-a]purine-10(3H)one (7), have been previously characterized by our laboratory. We hypothesize that cross-link 7 may be involved in determining the mutagenic and carcinogenic properties of AA. To address this question, the double-stranded oligonucleotide 13, bearing cross-link 7, was synthesized in a sequence appropriate for mutagenicity studies in human cells. Oligonucleotide 9, containing 2-fluoro-O6-(trimethylsilylethyl)deoxyinosine (dIno), was reacted with 4-amino-1,2-pentanediol, followed by treatment with NaIO4. The resulting oligonucleotide 11 containing the 1,N2-propano-deoxyguanosine (dGuo) 5 was incubated with the complementary oligonucleotide 12 to give the desired cross-link 13, which was characterized by negative-ion electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-Q-TOF-MS) and enzymatic hydrolysis to cross-link 7. The formation of cross-link 13 at 5'-CpG-3' was confirmed by incubation of 11 with [15N5]12 containing a 5'-Cp[15N5]G-3' sequence. The formation of cross-link 13 was reversible. Therefore, oligonucleotide 24 containing the irreversible analogue of cross-link 7, 1,3-bis(2'-deoxyguanos-N2-yl)butane, was synthesized for use as a control in the mutagenicity studies. Oligonucleotide 21 was reacted with 1,3-diaminobutane dihydrochloride, followed by incubation with the complementary oligonucleotide 23, to give 24. To determine the optimum distance and orientation for cross-link formation, six oligonucleotides, containing 5 at the i + 1, i + 2, and i + 3 or the i - 1, i - 2, and i - 3 positions relative to dGuo in the complementary strand, were 5'-end labeled with [gamma-32P]ATP, followed by incubation of each labeled oligonulceotide with its complementary strand and then analysis by denaturing polyacrylamide gel electrophoresis. Only the oligonucleotide containing 5'-Cp5-3' formed the cross-link with the complementary 5'-CpG-3' sequence. The results of this study confirm the structure of an AA-derived DNA cross-link, supply characterized cross-link-containing oligonucleotides for mutagenicity studies, and provide information on the optimum distance and orientation for cross-link formation. | Salaspuro V, Salaspuro M (2004)
Synergistic effect of alcohol drinking and smoking on in vivo acetaldehyde concentration in saliva.
International journal of cancer 111, 480-483 [PubMed:15239123]
[show Abstract]
Alcohol drinking and smoking are independent risk factors for upper digestive tract cancers. Furthermore, their combined use interacts in a multiplicative way on cancer risk. There is convincing evidence that acetaldehyde, the first metabolite of ethanol and a constituent of tobacco smoke, is a local carcinogen in humans. Therefore, we examined the combined effect of alcohol drinking and tobacco smoking on in vivo acetaldehyde concentration in saliva. Seven smokers and 6 nonsmokers participated in the study. First, to measure the effect of alcohol on salivary acetaldehyde, all volunteers ingested 0.8 g/kg body weight of ethanol and saliva samples were collected every 20 min for 160 min thereafter. After a 3-day washout period, smokers ingested again the same amount of ethanol and smoked one cigarette every 20 min and saliva samples were collected at 10 min intervals for 160 min. Acetaldehyde and ethanol concentrations were analyzed by headspace gas chromatograph. Firstly, smokers without concomitant smoking during ethanol challenge had 2 times higher in vivo salivary acetaldehyde concentrations than nonsmokers after ethanol ingestion (AUC 114.8 +/- 11.5 vs. 54.2 +/- 8.7 microM x hr, respectively; p = 0.002). Secondly, smokers with active smoking during ethanol challenge had 7 times higher in vivo salivary acetaldehyde levels than nonsmokers (AUC 369.5 +/- 12.2 vs. 54.2 +/- 8.7 microM x hr, respectively; p < 0.001). We conclude that this markedly increased exposure of upper digestive tract mucosa to carcinogenic salivary acetaldehyde of smoking and drinking subjects may explain the synergistic and multiplicative risk effect of alcohol drinking and tobacco smoking on upper gastrointestinal tract carcinogenesis. | Väkeväinen S, Tillonen J, Blom M, Jousimies-Somer H, Salaspuro M (2001)
Acetaldehyde production and other ADH-related characteristics of aerobic bacteria isolated from hypochlorhydric human stomach.
Alcoholism, clinical and experimental research 25, 421-426 [PubMed:11290854]
[show Abstract]
BackgroundAcetaldehyde is a known local carcinogen in the digestive tract in humans. Bacterial overgrowth in the hypochlorhydric stomach enhances production of acetaldehyde from ethanol in vivo after alcohol ingestion. Therefore, microbially produced acetaldehyde may be a potential risk factor for alcohol-related gastric and cardiac cancers. This study was aimed to investigate which bacterial species and/or groups are responsible for acetaldehyde formation in the hypochlorhydric human stomach and to characterize their alcohol dehydrogenase (ADH) enzymes.MethodsAfter 7 days of treatment with 30 mg of lansoprazole twice a day, a gastroscopy was performed on eight volunteers to obtain hypochlorhydric gastric juice. Samples were cultured and bacteria were isolated and identified; thereafter, their acetaldehyde production capacity was measured gas chromatographically by incubating intact bacterial suspensions with ethanol at 37 degrees C. Cytosolic ADH activities, Km values, and protein concentration were determined spectrophotometrically.ResultsAcetaldehyde production of the isolated bacterial strains (n = 51) varied from less than 1 to 13,690 nmol of acetaldehyde/10(9) colony-forming units/hr. ADH activity of the strains that produced more than 100 nmol of acetaldehyde/10(9) colony-forming units/hr (n = 23) varied from 3.9 to 1253 nmol of nicotinamide adenine dinucleotide per minute per milligram of protein, and Km values for ethanol ranged from 0.65 to 116 mM and from 0.5 to 3.1 M (high Km). There was a statistically significant correlation (r = 0.64, p < 0.001) between ADH activity and acetaldehyde production from ethanol in the tested strains. The most potent acetaldehyde producers were Neisseria and Rothia species and Streptococcus salivarius, whereas nearly all Stomatococcus, Staphylococcus, and other Streptococcus species had a very low capacity to produce acetaldehyde.ConclusionsThis study demonstrated that certain bacterial species or groups that originate from the oral cavity are responsible for the bulk of acetaldehyde production in the hypochlorhydric stomach. These findings provide new information with the respect to the local production of carcinogenic acetaldehyde in the upper digestive tract of achlorhydric human subjects. | Pahlman AK, Granath K, Ansell R, Hohmann S, Adler L (2001)
The yeast glycerol 3-phosphatases Gpp1p and Gpp2p are required for glycerol biosynthesis and differentially involved in the cellular responses to osmotic, anaerobic, and oxidative stress.
The Journal of biological chemistry 276, 3555-3563 [PubMed:11058591]
[show Abstract]
We have characterized the strongly homologous GPP1/RHR2 and GPP2/HOR2 genes, encoding isoforms of glycerol 3-phosphatase. Mutants lacking both GPP1 and GPP2 are devoid of glycerol 3-phosphatase activity and produce only a small amount of glycerol, confirming the essential role for this enzyme in glycerol biosynthesis. Overproduction of Gpp1p and Gpp2p did not significantly enhance glycerol production, indicating that glycerol phosphatase is not rate-limiting for glycerol production. Previous studies have shown that expression of both GPP1 and GPP2 is induced under hyperosmotic stress and that induction partially depends on the HOG (high osmolarity glycerol) pathway. We here show that expression of GPP1 is strongly decreased in strains having low protein kinase A activity, although it is still responsive to osmotic stress. The gpp1Delta/gpp2Delta double mutant is hypersensitive to high osmolarity, whereas the single mutants remain unaffected, indicating GPP1 and GPP2 substitute well for each other. Transfer to anaerobic conditions does not affect expression of GPP2, whereas GPP1 is transiently induced, and mutants lacking GPP1 show poor anaerobic growth. All gpp mutants show increased levels of glycerol 3-phosphate, which is especially pronounced when gpp1Delta and gpp1Delta/gpp2Delta mutants are transferred to anaerobic conditions. The addition of acetaldehyde, a strong oxidizer of NADH, leads to decreased glycerol 3-phosphate levels and restored anaerobic growth of the gpp1Delta/gpp2Delta mutant, indicating that the anaerobic accumulation of NADH causes glycerol 3-phosphate to reach growth-inhibiting levels. We also found the gpp1Delta/gpp2Delta mutant is hypersensitive to the superoxide anion generator, paraquat. Consistent with a role for glycerol 3-phosphatase in protection against oxidative stress, expression of GPP2 is induced in the presence of paraquat. This induction was only marginally affected by the general stress-response transcriptional factors Msn2p/4p or protein kinase A activity. We conclude that glycerol metabolism plays multiple roles in yeast adaptation to altered growth conditions, explaining the complex regulation of glycerol biosynthesis genes. | Wang M, McIntee EJ, Cheng G, Shi Y, Villalta PW, Hecht SS (2000)
Identification of DNA adducts of acetaldehyde.
Chemical research in toxicology 13, 1149-1157 [PubMed:11087437]
[show Abstract]
Acetaldehyde is a mutagen and carcinogen which occurs widely in the human environment, sometimes in considerable amounts, but little is known about its reactions with DNA. In this study, we identified three new types of stable acetaldehyde DNA adducts, including an interstrand cross-link. These were formed in addition to the previously characterized N(2)-ethylidenedeoxyguanosine. Acetaldehyde was allowed to react with calf thymus DNA or deoxyguanosine. The DNA was isolated and hydrolyzed enzymatically; in some cases, the DNA was first treated with NaBH(3)CN. Reaction mixtures were analyzed by HPLC, and adducts were isolated and characterized by UV, (1)H NMR, and MS. The major adduct was N(2)-ethylidenedeoxyguanosine (1), which was identified as N(2)-ethyldeoxyguanosine (7) after treatment of the DNA with NaBH(3)CN. The new acetaldehyde adducts were 3-(2-deoxyribos-1-yl)-5,6,7, 8-tetrahydro-8-hydroxy-6-methylpyrimido[1,2-a]purine-10(3H)one (9), 3-(2-deoxyribos-1-yl)-5,6,7,8-tetrahydro-8-(N(2)-deoxyguanosyl+ ++)- 6-methylpyrimido[1,2-a]purine-10(3H)one (12), and N(2)-(2, 6-dimethyl-1,3-dioxan-4-yl)deoxyguanosine (11). Adduct 9 has been previously identified in reactions of crotonaldehyde with DNA. However, the distribution of diastereomers was different in the acetaldehyde and crotonaldehyde reactions, indicating that the formation of 9 from acetaldehyde does not proceed through crotonaldehyde. Adduct 12 is an interstrand cross-link. Although previous evidence indicates the formation of cross-links in DNA reacted with acetaldehyde, this is the first reported structural characterization of such an adduct. This adduct is also found in crotonaldehyde-deoxyguanosine reactions, but in a diastereomeric ratio different than that observed here. A common intermediate, N(2)-(4-oxobut-2-yl)deoxyguanosine (6), is proposed to be involved in formation of adducts 9 and 12. Adduct 11 is produced ultimately from 3-hydroxybutanal, the major aldol condensation product of acetaldehyde. Levels of adducts 9, 11, and 12 were less than 10% of those of N(2)-ethylidenedeoxyguanosine (1) in reactions of acetaldehyde with DNA. As nucleosides, adducts 9, 11, and 12 were stable, whereas N(2)-ethylidenedeoxyguanosine (1) had a half-life of 5 min. These new stable adducts of acetaldehyde may be involved in determination of its mutagenic and carcinogenic properties. | Ansell R, Granath K, Hohmann S, Thevelein JM, Adler L (1997)
The two isoenzymes for yeast NAD+-dependent glycerol 3-phosphate dehydrogenase encoded by GPD1 and GPD2 have distinct roles in osmoadaptation and redox regulation.
The EMBO journal 16, 2179-2187 [PubMed:9171333]
[show Abstract]
The two homologous genes GPD1 and GPD2 encode the isoenzymes of NAD-dependent glycerol 3-phosphate dehydrogenase in the yeast Saccharomyces cerevisiae. Previous studies showed that GPD1 plays a role in osmoadaptation since its expression is induced by osmotic stress and gpd1 delta mutants are osmosensitive. Here we report that GPD2 has an entirely different physiological role. Expression of GPD2 is not affected by changes in external osmolarity, but is stimulated by anoxic conditions. Mutants lacking GPD2 show poor growth under anaerobic conditions. Mutants deleted for both GPD1 and GPD2 do not produce detectable glycerol, are highly osmosensitive and fail to grow under anoxic conditions. This growth inhibition, which is accompanied by a strong intracellular accumulation of NADH, is relieved by external addition of acetaldehyde, an effective oxidizer of NADH. Thus, glycerol formation is strictly required as a redox sink for excess cytosolic NADH during anaerobic metabolism. The anaerobic induction of GPD2 is independent of the HOG pathway which controls the osmotic induction of GPD1. Expression of GPD2 is also unaffected by ROX1 and ROX3, encoding putative regulators of hypoxic and stress-controlled gene expression. In addition, GPD2 is induced under aerobic conditions by the addition of bisulfite which causes NADH accumulation by inhibiting the final, reductive step in ethanol fermentation and this induction is reversed by addition of acetaldehyde. We conclude that expression of GPD2 is controlled by a novel, oxygen-independent, signalling pathway which is required to regulate metabolism under anoxic conditions. | Trudell JR, Ardies CM, Anderson WR (1990)
Cross-reactivity of antibodies raised against acetaldehyde adducts of protein with acetaldehyde adducts of phosphatidyl-ethanolamine: possible role in alcoholic cirrhosis.
Molecular pharmacology 38, 587-593 [PubMed:2233695]
[show Abstract]
This study measured the possible cross-reactivity of hapten-specific IgG antibodies purified from the sera of rabbits sensitized to an albumin-acetaldehyde conjugate [N-ethyl-rabbit serum albumin (N-ethyl-RSA)] with acetaldehyde-phosphatidylethanolamine adducts. The N-ethyl-RSA was coupled to an Affigel-10 column to affinity purify the IgG (anti-N-ethyl-RSA IgG). Dioleoyl-phosphatidylethanolamine (DOPE) was reacted with acetaldehyde to form a Schiff base, which was reduced to N-ethyl-DOPE, purified by high pressure liquid chromatography, and analyzed with direct chemical ionization mass spectrometry. Lamellar liposomes containing either 5% by weight N-ethyl-DOPE and 95% egg phosphatidylcholine or a mixture of 5% N-ethyl-DOPE, 71% DOPE, and 24% dioleoylphosphatidylcholine, as well as hexagonal phase micelles containing 5% N-ethyl-DOPE and 95% DOPE, were prepared by sonication. Anti-N-ethyl-RSA IgG was then incubated with each of these lipid mixtures for 30 min, a fluorescein-conjugated goat anti-rabbit IgG was added for an additional 30 min, and then binding of anti-N-ethyl-RSA IgG to N-ethyl-DOPE in the liposomes or micelles was measured by flow cytometry. Anti-N-ethyl-RSA IgG bound to N-ethyl-DOPE in both vesicles and hexagonal phase micelles, but the affinity was 16 times greater for the hapten in the hexagonal phase. This result demonstrates that physical presentation of the hapten can affect antibody recognition and that antibodies raised against N-ethyl-RSA can cross-react with acetaldehyde-phospholipid adducts. | Bannigan J, Burke P (1982)
Ethanol teratogenicity in mice: a light microscopic study.
Teratology 26, 247-254 [PubMed:7163973]
[show Abstract]
The objective of this study was to see what, if any, cellular changes occurred in the mouse embryo following a single injection of ethanol, a known teratogen in humans and animals, on day 9 of gestation. No changes were seen until 6 hours after injection, when many degenerating cells and necrotic fragments were seen in the neuroepithelium of the neural groove and of the neural tube. In addition, large clear vacuoles were seen in the cytoplasm of many cells and the pseudopodia at the luminal side of the neural groove appeared swollen. The cytoplasm of the latter also contained vacuoles. When tritiated thymidine was injected 5 hours after ethanol and 1 hour before sacrifice, many degenerating cells were labelled. In addition, many cells with labelled nuclei had abnormal vacuoles in the cytoplasm. Hence, it is likely that the toxicity of ethanol is exerted primarily on some component of the cytoplasm and not on DNA synthesis. Twelve hours after ethanol, the cytoplasmic vacuoles and swollen pseudopodia had disappeared, but dying cells were still evident. By 24 hours, the necrotic debris had been completely phagocytosed by healthy neuroepithelial cells. By 50 hours, the neuroepithelium had been cleared of cell debris, although many ethanol-treated embryos had open defects of the cranial neural tube. Treatment of pregnant mice with single doses of acetaldehyde, also an established teratogen in animals, did not produce any cellular changes. However, a single dose of acetaldehyde is rapidly metabolized by the mother, and would not be comparable to the small but continuous blood levels that a dose of ethanol would produce. Hence, we could not conclude with certainty that the cytotoxic effects of ethanol were exerted directly. | Gregoriou M, Brown PR (1979)
Inhibition of the aliphatic amidase from Pseudomonas aeruginosa by urea and related compounds.
European journal of biochemistry 96, 101-108 [PubMed:110589]
[show Abstract]
The time-dependent inhibition of amidase from Pseudomonas aeruginosa strain AI 3 by urea, hydroxyurea and cyanate displayed saturation kinetics fitting a model for the reaction sequence in which formation of a complex in a reversible step was followed by an irreversible step. Altered amidases from mutant strains AIU 1N and OUCH 4, selected for their resistance to inhibition of growth by urea and hydroxyurea respectively, had altered kinetic constants for inhibition indicating reduced binding capacity for the inhibitors. The substrate acetamide protected AI 3 amidase against inhibition by urea,.and altered Ki values for inhibition of the mutant amidases were paralleled by alterations in Km values for acetamide indicating that urea acted at the active site. Inhibition of AI 3 amidase involved the binding of one molecule of urea per molecule of enzyme. Urea inhibited amidase slowly regained activity at pH 7.2 through release of urea. | Freundt KJ (1970)
[Distribution and metabolism of acetaldehyde in blood].
Beitrage zur gerichtlichen Medizin 27, 368-372 [PubMed:5526694] | Jofre de Breyer IJ, Soehring K (1968)
[Effects of ethanol and acetaldehyde on serotonin metabolism in liver slices].
Naunyn-Schmiedebergs Archiv fur experimentelle Pathologie und Pharmakologie 260, 148-149 [PubMed:4239189] | Ammon HP, Estler CJ, Heim F (1967)
[The effect of acetaldehyde on coenzyme A activity and respiration of liver and brain mitochondria].
Biochemical pharmacology 16, 769-776 [PubMed:6036728] |
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