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Toxicological Sciences : An Official... Aug 2018Alcohol metabolism is a well-characterized biological process that is dominated by the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) families....
Alcohol metabolism is a well-characterized biological process that is dominated by the alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) families. Nonalcoholic steatohepatitis (NASH) is the advanced inflammatory stage of nonalcoholic fatty liver disease (NAFLD) and is known to alter the metabolism and disposition of numerous drugs. The purpose of this study was to investigate the alterations in alcohol metabolism processes in response to human NASH progression. Expression and function of ADHs, ALDHs, and catalase were examined in normal, steatosis, NASH (fatty) and NASH (not fatty) human liver samples. ALDH4A1 mRNA was significantly decreased in both NASH groups, while no significant changes were observed in the mRNA levels of other alcohol-related enzymes. The protein levels of ADH1A, ADH1B, and ADH4 were each decreased in the NASH groups, which was consistent with a decreased overall ADH activity. The protein level of ALDH2 was significantly increased in both NASH groups, while ALDH1A1 and ALDH1B1 were only decreased in NASH (fatty) samples. ALDH activity represented by oxidation of acetaldehyde was decreased in the NASH (fatty) group. The protein level of catalase was decreased in both NASH groups, though activity was unchanged. Furthermore, the significant accumulation of 4-hydroxynonenal protein adduct in NASH indicated significant oxidative stress and a potential reduction in ALDH activity. Collectively, ADH and ALDH expression and function are profoundly altered in the progression of NASH, which may have a notable impact on ADH- and ALDH-associated cellular metabolism processes and lead to significant alterations in drug metabolism mediated by these enzymes.
Topics: Alcohol Dehydrogenase; Aldehyde Dehydrogenase; Disease Progression; Ethanol; Humans; Isoenzymes; Liver; Non-alcoholic Fatty Liver Disease; Polymorphism, Single Nucleotide; RNA, Messenger
PubMed: 29718361
DOI: 10.1093/toxsci/kfy106 -
Molecules (Basel, Switzerland) Jun 2023Alcoholism is a worldwide health problem, and diseases caused by alcoholism are killing people every year. is a traditional Chinese medicine used to relieve hangovers....
Alcoholism is a worldwide health problem, and diseases caused by alcoholism are killing people every year. is a traditional Chinese medicine used to relieve hangovers. However, whether its bioactive components improve alcohol metabolism is not clear. In this study, ten new (amomumols A-J, -) and thirty-five known (-) compounds were isolated from the fruits of by an activity-guided separation. Ten novel compounds were identified as four sesquiterpenoids (-), three monoterpene derivatives (-), two neolignans (, ), and a novel norsesquiterpenoid () with a new C nor-bisabolane skeleton. Their structures were determined by the comprehensive analysis of high-resolution electrospray ionization mass spectrometry (HRESIMS), nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD) calculation. The effects of all isolated compounds on the activity of alcohol dehydrogenase were evaluated in vitro, and it was found that eight compounds (, , , , , and -) exhibited significant activation effects on the alcohol dehydrogenase at 50 μM.
Topics: Humans; Fruit; Amomum; Alcohol Dehydrogenase; Alcoholism; Monoterpenes
PubMed: 37375433
DOI: 10.3390/molecules28124878 -
Scientific Reports Jan 2022Acetogenic bacteria are capable of fermenting CO and carbon monoxide containing waste-gases into a range of platform chemicals and fuels. Despite major advances in...
Acetogenic bacteria are capable of fermenting CO and carbon monoxide containing waste-gases into a range of platform chemicals and fuels. Despite major advances in genetic engineering and improving these biocatalysts, several important physiological functions remain elusive. Among these is quorum sensing, a bacterial communication mechanism known to coordinate gene expression in response to cell population density. Two putative agr systems have been identified in the genome of Clostridium autoethanogenum suggesting bacterial communication via autoinducing signal molecules. Signal molecule-encoding agrD1 and agrD2 genes were targeted for in-frame deletion. During heterotrophic growth on fructose as a carbon and energy source, single deletions of either gene did not produce an observable phenotype. However, when both genes were simultaneously inactivated, final product concentrations in the double mutant shifted to a 1.5:1 ratio of ethanol:acetate, compared to a 0.2:1 ratio observed in the wild type control, making ethanol the dominant fermentation product. Moreover, CO re-assimilation was also notably reduced in both hetero- and autotrophic growth conditions. These findings were supported through comparative proteomics, which showed lower expression of carbon monoxide dehydrogenase, formate dehydrogenase A and hydrogenases in the ∆agrD1∆agrD2 double mutant, but higher levels of putative alcohol and aldehyde dehydrogenases and bacterial micro-compartment proteins. These findings suggest that Agr quorum sensing, and by inference, cell density play a role in carbon resource management and use of the Wood-Ljungdahl pathway as an electron sink.
Topics: Alcohol Dehydrogenase; Aldehyde Dehydrogenase; Aldehyde Oxidoreductases; Autotrophic Processes; Bacterial Proteins; Carbon Cycle; Carbon Dioxide; Carbon Monoxide; Clostridium; Energy Metabolism; Formate Dehydrogenases; Gene Expression Regulation, Bacterial; Gene Expression Regulation, Enzymologic; Heterotrophic Processes; Multienzyme Complexes; Mutation; Oxidoreductases; Quorum Sensing
PubMed: 35013405
DOI: 10.1038/s41598-021-03999-x -
Polish Journal of Pathology : Official... 2019This study was designed to examine the prevalence of Candida albicans alcohol dehydrogenase 1 (CaADH1) gene in oral dysplasia as well as oral squamous cell carcinoma...
This study was designed to examine the prevalence of Candida albicans alcohol dehydrogenase 1 (CaADH1) gene in oral dysplasia as well as oral squamous cell carcinoma (OSCC) with and without lymph node metastasis (LNM) using reverse transcription polymerase chain reaction (RT-PCR) in order to determine its role in initiation, propagation and metastasis of oral dysplasia and carcinoma. Formalin-fixed parafin-embedded specimens were grouped into four groups: 7 control, 16 oral dysplasia, 16 OSCC without LNM and 15 OSCC with LNM. All specimens were examined by periodic acid Schiff (PAS) stain to detect Candida hyphae, while CaADH1 gene was detected using RT-PCR. Candida hyphae were detected by PAS stain in one specimen of oral dysplasia group, 5 OSCC without LNM and 5 OSCC with LNM. CaADH1 gene was detected in 29 specimens (one case of sever dysplasia, 16 OSCC without LNM and 12 OSCC with LNM), with a highly statistically significant between the groups. CaADH1 gene is associated with OSCC with and without metastasis whereas in oral dysplasia it could not be estimated. Further studies with larger sample size are needed to confirm the role of CaADH1 in oral dysplasia and OSCC.
Topics: Alcohol Dehydrogenase; Candida albicans; Carcinoma, Squamous Cell; Fungal Proteins; Humans; Lymphatic Metastasis; Mouth Diseases; Mouth Neoplasms
PubMed: 31820865
DOI: 10.5114/pjp.2019.90398 -
Biotechnology Letters Aug 2022We describe a system that allows for biocatalyzed in vivo synthesis of α-hydroxy ketones from racemic epoxide starting material by in vivo co-expression of native and...
We describe a system that allows for biocatalyzed in vivo synthesis of α-hydroxy ketones from racemic epoxide starting material by in vivo co-expression of native and engineered epoxide hydrolase and alcohol dehydrogenases. The constructed expression system exploits the host cell metabolism for supply and regeneration of precious nicotinamide dinucleotide coenzyme. Racemic styrene oxide added to growth medium passively enters the cells and is hydrolyzed into (1R)-phenylethane-1,2-diol, which is subsequently oxidized to the acyloin 2-hydroxyacetophenone. Produced 2-hydroxyacetophenone escapes the cells via passive diffusion into the growth medium. Thus, co-expression of potato epoxide hydrolase and engineered alcohol dehydrogenase variants can be employed for robust and facile production of 2-hydroxyacetophenone from racemic styrene oxide.
Topics: Alcohol Dehydrogenase; Catalysis; Epoxide Hydrolases; Epoxy Compounds; Stereoisomerism
PubMed: 35731351
DOI: 10.1007/s10529-022-03271-w -
FEMS Yeast Research Mar 2021Methylotrophic yeasts are considered to use alcohol oxidases to assimilate methanol, different to bacteria which employ alcohol dehydrogenases with better energy...
Methylotrophic yeasts are considered to use alcohol oxidases to assimilate methanol, different to bacteria which employ alcohol dehydrogenases with better energy conservation. The yeast Komagataella phaffii carries two genes coding for alcohol oxidase, AOX1 and AOX2. The deletion of the AOX1 leads to the MutS phenotype and the deletion of AOX1 and AOX2 to the Mut- phenotype. The Mut- phenotype is commonly regarded as unable to utilize methanol. In contrast to the literature, we found that the Mut- strain can consume methanol. This ability was based on the promiscuous activity of alcohol dehydrogenase Adh2, an enzyme ubiquitously found in yeast and normally responsible for ethanol consumption and production. Using 13C labeled methanol as substrate we could show that to the largest part methanol is dissimilated to CO2 and a small part is incorporated into metabolites, the biomass, and the secreted recombinant protein. Overexpression of the ADH2 gene in K. phaffii Mut- increased both the specific methanol uptake rate and recombinant protein production, even though the strain was still unable to grow. These findings imply that thermodynamic and kinetic constraints of the dehydrogenase reaction facilitated the evolution towards alcohol oxidase-based methanol metabolism in yeast.
Topics: Alcohol Dehydrogenase; Alcohol Oxidoreductases; Fungal Proteins; Gene Expression Regulation, Fungal; Methanol; Promoter Regions, Genetic; Recombinant Proteins; Saccharomycetales
PubMed: 33599728
DOI: 10.1093/femsyr/foab009 -
EBioMedicine May 2024Alcohol consumption is associated with numerous negative social and health outcomes. These associations may be direct consequences of drinking, or they may reflect...
BACKGROUND
Alcohol consumption is associated with numerous negative social and health outcomes. These associations may be direct consequences of drinking, or they may reflect common genetic factors that influence both alcohol consumption and other outcomes.
METHODS
We performed exploratory phenome-wide association studies (PheWAS) of three of the best studied protective single nucleotide polymorphisms (SNPs) in genes encoding ethanol metabolising enzymes (ADH1B: rs1229984-T, rs2066702-A; ADH1C: rs698-T) using up to 1109 health outcomes across 28 phenotypic categories (e.g., substance-use, mental health, sleep, immune, cardiovascular, metabolic) from a diverse 23andMe cohort, including European (N ≤ 2,619,939), Latin American (N ≤ 446,646) and African American (N ≤ 146,776) populations to uncover new and perhaps unexpected associations. These SNPs have been consistently implicated by both candidate gene studies and genome-wide association studies of alcohol-related behaviours but have not been investigated in detail for other relevant phenotypes in a hypothesis-free approach in such a large cohort of multiple ancestries. To provide insight into potential causal effects of alcohol consumption on the outcomes significant in the PheWAS, we performed univariable two-sample and one-sample Mendelian randomisation (MR) analyses.
FINDINGS
The minor allele rs1229984-T, which is protective against alcohol behaviours, showed the highest number of PheWAS associations across the three cohorts (N = 232, European; N = 29, Latin American; N = 7, African American). rs1229984-T influenced multiple domains of health. We replicated associations with alcohol-related behaviours, mental and sleep conditions, and cardio-metabolic health. We also found associations with understudied traits related to neurological (migraines, epilepsy), immune (allergies), musculoskeletal (fibromyalgia), and reproductive health (preeclampsia). MR analyses identified evidence of causal effects of alcohol consumption on liability for 35 of these outcomes in the European cohort.
INTERPRETATION
Our work demonstrates that polymorphisms in genes encoding alcohol metabolising enzymes affect multiple domains of health beyond alcohol-related behaviours. Understanding the underlying mechanisms of these effects could have implications for treatments and preventative medicine.
FUNDING
MVJ, NCK, SBB, SSR and AAP were supported by T32IR5226 and 28IR-0070. SSR was also supported by NIDA DP1DA054394. NCK and RBC were also supported by R25MH081482. ASH was supported by funds from NIAAA K01AA030083. JLMO was supported by VA 1IK2CX002095. JLMO and JJMM were also supported by NIDA R21DA050160. JJMM was also supported by the Kavli Postdoctoral Award for Academic Diversity. EGA was supported by K01MH121659 from the NIMH/NIH, the Caroline Wiess Law Fund for Research in Molecular Medicine and the ARCO Foundation Young Teacher-Investigator Fund at Baylor College of Medicine. MSA was supported by the Instituto de Salud Carlos III and co-funded by the European Union Found: Fondo Social Europeo Plus (FSE+) (P19/01224, PI22/00464 and CP22/00128).
Topics: Humans; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Alcohol Drinking; Genome-Wide Association Study; Phenotype; Female; Cohort Studies; Male; Phenomics; Genetic Predisposition to Disease; Alcohol Dehydrogenase; Genotype; Alleles
PubMed: 38580523
DOI: 10.1016/j.ebiom.2024.105086 -
Scientific Reports Apr 2020The associations between genetic polymorphisms in ADH1B (rs1229984) and ALDH2 (rs671), alcohol consumption, the effect of a combination of the two polymorphisms, and...
The associations between genetic polymorphisms in ADH1B (rs1229984) and ALDH2 (rs671), alcohol consumption, the effect of a combination of the two polymorphisms, and breast cancer risk were studied in a population of East-Asian women. In this study, 623 breast cancer cases and 1845 controls, aged 40 or above, were included. The association between ALDH2 polymorphism and breast cancer risk was validated in 2143 breast cancer cases and 3977 controls. Alcohol consumption increased the risk of breast cancer regardless of ADH1B and ALDH2 genotypes. The rs671 polymorphism of ALDH2 was independently associated with increased breast cancer risk (OR = 1.27, 95% CI = 1.02-1.58 per increment of A). The ADH1B rs1229984 polymorphism, and combined effects of the rs671 and rs1229984 polymorphisms, did not reveal any significant association with breast cancer. Stratification by menopausal status revealed that rs671 gene polymorphisms were significantly associated with breast cancer only in postmenopausal women (OR = 1.45, 95% CI = 1.03-2.05 per increment of A). This is the first study to demonstrate an independent association between ALDH2 gene variants and breast cancer in Asian women. Further studies are warranted to further elucidate the etiology of breast cancer as it relates to alcohol consumption in Asian women.
Topics: Adult; Alcohol Dehydrogenase; Alcohol Drinking; Aldehyde Dehydrogenase, Mitochondrial; Asian People; Breast Neoplasms; Female; Genetic Predisposition to Disease; Genotype; Humans; Menopause; Middle Aged; Polymorphism, Single Nucleotide; Risk Factors
PubMed: 32300124
DOI: 10.1038/s41598-020-62361-9 -
Journal of Dairy Science Sep 2015Many human gastrointestinal facultative anaerobic and aerobic bacteria possess alcohol dehydrogenase (ADH) activity and are therefore capable of oxidizing ethanol to...
Many human gastrointestinal facultative anaerobic and aerobic bacteria possess alcohol dehydrogenase (ADH) activity and are therefore capable of oxidizing ethanol to acetaldehyde. However, the ADH activity of Lactococcus spp., except Lactococcus lactis ssp. lactis, has not been widely determined, though they play an important role as the starter for most cheesemaking technologies. Cheese is a functional food recognized as an aid to digestion. In the current study, the ADH activity of Lactococcus chungangensis CAU 28(T) and 11 reference strains from the genus Lactococcus was determined. Only 5 strains, 3 of dairy origin, L. lactis ssp. lactis KCTC 3769(T), L. lactis ssp. cremoris KCCM 40699(T), and Lactococcus raffinolactis DSM 20443(T), and 2 of nondairy origin, Lactococcus fujiensis NJ317(T) and Lactococcus chungangensis CAU 28(T) KCTC 13185(T), showed ADH activity and possessed the ADH gene. All these strains were capable of making cheese, but the highest level of ADH activity was found in L. chungangensis, with 45.9nmol/min per gram in tryptic soy broth and 65.8nmol/min per gram in cream cheese. The extent that consumption of cheese, following imbibing alcohol, reduced alcohol uptake was observed by following the level of alcohol in the serum of mice. The results show a potential novel benefit of cheese as a dairy functional food.
Topics: Alcohol Dehydrogenase; Animals; Cell Line, Tumor; Cell Survival; Cheese; Culture Media; Ethanol; Food Handling; L-Lactate Dehydrogenase; Lactococcus; Mice; Mice, Inbred ICR
PubMed: 26142864
DOI: 10.3168/jds.2015-9697 -
Chembiochem : a European Journal of... Jul 2021We present a one-pot cascade for the synthesis of phenylpropanolamines (PPAs) in high optical purities (er and dr up to >99.5 %) and analytical yields (up to 95 %)...
We present a one-pot cascade for the synthesis of phenylpropanolamines (PPAs) in high optical purities (er and dr up to >99.5 %) and analytical yields (up to 95 %) by using 1-phenylpropane-1,2-diols as key intermediates. This bioamination entails the combination of an alcohol dehydrogenase (ADH), an ω-transaminase (ωTA) and an alanine dehydrogenase to create a redox-neutral network, which harnesses the exquisite and complementary regio- and stereo-selectivities of the selected ADHs and ωTAs. The requisite 1-phenylpropane-1,2-diol intermediates were obtained from trans- or cis-β-methylstyrene by combining a styrene monooxygenase with epoxide hydrolases. Furthermore, in selected cases, the envisioned cascade enabled to obtain the structural isomer (1S,2R)-1-amino-1-phenylpropan-2-ol in high optical purity (er and dr >99.5 %). This is the first report on an enzymatic method that enables to obtain all of the four possible PPA stereoisomers in great enantio- and diastereo-selectivity.
Topics: Alanine Dehydrogenase; Alcohol Dehydrogenase; Alcohols; Biocatalysis; Oxidation-Reduction; Phenylpropanolamine; Stereoisomerism; Styrenes; Transaminases
PubMed: 33880862
DOI: 10.1002/cbic.202100123