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Revue Medicale de Liege May 2019Ethanol is rapidly and almost completely absorbed by the digestive tract, mainly in the small intestine. Alcohol is then metabolized mainly in the liver where it is...
Ethanol is rapidly and almost completely absorbed by the digestive tract, mainly in the small intestine. Alcohol is then metabolized mainly in the liver where it is converted into acetaldehyde. Two systems contribute to this metabolization, the predominant alcohol dehydrogenase pathway, and the pathway controlled by the microsomal ethanol oxidizing system (MEOS), which is inducible and is also involved in the metabolism of other drugs. Acetaldehyde is then metabolized to acetate, which largely leaves the liver to be converted into acetyl-CoA in other tissues. Alcohol is oxidized preferentially to other energetic substrates, leading, in turn, to a decrease in oxidation of lipids which are stored in adipose tissue.
Topics: Acetaldehyde; Alcohol Dehydrogenase; Ethanol; Humans; Liver; Oxidation-Reduction
PubMed: 31206264
DOI: No ID Found -
Biomedical Papers of the Medical... Mar 2016Alcohol variants such as ethanol and methanol are simple organic compounds widely used in foods, pharmaceuticals, chemical synthesis, etc. Both are becoming an emerging... (Review)
Review
BACKGROUND
Alcohol variants such as ethanol and methanol are simple organic compounds widely used in foods, pharmaceuticals, chemical synthesis, etc. Both are becoming an emerging health problem; abuse of ethanol containing beverages can lead to disparate health problems and methanol is highly toxic and unfit for consumption.
METHODS AND RESULTS
This review summarizes the basic knowledge about ethanol and methanol toxicity, the effect mechanism on the body, the current care of poisoned individuals and the implication of alcohols in the development of diseases. Alcohol related dementia, stroke, metabolic syndrome and hepatitis are discussed as well. Besides ethanol, methanol toxicity and its biodegradation pathways are addressed.
CONCLUSIONS
The impact of ethanol and methanol on the body is shown as case reports, along with a discussion on the possible implication of alcohol in Alzheimer's disease and antidotal therapy for methanol poisoning. The role of ethanol in cancer and degenerative disorders seems to be underestimated given the current knowledge. Treatment in case of poisoning is another issue that remains unresolved even though effective protocols and drugs exist.
Topics: Alcohol Dehydrogenase; Alcoholic Beverages; Alcoholism; Aldehyde Dehydrogenase; Antidotes; Ethanol; Humans; Methanol; Receptors, Cell Surface
PubMed: 26006090
DOI: 10.5507/bp.2015.023 -
Current Psychiatry Reports Mar 2019We review the search for genetic variants that affect the risk for alcohol dependence and alcohol consumption. (Review)
Review
PURPOSE OF REVIEW
We review the search for genetic variants that affect the risk for alcohol dependence and alcohol consumption.
RECENT FINDINGS
Variations in genes affecting alcohol metabolism (ADH1B, ALDH2) are protective against both alcohol dependence and excessive consumption, but different variants are found in different populations. There are different patterns of risk variants for alcohol dependence vs. consumption. Variants for alcohol dependence, but not consumption, are associated with risk for other psychiatric illnesses. ADH1B and ALDH2 strongly affect both consumption and dependence. Variations in many other genes affect both consumption and dependence-or one or the other of these traits-but individual effect sizes are small. Evidence for other specific genes that affect dependence is not yet strong. Most current knowledge derives from studies of European-ancestry populations, and large studies of carefully phenotyped subjects from different populations are needed to understand the genetic contributions to alcohol consumption and alcohol use disorders.
Topics: Alcohol Dehydrogenase; Alcohol Drinking; Alcoholism; Aldehyde Dehydrogenase, Mitochondrial; Humans
PubMed: 30852706
DOI: 10.1007/s11920-019-1008-1 -
Clinical and Experimental Medicine May 2017According to International Agency for Research on Cancer, ethanol and acetaldehyde belong to group 1 of human carcinogens. The accurate mechanism by which alcohol... (Review)
Review
According to International Agency for Research on Cancer, ethanol and acetaldehyde belong to group 1 of human carcinogens. The accurate mechanism by which alcohol consumption enhances carcinogenesis is still unexplained. Alcohol is oxidized primarily by alcohol dehydrogenase (ADH) to acetaldehyde, a substance capable of initiating carcinogenesis by forming adducts with proteins and DNA and causing mutations. Next, acetaldehyde is metabolized by aldehyde dehydrogenase (ALDH) to acetate. In tissues of many cancers, we can observe significantly higher activity of total alcohol dehydrogenase with any change in aldehyde dehydrogenase activity in comparison with healthy cells. Moreover, in malignant diseases of digestive system, significantly increased activity of ADH isoenzymes class I, III and IV was found. The gynecological, brain and renal cancers exhibit increased activity of class I ADH. ADH and ALDH can play also a crucial regulatory role in initiation and progression of malignant diseases by participation in retinoic acid synthesis and elimination of toxic acetaldehyde. Besides, changes of enzymes activities in tumor cells are reflected in serum of cancer patients, which create the possibilities of application ADH isoenzymes as cancer markers.
Topics: Alcohol Dehydrogenase; Aldehyde Dehydrogenase; Biomarkers; Humans; Neoplasms; Serum
PubMed: 26886278
DOI: 10.1007/s10238-016-0408-3 -
Chemico-biological Interactions Oct 2017Close to 80 years of research have brought MDR alcohol dehydrogenases (ADHs) from unknown molecular concepts to molecules known in exact detail regarding structural,...
Close to 80 years of research have brought MDR alcohol dehydrogenases (ADHs) from unknown molecular concepts to molecules known in exact detail regarding structural, functional and evolutionary properties. They can be traced backwards in at least six stages of development, to essentially the origin of cellular life, and have been monitored in a long series of biannual meetings on "Carbonyl Metabolism". In between each of these latest meetings, a roughly three-fold increase in known totals of MDR databank entries has been apparent, bringing the total now of known MDR-ADH entries to approaching half a million forms.
Topics: Alcohol Dehydrogenase; Animals; Biological Evolution; Databases, Factual; Fungal Proteins; Humans; Isoenzymes; Yeasts
PubMed: 27908777
DOI: 10.1016/j.cbi.2016.11.029 -
Biotechnology and Bioengineering May 2018Regulation of Bio-systems in a clean, simple, and efficient way is important for the design of smart bio-interfaces and bioelectronic devices. Light as a non-invasive...
Regulation of Bio-systems in a clean, simple, and efficient way is important for the design of smart bio-interfaces and bioelectronic devices. Light as a non-invasive mean to control the activity of a protein enables spatial and temporal control far superior to other chemical and physical methods. The ability to regulate the activity of a catalytic enzyme in a biofuel-cell reduces the waste of resources and energy and turns the fuel-cell into a smart and more efficient device for power generation. Here we present a microbial-fuel-cell based on a surface displayed, photo-switchable alcohol dehydrogenase. The enzyme was modified near the active site using non-canonical amino acids and a small photo-reactive molecule, which enables reversible control of enzymatic activity. Depending on the modification site, the enzyme exhibits reversible behavior upon irradiation with UV and visible light, in both biochemical, and electrochemical assays. The change observed in power output of a microbial fuel cell utilizing the modified enzyme was almost five-fold, between inactive and active states.
Topics: Alcohol Dehydrogenase; Bioelectric Energy Sources; Electricity; Enzymes, Immobilized; Light
PubMed: 29411858
DOI: 10.1002/bit.26555 -
Mini Reviews in Medicinal Chemistry 2019Methanol is the simplest alcohol. Compared to ethanol that is fully detoxified by metabolism. Methanol gets activated in toxic products by the enzymes, alcohol... (Review)
Review
Methanol is the simplest alcohol. Compared to ethanol that is fully detoxified by metabolism. Methanol gets activated in toxic products by the enzymes, alcohol dehydrogenase and aldehyde dehydrogenase. Paradoxically, the same enzymes convert ethanol to harmless acetic acid. This review is focused on a discussion and overview of the literature devoted to methanol toxicology and antidotal therapy. Regarding the antidotal therapy, three main approaches are presented in the text: 1) ethanol as a competitive inhibitor in alcohol dehydrogenase; 2) use of drugs like fomepizole inhibiting alcohol dehydrogenase; 3) tetrahydrofolic acid and its analogues reacting with the formate as a final product of methanol metabolism. All the types of antidotal therapies are described and how they protect from toxic sequelae of methanol is explained.
Topics: Alcohol Dehydrogenase; Antidotes; Enzyme Inhibitors; Humans; Methanol; Molecular Structure
PubMed: 30864518
DOI: 10.2174/1389557519666190312150407 -
Archiwum Medycyny Sadowej I Kryminologii 2016Alcohol dependence is both a medical and socioeconomic problem. The disease is multifactorial, i.e. its development is attributable to gene-gene and gene-environment... (Review)
Review
Alcohol dependence is both a medical and socioeconomic problem. The disease is multifactorial, i.e. its development is attributable to gene-gene and gene-environment interactions. Multi-centre studies investigating the genetic background of alcoholism stress the role of genes encoding enzymes of the ethanol decomposition pathway in the human body, particularly alcohol dehydrogenase (ADH), in the development of alcohol dependence. Among five classes of alcohol dehydrogenases, class I and IV isoenzymes have been found to be associated with alcohol dependence. Class IV is of particular interest due to its occurrence in the upper gastrointestinal tract, mainly in the stomach. No activity of the enzyme has been demonstrated in the liver. Single nucleotide polymorphism (SNP) of the gene encoding ADH class IV (ADH7) affects its ethanol-oxidizing activity in the gastric lumen, thereby influencing the first-pass metabolism (FPM) of the substance. The findings published by various research centres have demonstrated that specific SNP changes in the ADH7 gene are of different significance for the risk of alcohol dependence according to the population studied.
Topics: Alcohol Dehydrogenase; Alcohol Drinking; Aldehyde Dehydrogenase; Humans; Polymorphism, Single Nucleotide; Risk Factors
PubMed: 28453170
DOI: 10.5114/amsik.2016.66401 -
Trends in Microbiology Aug 2018Methylotrophy is a field of study dealing with microorganisms capable of utilization of compounds devoid of carbon-carbon bonds (C1 compounds). In this review, we... (Review)
Review
Methylotrophy is a field of study dealing with microorganisms capable of utilization of compounds devoid of carbon-carbon bonds (C1 compounds). In this review, we highlight several emerging trends in methylotrophy. First, we discuss the significance of the recent discovery of lanthanide-dependent alcohol dehydrogenases for understanding both the occurrence and the distribution of methylotrophy functions among bacteria, and then we discuss the newly appreciated role of lanthanides in biology. Next, we describe the detection of other methylotrophy pathways across novel bacterial taxa and insights into the evolution of methylotrophy. Further, data are presented on the occurrence and activity of aerobic methylotrophs in hypoxic and anoxic environments, questioning the prior assumptions on niche separation of aerobic and anaerobic methylotrophy. The concept of communal function in aerobic methane oxidation is also briefly discussed. Finally, we review recent research in engineering methylotrophs for biotechnological applications as well as recent progress in engineering synthetic methylotrophy.
Topics: Alcohol Dehydrogenase; Alcohol Oxidoreductases; Anaerobiosis; Bacteria; Genetic Engineering; Lanthanoid Series Elements; Methane; Oxidation-Reduction
PubMed: 29471983
DOI: 10.1016/j.tim.2018.01.011 -
Journal of Hepatology Jan 2017The susceptibility to developing alcohol dependence and significant alcohol-related liver injury is determined by a number of constitutional, environmental and genetic... (Review)
Review
The susceptibility to developing alcohol dependence and significant alcohol-related liver injury is determined by a number of constitutional, environmental and genetic factors, although the nature and level of interplay between them remains unclear. The familiality and heritability of alcohol dependence is well-documented but, to date, no strong candidate genes conferring increased risk have emerged, although variants in alcohol dehydrogenase and acetaldehyde dehydrogenase have been shown to confer protection, predominantly in individuals of East Asian ancestry. Population contamination with confounders such as drug co-dependence and psychiatric and physical co-morbidity may explain the essentially negative genome-wide association studies in this disorder. The familiality and hereditability of alcohol-related cirrhosis is not as well-documented but three strong candidate genes PNPLA3, TM6SF2 and MBOAT7, have been identified. The mechanisms by which variants in these genes confer risk and the nature of the functional interplay between them remains to be determined but, when elucidated, will undoubtedly increase our understanding of the pathophysiology of this disease. The way in which this genetic information could potentially inform patient management has yet to be determined and tested.
Topics: Alcohol Dehydrogenase; Alcoholism; Gene-Environment Interaction; Genetic Predisposition to Disease; Humans; Liver Diseases, Alcoholic; Polymorphism, Genetic; Protective Factors
PubMed: 27575312
DOI: 10.1016/j.jhep.2016.08.011