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Clinics in Liver Disease Nov 2012This article describes the pathways and factors that modulate blood alcohol levels and metabolism and describes how the body disposes of alcohol. The various factors... (Review)
Review
This article describes the pathways and factors that modulate blood alcohol levels and metabolism and describes how the body disposes of alcohol. The various factors that play a role in the distribution of alcohol in the body, influence the absorption of alcohol, and contribute to first-pass metabolism of alcohol are described. Most alcohol is oxidized in the liver, and general principles and overall mechanisms for alcohol oxidation are summarized. The kinetics of alcohol elimination in-vivo and the various genetic and environmental factors that can modify the rate of alcohol metabolism are discussed.
Topics: Absorption; Acetaldehyde; Alcohol Dehydrogenase; Alcoholism; Cytochrome P-450 CYP2E1; Electron Transport; Ethanol; Female; Food-Drug Interactions; Humans; Kinetics; Liver; Male; NAD; Oxidation-Reduction; Tissue Distribution
PubMed: 23101976
DOI: 10.1016/j.cld.2012.08.002 -
Drug Metabolism Reviews Nov 2019This article summarizes recent experimental and epidemiological data on the toxic and beneficial effects of ethanol and its metabolites (acetaldehyde), and focuses on... (Review)
Review
This article summarizes recent experimental and epidemiological data on the toxic and beneficial effects of ethanol and its metabolites (acetaldehyde), and focuses on their immunomodulatory effects. The section dealing with the toxic effects of alcohol focuses on its chronic toxicity (liver disorders, carcinogenic effects, cardiovascular disorders, neuropsychic disorders, addiction and withdrawal syndrome, hematologic disorders, reprotoxicity, osteoporosis) although acute toxicity is considered. The role of oxidative metabolism of ethanol by alcohol dehydrogenase, cytochrome P450 2E1, and aldehyde dehydrogenase, as well as the impact of genetic polymorphism in its physiopathology are also highlighted. The section dealing with the beneficial effects of low to moderate alcohol consumption (on cardiovascular system, diabetes, the nervous system and sensory organs, autoimmune diseases, and rheumatology) highlights the importance of anti-inflammatory and immunomodulatory effects in these observations. This knowledge, enriched by a focus on the immunomodulatory effects of ethanol and its metabolites, in particular on the NLRP3 inflammasome pathway, might facilitate the development of treatments that can reduce ethanol's harmful effects or accentuate its beneficial effects.
Topics: Alcohol Drinking; Alcoholism; Animals; Ethanol; Humans; Immunologic Factors
PubMed: 31646907
DOI: 10.1080/03602532.2019.1679169 -
Nutrients Sep 2021Approximately 4% of cancers worldwide are caused by alcohol consumption. Drinking alcohol increases the risk of several cancer types, including cancers of the upper... (Review)
Review
Approximately 4% of cancers worldwide are caused by alcohol consumption. Drinking alcohol increases the risk of several cancer types, including cancers of the upper aerodigestive tract, liver, colorectum, and breast. In this review, we summarise the epidemiological evidence on alcohol and cancer risk and the mechanistic evidence of alcohol-mediated carcinogenesis. There are several mechanistic pathways by which the consumption of alcohol, as ethanol, is known to cause cancer, though some are still not fully understood. Ethanol's metabolite acetaldehyde can cause DNA damage and block DNA synthesis and repair, whilst both ethanol and acetaldehyde can disrupt DNA methylation. Ethanol can also induce inflammation and oxidative stress leading to lipid peroxidation and further DNA damage. One-carbon metabolism and folate levels are also impaired by ethanol. Other known mechanisms are discussed. Further understanding of the carcinogenic properties of alcohol and its metabolites will inform future research, but there is already a need for comprehensive alcohol control and cancer prevention strategies to reduce the burden of cancer attributable to alcohol.
Topics: Acetaldehyde; Alcohol Drinking; Alcohol-Induced Disorders; Carcinogenesis; DNA Damage; DNA Methylation; Ethanol; Humans; Neoplasms
PubMed: 34579050
DOI: 10.3390/nu13093173 -
Journal of Lipid Research Apr 2020Alcoholic liver disease (ALD) is the most prevalent type of chronic liver disease with significant morbidity and mortality worldwide. ALD begins with simple hepatic... (Review)
Review
Alcoholic liver disease (ALD) is the most prevalent type of chronic liver disease with significant morbidity and mortality worldwide. ALD begins with simple hepatic steatosis and progresses to alcoholic steatohepatitis, fibrosis, and cirrhosis. The severity of hepatic steatosis is highly associated with the development of later stages of ALD. This review explores the disturbances of alcohol-induced hepatic lipid metabolism through altered hepatic lipid uptake, de novo lipid synthesis, fatty acid oxidation, hepatic lipid export, and lipid droplet formation and catabolism. In addition, we review emerging data on the contributions of genetics and bioactive lipid metabolism in alcohol-induced hepatic lipid accumulation.
Topics: Animals; Ethanol; Humans; Lipid Metabolism; Lipogenesis; Liver
PubMed: 32029510
DOI: 10.1194/jlr.R119000547 -
International Journal of Molecular... May 2021Alcoholic liver disease (ALD) is a globally prevalent chronic liver disease caused by chronic or binge consumption of alcohol. The liver is the major organ that... (Review)
Review
Alcoholic liver disease (ALD) is a globally prevalent chronic liver disease caused by chronic or binge consumption of alcohol. The liver is the major organ that metabolizes alcohol; therefore, it is particularly sensitive to alcohol intake. Metabolites and byproducts generated during alcohol metabolism cause liver damage, leading to ALD via several mechanisms, such as impairing lipid metabolism, intensifying inflammatory reactions, and inducing fibrosis. Despite the severity of ALD, the development of novel treatments has been hampered by the lack of animal models that fully mimic human ALD. To overcome the current limitations of ALD studies and therapy development, it is necessary to understand the molecular mechanisms underlying alcohol-induced liver injury. Hence, to provide insights into the progression of ALD, this review examines previous studies conducted on alcohol metabolism in the liver. There is a particular focus on the occurrence of ALD caused by hepatotoxicity originating from alcohol metabolism.
Topics: Animals; Disease Susceptibility; Ethanol; Hepatocytes; Humans; Immune System; Immunomodulation; Inactivation, Metabolic; Lipid Metabolism; Liver; Liver Cirrhosis; Liver Diseases, Alcoholic; Liver Neoplasms; Metabolic Networks and Pathways; Oxidation-Reduction; Reactive Oxygen Species; Sensitivity and Specificity
PubMed: 34071962
DOI: 10.3390/ijms22115717 -
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 -
Journal of Translational Medicine May 2023Alcoholism is a widespread and damaging behaviour of people throughout the world. Long-term alcohol consumption has resulted in alcoholic liver disease (ALD) being the... (Review)
Review
Alcoholism is a widespread and damaging behaviour of people throughout the world. Long-term alcohol consumption has resulted in alcoholic liver disease (ALD) being the leading cause of chronic liver disease. Many metabolic enzymes, including alcohol dehydrogenases such as ADH, CYP2E1, and CATacetaldehyde dehydrogenases ALDHsand nonoxidative metabolizing enzymes such as SULT, UGT, and FAEES, are involved in the metabolism of ethanol, the main component in alcoholic beverages. Ethanol consumption changes the functional or expression profiles of various regulatory factors, such as kinases, transcription factors, and microRNAs. Therefore, the underlying mechanisms of ALD are complex, involving inflammation, mitochondrial damage, endoplasmic reticulum stress, nitrification, and oxidative stress. Moreover, recent evidence has demonstrated that the gut-liver axis plays a critical role in ALD pathogenesis. For example, ethanol damages the intestinal barrier, resulting in the release of endotoxins and alterations in intestinal flora content and bile acid metabolism. However, ALD therapies show low effectiveness. Therefore, this review summarizes ethanol metabolism pathways and highly influential pathogenic mechanisms and regulatory factors involved in ALD pathology with the aim of new therapeutic insights.
Topics: Humans; Liver Diseases, Alcoholic; Liver; Ethanol; Alcoholism; Alcohol Dehydrogenase
PubMed: 37143126
DOI: 10.1186/s12967-023-04166-8 -
FEMS Yeast Research Sep 2014The origin of modern fruits brought to microbial communities an abundant source of rich food based on simple sugars. Yeasts, especially Saccharomyces cerevisiae, usually... (Review)
Review
The origin of modern fruits brought to microbial communities an abundant source of rich food based on simple sugars. Yeasts, especially Saccharomyces cerevisiae, usually become the predominant group in these niches. One of the most prominent and unique features and likely a winning trait of these yeasts is their ability to rapidly convert sugars to ethanol at both anaerobic and aerobic conditions. Why, when, and how did yeasts remodel their carbon metabolism to be able to accumulate ethanol under aerobic conditions and at the expense of decreasing biomass production? We hereby review the recent data on the carbon metabolism in Saccharomycetaceae species and attempt to reconstruct the ancient environment, which could promote the evolution of alcoholic fermentation. We speculate that the first step toward the so-called fermentative lifestyle was the exploration of anaerobic niches resulting in an increased metabolic capacity to degrade sugar to ethanol. The strengthened glycolytic flow had in parallel a beneficial effect on the microbial competition outcome and later evolved as a "new" tool promoting the yeast competition ability under aerobic conditions. The basic aerobic alcoholic fermentation ability was subsequently "upgraded" in several lineages by evolving additional regulatory steps, such as glucose repression in the S. cerevisiae clade, to achieve a more precise metabolic control.
Topics: Biological Evolution; Ethanol; Fermentation; Glycolysis; Saccharomyces cerevisiae; Yeasts
PubMed: 24824836
DOI: 10.1111/1567-1364.12161 -
Nutrients Mar 2020The effects of alcohol on cardiovascular health are heterogeneous and vary according toconsumption dose and pattern. These effects have classically been described as... (Review)
Review
The effects of alcohol on cardiovascular health are heterogeneous and vary according toconsumption dose and pattern. These effects have classically been described as having a J-shapedcurve, in which low-to-moderate consumption is associated with less risk than lifetime abstention,and heavy drinkers show the highest risk. Nonetheless, the beneficial effects of alcohol have beenquestioned due to the difficulties in establishing a safe drinking threshold. This review focuses onthe association between alcohol consumption and cardiovascular risk factors and the underlyingmechanisms of damage, with review of the literature from the last 10 years.
Topics: Alcohol Drinking; Cardiovascular Diseases; Cardiovascular System; Diabetes Mellitus, Type 2; Ethanol; Humans; Inflammation; Oxidative Stress; Risk Factors
PubMed: 32230720
DOI: 10.3390/nu12040912 -
Nutrients Mar 2023Chronic alcohol use has been attributed to the development of malnutrition. This is in part due to the inhibitory effect of ethanol on the absorption of vital nutrients,... (Review)
Review
Chronic alcohol use has been attributed to the development of malnutrition. This is in part due to the inhibitory effect of ethanol on the absorption of vital nutrients, including glucose, amino acids, lipids, water, vitamins, and minerals within the small intestine. Recent advances in research, along with new cutting-edge technologies, have advanced our understanding of the mechanism of ethanol's effect on intestinal nutrient absorption at the brush border membrane (BBM) of the small intestine. However, further studies are needed to delineate how ethanol consumption could have an impact on altered nutrient absorption under various disease conditions. Current research has elucidated the relationship of alcohol consumption on glucose, glutamine, vitamins B1 (thiamine), B2 (riboflavin), B9 (folate), C (ascorbic acid), selenium, iron, and zinc absorption within the small intestine. We conducted systematic computerized searches in PubMed using the following keywords: (1) "Alcohol effects on nutrient transport"; (2) "Alcohol mediated malabsorption of nutrients"; (3) "Alcohol effects on small intestinal nutrient transport"; and (4) "Alcohol mediated malabsorption of nutrients in small intestine". We included the relevant studies in this review. The main objective of this review is to marshal and analyze previously published research articles and discuss, in-depth, the understanding of ethanol's effect in modulating absorption of vital macro and micronutrients in health and disease conditions. This could ultimately provide great insights in the development of new therapeutic strategies to combat malnutrition associated with alcohol consumption.
Topics: Humans; Intestinal Absorption; Alcohol Drinking; Ethanol; Nutrients; Malnutrition; Vitamins; Glucose
PubMed: 37049411
DOI: 10.3390/nu15071571