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Alcohol metabolism and epigenetics changes.

Zakhari S - Alcohol Res (2013)

Bottom Line: For example, the activities of enzymes involved in epigenetic modifications such as DNA and histone methylation and histone acetylation, are influenced by the levels of metabolites such as nicotinamide adenine dinucleotide (NAD), adenosine triphosphate (ATP), and S-adenosylmethionine (SAM).Chronic alcohol consumption leads to significant reductions in SAM levels, thereby contributing to DNA hypomethylation.Similarly, ethanol metabolism alters the ratio of NAD+ to reduced NAD (NADH) and promotes the formation of reactive oxygen species and acetate, all of which impact epigenetic regulatory mechanisms.

View Article: PubMed Central - PubMed

Affiliation: Division of Metabolism and Health Effects, National Institute on Alcohol Abuse and Alcoholism, USA.

ABSTRACT
Metabolites, including those generated during ethanol metabolism, can impact disease states by binding to transcription factors and/or modifying chromatin structure, thereby altering gene expression patterns. For example, the activities of enzymes involved in epigenetic modifications such as DNA and histone methylation and histone acetylation, are influenced by the levels of metabolites such as nicotinamide adenine dinucleotide (NAD), adenosine triphosphate (ATP), and S-adenosylmethionine (SAM). Chronic alcohol consumption leads to significant reductions in SAM levels, thereby contributing to DNA hypomethylation. Similarly, ethanol metabolism alters the ratio of NAD+ to reduced NAD (NADH) and promotes the formation of reactive oxygen species and acetate, all of which impact epigenetic regulatory mechanisms. In addition to altered carbohydrate metabolism, induction of cell death, and changes in mitochondrial permeability transition, these metabolism-related changes can lead to modulation of epigenetic regulation of gene expression. Understanding the nature of these epigenetic changes will help researchers design novel medications to treat or at least ameliorate alcohol-induced organ damage.

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Related in: MedlinePlus

Schematic representation of DNA methylation, which converts cytosine to 5′methyl-cytosine via the actions of DNA methyltransferase (DNMT). DNA methylation typically occurs at cytosines that are followed by a guanine (i.e., CpG motifs).NOTES: SAM = S-adenosylmethionine; SAH = S-adenosylhomocysteine.
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f1-arcr-35-1-6: Schematic representation of DNA methylation, which converts cytosine to 5′methyl-cytosine via the actions of DNA methyltransferase (DNMT). DNA methylation typically occurs at cytosines that are followed by a guanine (i.e., CpG motifs).NOTES: SAM = S-adenosylmethionine; SAH = S-adenosylhomocysteine.

Mentions: The cytosine moiety of cytosine–guanine (CpG) dinucleotides in mammalian DNA can be methylated at carbon 5 to form 5′ methyl-cytosine (figure 1). The methyl group for this chemical modification of the DNA is donated by SAM. This reaction is catalyzed by a family of DNMTs. Of these, DNMT3A and 3B primarily perform de novo methyl transfer, whereas DNMT1 mainly acts as maintenance DNMT with greater affinity for partially methylated (i.e., hemi-methylated) DNA. Methylation of cytosine in CpG-rich regions (i.e., CpG islands) located in or near gene promoters results in gene silencing (Ulrey et al. 2005).


Alcohol metabolism and epigenetics changes.

Zakhari S - Alcohol Res (2013)

Schematic representation of DNA methylation, which converts cytosine to 5′methyl-cytosine via the actions of DNA methyltransferase (DNMT). DNA methylation typically occurs at cytosines that are followed by a guanine (i.e., CpG motifs).NOTES: SAM = S-adenosylmethionine; SAH = S-adenosylhomocysteine.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3860421&req=5

f1-arcr-35-1-6: Schematic representation of DNA methylation, which converts cytosine to 5′methyl-cytosine via the actions of DNA methyltransferase (DNMT). DNA methylation typically occurs at cytosines that are followed by a guanine (i.e., CpG motifs).NOTES: SAM = S-adenosylmethionine; SAH = S-adenosylhomocysteine.
Mentions: The cytosine moiety of cytosine–guanine (CpG) dinucleotides in mammalian DNA can be methylated at carbon 5 to form 5′ methyl-cytosine (figure 1). The methyl group for this chemical modification of the DNA is donated by SAM. This reaction is catalyzed by a family of DNMTs. Of these, DNMT3A and 3B primarily perform de novo methyl transfer, whereas DNMT1 mainly acts as maintenance DNMT with greater affinity for partially methylated (i.e., hemi-methylated) DNA. Methylation of cytosine in CpG-rich regions (i.e., CpG islands) located in or near gene promoters results in gene silencing (Ulrey et al. 2005).

Bottom Line: For example, the activities of enzymes involved in epigenetic modifications such as DNA and histone methylation and histone acetylation, are influenced by the levels of metabolites such as nicotinamide adenine dinucleotide (NAD), adenosine triphosphate (ATP), and S-adenosylmethionine (SAM).Chronic alcohol consumption leads to significant reductions in SAM levels, thereby contributing to DNA hypomethylation.Similarly, ethanol metabolism alters the ratio of NAD+ to reduced NAD (NADH) and promotes the formation of reactive oxygen species and acetate, all of which impact epigenetic regulatory mechanisms.

View Article: PubMed Central - PubMed

Affiliation: Division of Metabolism and Health Effects, National Institute on Alcohol Abuse and Alcoholism, USA.

ABSTRACT
Metabolites, including those generated during ethanol metabolism, can impact disease states by binding to transcription factors and/or modifying chromatin structure, thereby altering gene expression patterns. For example, the activities of enzymes involved in epigenetic modifications such as DNA and histone methylation and histone acetylation, are influenced by the levels of metabolites such as nicotinamide adenine dinucleotide (NAD), adenosine triphosphate (ATP), and S-adenosylmethionine (SAM). Chronic alcohol consumption leads to significant reductions in SAM levels, thereby contributing to DNA hypomethylation. Similarly, ethanol metabolism alters the ratio of NAD+ to reduced NAD (NADH) and promotes the formation of reactive oxygen species and acetate, all of which impact epigenetic regulatory mechanisms. In addition to altered carbohydrate metabolism, induction of cell death, and changes in mitochondrial permeability transition, these metabolism-related changes can lead to modulation of epigenetic regulation of gene expression. Understanding the nature of these epigenetic changes will help researchers design novel medications to treat or at least ameliorate alcohol-induced organ damage.

Show MeSH
Related in: MedlinePlus