title: Impaired one carbon metabolism and DNA methylation in alcohol toxicity.
abstract: Excessive alcohol consumption is a prominent problem and one of the major causes of mortality and morbidity around the world. Long-term, heavy alcohol consumption is associated with a number of deleterious health consequences, such as cancer, heart and liver disease, a variety of neurological, cognitive, and behavioral deficits. Alcohol consumption is also associated with developmental defects. The causes of alcohol-induced toxicity are presently unclear. One of the mechanisms underlying alcohol toxicity has to do with its interaction with folic acid/homocysteine or one-carbon metabolism (OCM). OCM is a major donor of methyl groups for methylation, particularly DNA methylation critical for epigenetic regulation of gene expression, and its disturbance may compromise DNA methylation, thereby affecting gene expression. OCM disturbance mediated by nutrient deficits is a well-known risk factor for various disorders and developmental defects (e.g., neural tube defects). In this review, we summarize the role of OCM disturbance and associated epigenetic aberrations in chronic alcohol-induced toxicity. In this review, we summarize the role of one-carbon metabolism (OCM) aberrations in chronic alcohol-induced toxicity. OCM is a major donor of methyl groups for methylation reactions, particularly DNA methylation critical for epigenetic regulation of gene expression. Alcohol interference with OCM and consequent reduced availability of methyl groups, improper DNA methylation, and aberrant gene expression can play a causative role in alcohol toxicity.
authors: Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, Texas, USA.
authors: Inna I
authors: II
authors: Kruman
authors: Anna-Kate
authors: AK
authors: Fowler
mesh_terms: D000328:Adult; D000435:Alcoholic Intoxication / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D002244:Carbon / Q000378:metabolism*; D019175:DNA Methylation / Q000187:drug effects*; D044127:Epigenesis, Genetic / Q000502:physiology; D006801:Humans; D012307:Risk Factors
chemical_list: D002244:Carbon
keywords: DNA methylation; alcohol toxicity; one-carbon metabolism