부산대학교 도서관

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1530-0277.2006.00147.x Byline: Jesus A Villanueva (1), Farah Esfandiari (1), Donna H Wong (1), Iram Ahmad (1), Stepan Melnyk (2), SJill James (2), Charles H Halsted (1) Keywords: Glutathione; Methionine; Alcoholic Liver Disease Abstract: Background: Alcoholic liver disease is associated with abnormalities of methionine metabolic enzymes that may contribute to glutathione depletion. Previously, we found that feeding micropigs a combination of ethanol with a folate-deficient diet resulted in the greatest decreases in S-adenosylmethionine and glutathione and increases in liver S-adenosylhomocysteine and oxidized disulfide glutathione. Methods: To study the mechanisms of glutathione depletion, we analyzed the transcripts and activities of enzymes involved in its synthesis and metabolism in liver and plasma specimens that were available from the same micropigs that receive folate-sufficient or folate-depleted diets with or without 40% of energy as ethanol for 14 weeks. Results: Ethanol feeding, folate deficiency, or their combination decreased liver and plasma glutathione and the activities of hepatic copper-zinc superoxide dismutase and glutathione peroxidase and increased the activity of manganese superoxide dismutase and glutathione reductase. Hepatic levels of cysteine and taurine were unchanged while plasma cysteine was increased in the combined diet group. Cystathionine [beta]-synthase transcripts and activity were unaffected by ethanol feeding, while the activities of other transsulfuration enzymes involved in glutathione synthesis were increased. Glutathione transferase transcripts were increased 4-fold and its mean activity was increased by 34% in the combined ethanol and folate-deficient diet group, similar in magnitude to the observed 36% reduction in hepatic glutathione. Conclusions: Chronic ethanol feeding and folate deficiency acted individually or synergistically to affect methionine metabolism in the micropig by depleting glutathione pools and altering transcript expressions and activities of enzymes involved in its synthesis, utilization, and regeneration. The data suggest that the observed decrease in hepatic glutathione during ethanol feeding reflects its increased utilization to meet increased antioxidant demands, rather than reduction in its synthesis. Author Affiliation: (1)Department of Internal Medicine, University of California, Davis, California (2)Department of Pediatrics, Arkansas Children's Hospital Research Institute, Little Rock, Arkansas Article History: Received for publication January 17, 2006; accepted March 13, 2006. Article note: Reprint requests: Jesus A. Villanueva, DVM, PhD, Division of Clinical Nutrition, #5303 Genome & Biomedical Sciences Facility, 451 Health Sciences Drive, UC Davis School of Medicine, Davis, CA 95616; Fax: 530-752-3470; E-mail: javillanueva@ucdavis.edu