Alterations in hepatic metabolism of sulfur-containing amino acids induced by ethanol in rats

Kim, S. K.; Seo, Jinyoung; Jung, Young Suk; Kwak, Ho Young; Kim, Y. C.

doi:10.1007/s00726-002-0324-6

Cited by 33 publications

(11 citation statements)

References 45 publications

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“…Earlier studies showed that chronic exposure to ethanol decreased SAM and increased SAH [3,4,16,21–24]. We reproduced these effects with an acute exposure to ethanol as well as propanol.…”

Section: Discussionsupporting

confidence: 71%

Ethanol exposure modulates hepatic S-adenosylmethionine and S-adenosylhomocysteine levels in the isolated perfused rat liver through changes in the redox state of the NADH/NAD+ system

Watson

Song

Kirpich

et al. 2011

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Methionine metabolism is disrupted in patients with alcoholic liver disease, resulting in altered hepatic concentrations of S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), and other metabolites. The present study tested the hypothesis that reductive stress mediates the effects of ethanol on liver methionine metabolism. Isolated rat livers were perfused with ethanol or propanol to induce a reductive stress by increasing the NADH/NAD+ ratio, and the concentrations of SAM and SAH in the liver tissue were determined by high-performance liquid chromatography. The increase in the NADH/NAD+ ratio induced by ethanol or propanol was associated with a marked decrease in SAM and an increase in SAH liver content. 4-Methylpyrazole, an inhibitor the NAD+-dependent enzyme alcohol dehydrogenase, blocked the increase in the NADH/NAD+ ratio and prevented the alterations in SAM and SAH. Similarly, co-infusion of pyruvate, which is metabolized by the NADH-dependent enzyme lactate dehydrogenase, restored the NADH/NAD+ ratio and normalized SAM and SAH levels. The data establish an initial link between the effects of ethanol on the NADH/NAD+ redox couple and the effects of ethanol on methionine metabolism in the liver.

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Section: Discussionsupporting

confidence: 71%

Ethanol exposure modulates hepatic S-adenosylmethionine and S-adenosylhomocysteine levels in the isolated perfused rat liver through changes in the redox state of the NADH/NAD+ system

Watson

Song

Kirpich

et al. 2011

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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“…In the rats fed HF, hepatic cysteine was unchanged, but both concentration and activity of CDO increased significantly, suggesting that a signal other than cysteine availability may also be involved in the regulation of CDO and GCL. Previously, we observed that cysteine catabolism to taurine was paradoxically increased in rats challenged with ethanol (36,37). The physiological importance of enhanced taurine synthesis under oxidative stress needs to be explored in future studies.…”

Section: Discussionmentioning

confidence: 96%

Impaired Sulfur-Amino Acid Metabolism and Oxidative Stress in Nonalcoholic Fatty Liver Are Alleviated by Betaine Supplementation in Rats

Kwon

Jung

Kim

et al. 2009

The Journal of Nutrition

116

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Nonalcoholic fatty liver is involved in the development of nonalcoholic steatohepatitis and chronic liver injury. Impairment of hepatic transsulfuration reactions is suggested to be critically linked with alcoholic liver injury, but its role in nonalcoholic fatty liver remains unknown. We examined the early changes in sulfur-amino acid metabolism and their implication in nonalcoholic fatty liver disease (NAFLD). Male rats were provided with a standard liquid diet or a high-fat liquid diet (HF) for 3 wk. An additional group of rats received the HF diet supplemented with betaine (1%). HF diet intake elevated hepatic triglyceride and serum tumor necrosis factor-alpha (TNFalpha) concentrations. Antioxidant capacity of liver cytosol against hydroxyl and peroxyl radicals was reduced significantly. Hepatic S-adenosylmethionine (SAM) and glutathione (GSH) decreased, but hypotaurine and taurine concentrations increased. Methionine adenosyltransferase (MAT) activity, not its concentration, was depressed, whereas both activity and concentration of cysteine dioxygenase and GSH S-transferase were elevated. Betaine supplementation of the HF diet inhibited hepatic fat accumulation and serum TNFalpha elevation. The decrease in cytosolic antioxidant capacity was also prevented. MAT activity and its concentration were induced significantly. Hepatic SAM and GSH increased and elevation of hypotaurine and taurine was depressed. The results indicate that the metabolism of S-containing substances is significantly disturbed by the HF diet, suggesting a causal role of impairment of hepatic transsulfuration reactions in NAFLD. Betaine supplementation protects the liver from nonalcoholic steatosis and oxidative stress most probably via its effects on the transsulfuration reactions.

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“…Activities of MAT, SAHH, BHMT, MS, CβS, CDO and GCL were determined according to our previous methods ( Kim et al ., 2003 ; Kwak et al ., 2015 ).…”

Section: Methodsmentioning

confidence: 99%

Age-Related Changes in Sulfur Amino Acid Metabolism in Male C57BL/6 Mice

Jeon

Kwak

et al. 2018

Biomolecules & Therapeutics

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Alterations in sulfur amino acid metabolism are associated with an increased risk of a number of common late-life diseases, which raises the possibility that metabolism of sulfur amino acids may change with age. The present study was conducted to understand the age-related changes in hepatic metabolism of sulfur amino acids in 2-, 6-, 18- and 30-month-old male C57BL/6 mice. For this purpose, metabolite profiling of sulfur amino acids from methionine to taurine or glutathione (GSH) was performed. The levels of sulfur amino acids and their metabolites were not significantly different among 2-, 6- and 18-month-old mice, except for plasma GSH and hepatic homocysteine. Plasma total GSH and hepatic total homocysteine levels were significantly higher in 2-month-old mice than those in the other age groups. In contrast, 30-month-old mice exhibited increased hepatic methionine and cysteine, compared with all other groups, but decreased hepatic S-adenosylmethionine (SAM), S-adenosylhomocysteine and homocysteine, relative to 2-month-old mice. No differences in hepatic reduced GSH, GSH disulfide, or taurine were observed. The hepatic changes in homocysteine and cysteine may be attributed to upregulation of cystathionine β-synthase and down-regulation of γ-glutamylcysteine ligase in the aged mice. The elevation of hepatic cysteine levels may be involved in the maintenance of hepatic GSH levels. The opposite changes of methionine and SAM suggest that the regulatory role of SAM in hepatic sulfur amino acid metabolism may be impaired in 30-month-old mice.

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Alterations in hepatic metabolism of sulfur-containing amino acids induced by ethanol in rats

Cited by 33 publications

References 45 publications

Ethanol exposure modulates hepatic S-adenosylmethionine and S-adenosylhomocysteine levels in the isolated perfused rat liver through changes in the redox state of the NADH/NAD+ system

Ethanol exposure modulates hepatic S-adenosylmethionine and S-adenosylhomocysteine levels in the isolated perfused rat liver through changes in the redox state of the NADH/NAD+ system

Impaired Sulfur-Amino Acid Metabolism and Oxidative Stress in Nonalcoholic Fatty Liver Are Alleviated by Betaine Supplementation in Rats

Age-Related Changes in Sulfur Amino Acid Metabolism in Male C57BL/6 Mice

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