Effects of betaine supplementation on hepatic metabolism of sulfur-containing amino acids in mice

Kim, Sang Kyum; Kim, Young C.

doi:10.1016/j.jhep.2005.01.017

Cited by 76 publications

(53 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Kwon et al (11) have also indicated that the function of sulfur-containing substances is signifi cantly disturbed by a high-fat liquid diet, suggesting a causal role of impairment of hepatic transsulfuration reactions in NAFLD. The effect of betaine supplementation on hepatic oxidative stress and transsulfuration reactions in animal models of fatty liver has been studied (13). As the liver is a central organ in the metabolism of sulfur-amino acids in mammals (14), the fi rst step in the transsulfuration reaction chain in the liver is the formation of S-adenosylmethionine (SAM) from methionine and ATP, which is catalyzed by methionine adenosyltransferase (MAT).…”

Section: Discussionmentioning

confidence: 99%

Effects of Dietary Supplementation with Betaine on a Nonalcoholic Steatohepatitis (NASH) Mouse Model

Kawakami

Han

Nakamura

et al. 2012

J Nutr Sci Vitaminol

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Effects of Dietary Supplementation with Betaine on a Nonalcoholic Steatohepatitis (NASH) Mouse Model

Kawakami

Han

Nakamura

et al. 2012

J Nutr Sci Vitaminol

View full text Add to dashboard Cite

“…Like GSH, HTau can be synthesized from the Cys residue of NAC. 29 HTau was found in very low concentrations in normal liver (0.05 Ϯ 0.02 mol/g ww), but increased considerably after administration of NAC and linearly up to 9.95 Ϯ 1.22 mol/g ww (Fig. 3).…”

Section: Nac Favors the Formation Of Htau Instead Of Gshmentioning

confidence: 95%

Metabolic insights into the hepatoprotective role of N-acetylcysteine in mouse liver

Zwingmann

Bilodeau

2006

Hepatology

View full text Add to dashboard Cite

The hepatoprotective mechanisms of N-acetylcysteine (NAC) in non-acetaminophen-induced liver injury have not been studied in detail. We investigated the possibility that NAC could affect key pathways of hepatocellular metabolism with or without changes in glutathione (GSH) synthesis. Hepatocellular metabolites and high-energy phosphates were quantified from mouse liver extracts by 1 H-and 31 P-NMR (nuclear magnetic resonance) spectroscopy. 13 C-NMR-isotopomer analysis was used to measure [U-13 C]glucose metabolism through pyruvate dehydrogenase (PDH) and pyruvate carboxylase (PC). NAC (150-1,200 mg/kg) increased liver concentrations of GSH from 8.60 ؎ 0.48 to a maximum of 12.95 ؎ 1.03 mol/g ww, whereas hypotaurine (HTau) concentrations increased from 0.05 ؎ 0.02 to 9.95 ؎ 1.12 mol/g ww. The limited capacity of NAC to increase GSH synthesis was attributed to impaired glucose metabolism through PC. However, 300 mg/kg NAC significantly increased the fractional 13 C-enrichment in Glu (from 2.08% ؎ 0.26% to 4.00% ؎ 0.44%) synthesized through PDH, a key enzyme for mitochondrial energy metabolism. This effect could be uncoupled from GSH synthesis and was associated with the prevention of liver injury induced by tert-butylhydroperoxide and 3-nitropropionic acid. N -acetylcysteine (NAC) is the most widely administered antidote in acetaminophen intoxication. [1][2][3][4] In this setting, protection by NAC is believed to be attributable to its ability to regenerate glutathione (GSH) stores due to its capacity to provide cysteine (Cys) residues. However, NAC has also been shown to improve patient outcome after late administration, 5,6 pointing toward mechanisms independent from GSH replenishment. Furthermore, because NAC is recognized as an antioxidant, it might be useful in the setting of liver injuries different from those caused by acetaminophen intoxication. [6][7][8][9][10][11] NAC has also been reported to improve oxygen delivery, 4 to increase systemic oxygen consumption, 12 and to have beneficial effects on liver blood flow and function. 6,8,10 Because liver oxygen consumption is coupled with aerobic oxidation of energy substrates in the mitochondrial tricarboxylic acid (TCA) cycle, we hypothesize that NAC might improve hepatocellular energy metabolism. This effect might be salutary in the setting of nonacetaminophen-induced liver injury.We were particularly interested in investigating how NAC is involved in hepatocellular metabolic pathways and whether these changes are associated with modulation of GSH synthesis. The liver is unique in its metabolic activity and harbors many interrelated pathways. Apart

show abstract

“…Ophtalmate is an indicator of the activity of glutathione synthesis because this is produced by the enzymes of glutathione synthesis, gamma glutamylcysteine synthetase and glutathione synthetase (Soga et al, 2006). Cysteine, which is a component of GSH (Kim et al, 2003;Wu et al, 2004) and a rate-limiting amino acid for GSH synthesis (Lu, 2000), was decreased only in the HFD mice. These facts indicated increased synthesis of GSH in the liver of the HFD mice treated with TA.…”

Section: Discussionmentioning

confidence: 99%

“…Fig. 5 shows the metabolic pathway of GSH (Kim et al, 2003;Soga et al, 2006;Wu et al, 2004;Lu, 1999) and the changes in the amount of each metabolite at 8 and 24 hr after TA administration.…”

Section: Hepatic Oxidative Stress Induced By Ta Administration (Expermentioning

confidence: 99%

“…Several metabolites are known to be involved in GSH metabolism (Kim et al, 2003;Soga et al, 2006;Wu et al, 2004;Lu, 1999), and hence, the status of GSH metabolism can be estimated by investigation of each of the metabolites using metabolomics analysis (Agudo-Barriuso et al, 2013). On the other hand, gamma-glutamylcysteine synthetase is the rate-limiting enzyme of GSH synthesis (Lu, 2000).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hepatic glutathione contributes to attenuation of thioacetamide-induced hepatic necrosis due to suppression of oxidative stress in diet-induced obese mice

et al. 2015

View full text Add to dashboard Cite

-We previously reported that hepatic necrosis induced by thioacetamide (TA), a hepatotoxicant, was attenuated in mice fed a high-fat diet (HFD mice) in comparison with mice fed a normal rodent diet (ND mice). In this study, we focused on investigation of the mechanism of the attenuation. Hepatic content of thiobarbituric acid reactive substances (TBARS), an oxidative stress marker, significantly increased in ND mice at 24 and 48 hr after TA administration in comparison to that in vehicle-treated ND mice. At these time points, severe hepatic necrosis was observed in ND mice. Treatment with an established antioxidant, butylated hydroxyanisole, attenuated the TA-induced hepatic necrosis in ND mice. In contrast, in HFD mice, hepatic TBARS content did not increase, and hepatic necrosis was attenuated in comparison with ND mice at 24 and 48 hr after TA dosing. Metabolomics analysis regarding hepatic glutathione, a biological antioxidant, revealed decreased glutathione and changes in the amount of glutathione metabolism-related metabolites, such as increased ophtalmate and decreased cysteine, and this indicated activation of glutathione synthesis and usage in HFD mice. Finally, after treatment with L-buthionine-S,R-sulfoxinine, an inhibitor of glutathione synthesis, TA-induced hepatic necrosis was enhanced and hepatic TBARS contents increased after TA dosing in HFD mice. These results suggested that activated synthesis and usage of hepatic GSH, which suppresses hepatic oxidative stress, is one of the factors that attenuate TA-induced hepatic necrosis in HFD mice.

show abstract

Effects of betaine supplementation on hepatic metabolism of sulfur-containing amino acids in mice

Cited by 76 publications

References 46 publications

Effects of Dietary Supplementation with Betaine on a Nonalcoholic Steatohepatitis (NASH) Mouse Model

Effects of Dietary Supplementation with Betaine on a Nonalcoholic Steatohepatitis (NASH) Mouse Model

Metabolic insights into the hepatoprotective role of N-acetylcysteine in mouse liver

Hepatic glutathione contributes to attenuation of thioacetamide-induced hepatic necrosis due to suppression of oxidative stress in diet-induced obese mice

Contact Info

Product

Resources

About