Document Detail

Effect of acute betaine administration on hepatic metabolism of S-amino acids in rats and mice.
MedLine Citation:
PMID:  12732369     Owner:  NLM     Status:  MEDLINE    
Alterations of hepatic glutathione level by betaine were observed previously. In this study effects of betaine administration (1000 mg/kg, i.p.) on S-amino acid metabolism in rats and mice were investigated. Hepatic glutathione level decreased rapidly followed by marked elevation in 24 hr. Concentrations of S-adenosylmethionine, S-adenosylhomocysteine, and methionine were increased whereas cystathionine decreased significantly, suggesting that homocysteine generated in the methionine cycle is preferentially remethylated to methionine rather than being utilized for synthesis of cysteine. Hepatic cysteine concentration declined immediately, but plasma cysteine increased. Effect of betaine on hepatic cysteine uptake was estimated from the difference in cysteine concentration in major blood vessels connected to liver. Cysteine concentration either in the portal vein or abdominal aorta was not altered, however, a significant increase was noted in the hepatic vein, indicating that hepatic uptake of cysteine was decreased by betaine treatment. Activities of glutamate cysteine ligase, cystathionine beta-synthase, and cystathionine gamma-lyase were elevated in 24 hr. Pretreatment with propargylglycine, an irreversible inhibitor of cystathionine gamma-lyase, did not abolish the betaine-induced reduction of hepatic glutathione in 4 hr, however, the elevation at t=24 hr was blocked completely. In conclusion the present results indicate that betaine administration induces time-dependent changes on hepatic metabolism of S-amino acids. Betaine enhances metabolic reactions in the methionine cycle, but inhibits cystathionine synthesis and cysteine uptake, leading to a decrease in supply of cysteine for glutathione synthesis. Reduction in glutathione is subsequently reversed due to induction of cysteine synthesis and glutamate cysteine ligase activity.
Sang K Kim; Kwon H Choi; Young C Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  65     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2003 May 
Date Detail:
Created Date:  2003-05-06     Completed Date:  2003-06-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1565-74     Citation Subset:  IM    
College of Pharmacy, Seoul National University, San 56-1 Shinrim-Dong, Kwanak-Ku, Seoul, South Korea.
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MeSH Terms
Alkynes / pharmacology
Amino Acids / metabolism
Betaine / administration & dosage*,  pharmacology
Biological Transport / drug effects
Cystathionine / metabolism
Cystathionine gamma-Lyase / metabolism
Cysteine Dioxygenase
Enzyme Inhibitors / pharmacology
Glutamate-Cysteine Ligase / metabolism
Glutathione / metabolism
Glycine / analogs & derivatives*,  pharmacology
Liver / drug effects*,  metabolism
Methionine / metabolism
Mice, Inbred ICR
Oxygenases / metabolism
Rats, Sprague-Dawley
S-Adenosylhomocysteine / metabolism
S-Adenosylmethionine / metabolism*
Taurine / metabolism
gamma-Glutamyltransferase / metabolism
Reg. No./Substance:
0/Alkynes; 0/Amino Acids; 0/Enzyme Inhibitors; 107-35-7/Taurine; 107-43-7/Betaine; 29908-03-0/S-Adenosylmethionine; 56-40-6/Glycine; 56-88-2/Cystathionine; 63-68-3/Methionine; 64165-64-6/propargylglycine; 70-18-8/Glutathione; 979-92-0/S-Adenosylhomocysteine; EC 1.13.-/Oxygenases; EC 1.13.11.-/Dioxygenases; EC Dioxygenase; EC; EC gamma-Lyase; EC Ligase

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