Effect of acute betaine administration on hepatic metabolism of S-amino acids in rats and mice.
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.
Kim
Sang K
SK
College of Pharmacy, Seoul National University, San 56-1 Shinrim-Dong, Kwanak-Ku, Seoul, South Korea.
Choi
Kwon H
KH
Kim
Young C
YC
D000480:Alkynes / Q000494:pharmacology; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001622:Betaine / Q000008:administration & dosage* / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D003540:Cystathionine / Q000378:metabolism; D003542:Cystathionine gamma-Lyase / Q000378:metabolism; D050558:Cysteine Dioxygenase; D049308:Dioxygenases; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008715:Methionine / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D010105:Oxygenases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism*; D013654:Taurine / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D000480:Alkynes; D000596:Amino Acids; D004791:Enzyme Inhibitors; D013654:Taurine; D003540:Cystathionine; D001622:Betaine; C009055:propargylglycine; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D008715:Methionine; D010105:Oxygenases; D049308:Dioxygenases; D050558:Cysteine Dioxygenase; D005723:gamma-Glutamyltransferase; D003542:Cystathionine gamma-Lyase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D005998:Glycine