Effects of nitrous oxide-induced inactivation of cobalamin on methionine and S-adenosylmethionine metabolism in the rat.
Inhalation of nitrous oxidises cobalamin and, in turn, inactivates methionine synthetase which forms methionine from homocysteine and which requires cob[I]alamin as a co-factor. This study was planned to determine the effect of virtual cessation of methionine synthesis via a cobalamin-dependent pathway, on tissue levels of methionine, S-adenosylmethionine and on related enzymes. The level of methionine in liver fell initially after exposure to N2O but was restored to pre-N2O levels after 6 days despite continuing N2O exposure. Brain methionine fell within 12 h of N2O exposure but the fall was not significant. The restoration of methionine levels is accompanied by an increase in activity of betaine homocysteine methyltransferase in liver but this enzyme was not detected in brain. The activity of methionine synthetase remained very low in both liver and brain as long as N2O inhalation was continued. There was an initial rise in liver S-adenosylmethionine levels followed by a steady fall to 40% of its initial level after 11 days of N2O exposure. However, there was no change in the level of S-adenosylmethionine in brain during this period. The data indicate that either brain meets its requirement by increased methionine uptake from plasma or that there are alternate pathways in brain for methionine synthesis other than those requiring a cobalamin coenzyme.
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000037:antagonists & inhibitors; D000818:Animals; D050940:Betaine-Homocysteine S-Methyltransferase; D001921:Brain / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D008715:Methionine / Q000378:metabolism*; D008780:Methyltransferases / Q000378:metabolism; D009609:Nitrous Oxide / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012436:S-Adenosylmethionine / Q000378:metabolism*; D014805:Vitamin B 12 / Q000037:antagonists & inhibitors / Q000502:physiology*
D012436:S-Adenosylmethionine; D008715:Methionine; D008780:Methyltransferases; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D050940:Betaine-Homocysteine S-Methyltransferase; D009609:Nitrous Oxide; D014805:Vitamin B 12