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Folate polyglutamate synthetase activity in the cobalamin-inactivated rat
Abstract:
Exposure to N2O inactivates cob[I]alamin and interferes with the activity of methionine synthetase, of which cob[I]alamin is a coenzyme. Less directly, it stops the formation of folate polyglutamate from tetrahydrofolates. Studies on the activity of folate polyglutamate synthetase in rat liver in vivo were carried out. The synthetase activity increased after exposure to N2O for up to 48 h, but longer exposure was accompanied by a return of activity to baseline values. The rise in synthetase activity was prevented by supplying methionine, 5'-methylthioadenosine or 5-formyltetrahydrofolate. The fall in folate polyglutamate synthetase activity after 48 h was accompanied by a restoration of hepatic synthesis of folate polyglutamate despite continuation of N2O exposure.
Insights
Nitrous oxide (N2O) exposure impacts cobalamin-dependent enzymes, affecting folate metabolism. Supplementation can mitigate these effects, restoring folate polyglutamate synthesis in rats.
Area of Science:
- Biochemistry
- Nutritional Science
- Toxicology
Background:
- Nitrous oxide (N2O) inactivates cob[I]alamin, a crucial coenzyme for methionine synthetase.
- N2O exposure also inhibits the conversion of tetrahydrofolates to folate polyglutamate.
- Understanding the impact on folate polyglutamate synthetase is vital for metabolic health.
Purpose of the Study:
- To investigate the in vivo activity of folate polyglutamate synthetase in rat liver following N2O exposure.
- To determine the effects of varying durations of N2O exposure on synthetase activity.
- To explore potential interventions to counteract N2O-induced metabolic disturbances.
Main Methods:
- Rats were exposed to N2O for varying durations.
- Folate polyglutamate synthetase activity was measured in rat liver tissue.
- Intervention groups received methionine, 5'-methylthioadenosine, or 5-formyltetrahydrofolate.
Main Results:
- Folate polyglutamate synthetase activity initially increased with N2O exposure up to 48 hours.
- Longer N2O exposure (beyond 48 hours) led to a decrease in synthetase activity towards baseline levels.
- Supplementation with methionine, 5'-methylthioadenosine, or 5-formyltetrahydrofolate prevented the rise in synthetase activity.
- Despite continued N2O exposure, hepatic folate polyglutamate synthesis was restored after 48 hours, coinciding with decreased synthetase activity.
Conclusions:
- N2O exposure has a biphasic effect on hepatic folate polyglutamate synthetase activity.
- Specific nutrient supplementation can modulate the response to N2O.
- The liver can partially restore folate polyglutamate synthesis despite ongoing N2O exposure.