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Nutrient Metabolism
Research Communication

Neither Methionine nor Nitrous Oxide Inactivation of Methionine Synthase Affect the Concentration of 5,10-Methylenetetrahydrofolate in Rat Liver¹

Department of Veterans Affairs Medical Center, Nashville, TN 37212 and Department of Biochemistry, Vanderbilt University Medical School, Nashville, TN 37232

²To whom correspondence should be addressed. E-mail: donald.w.horne{at}vanderbilt.edu.

5,10-Methylenetetrahydrofolate occupies a key position in folate-dependent one-carbon metabolism. It is involved directly in the biosynthesis of deoxythymidine, it can be converted to 10-formyltetrahydrofolate for purine synthesis and it may be reduced to 5-methyltetrahydrofolate for methylation of homocysteine to methionine. We have developed a HPLC method for measuring 5,10-methylenetetrahydrofolate in liver and we have used this method to investigate two conditions that perturb one-carbon metabolism: 1) administration of methionine and 2) administration of the anesthetic gas, nitrous oxide (N₂O). Rats were given 1.3 mmol/kg of methionine, and folate coenzymes in liver were measured. As expected, giving methionine resulted in an apparent increase in the concentration of 10-formyl- and tetrahydrofolate and an apparent decrease in 5-methyltetrahydrofolate concentration at 30 and 60 min. After 120 min, the concentrations of these coenzymes appeared to revert to control values. There was no apparent change in the concentration of 5,10-methylenetetrahydrofolate. Exposing rats to an atmosphere containing N₂O results in inactivation of methionine synthase and accumulation of 5-methyltetrahydrofolate at the expense of other folate coenzymes. In liver from rats breathing N₂O, 5-methyltetrahydrofolate increased, whereas there was no change in 5- or 10-formyltetrahydrofolates (P > 0.7 and P > 0.8, respectively). Tetrahydrofolate was not detected in liver from the N₂O group, whereas it constituted 24% of folates in the control group. The concentration of 5,10-methylenetetrahydrofolate was not significantly affected by N₂O (P > 0.18). These results suggest that the concentration of 5,10-methylenetetrahydrofolate is tightly regulated in liver.

KEY WORDS: • folic acid • one-carbon metabolism • 5,10-methylenetetrahydrofolate • methionine administration • nitrous oxide

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