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Effect of Dietary and Nitrous Oxide-Induced Vitamin B-12 Deficiency on Uptake of 5-Methyltetrahydrofolate by Isolated Rat Hepatocytes¹

Biochemistry Research Laboratory, Veterans Administration Medical Center and the Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37203

Prior exposure of rats to a mixture of nitrous oxide/oxygen (80/20) for 20 to 24 hours and feeding rats a diet deficient in vitamin B-12 and methionine for 23 weeks resulted in a 86 to 90% decrease in the activity of the vitamin B-12 dependent enzyme, 5-methyltetrahydrofolate-homocysteine methyltransferase (EC 4.2.99.10). In addition, deficient animals excreted some 15 times as much methylmalonic acid as controls indicating impaired functioning of the vitamin B-12-dependent enzyme, methylmalonyl CoA mutase (EC 5.4.99.2). Hepatocytes prepared from rats deficient in vitamin B-12 and methionine and from nitrous oxidetreated rats showed no impairment of the membrane transport of 5-methyl-tetrahydro-[G-³H]folic acid when compared to the respective controls. This observation was true both for the initial rate of entry and for the ability of these cells to accumulate this folate derivative. These findings support the "methyl trap" hypothesis and apparently rule out the "cellular transport" hypothesis for the folate-vitamin B-12 metabolic interrelationship.

KEY WORDS: • vitamin B-12 deficiency • nitrous oxide • 5-methyltetrahydrofolate transport • 5-methyltetrahydrofolate-homocysteine methyltransferase

¹ This work was supported in part by funds from the Medical Research Service of the Veterans Administration and Grant No. AM-15289 from the U.S. Public Health Service.

Manuscript received 12 June 1979.