The effects of methyl-deficient diets on methionine and homocysteine metabolism in the pregnant rat

Although the importance of methyl metabolism in fetal development is well recognized, there is limited information on the dynamics of methionine flow through maternal and fetal tissues and on how this is related to circulating total homocysteine concentrations. Pregnant rats were fed diets with either limiting or surplus amounts of folic acid and choline at two levels of methionine and then infused with L-[1-13C, 2H3-methyl]-methionine to measure the rates of homocysteine remethylation in maternal and fetal tissues on 11, 19 and 21 days of gestation. The highest rates of homocysteine remethylation occurred in the maternal liver. The rate declined as gestation progressed. Diets deficient in folic acid and choline reduced the production of methionine from homocysteine in the maternal liver only for the animals fed a methionine-limited diet. Throughout gestation the pancreas exported homocysteine for methylation within other
tissues. Little or no methionine cycle activity was detected in the placenta at days 19 and 21 of pregnancy but, during this period, fetal tissues, especially the liver,
synthesized methionine from homocysteine. The enrichment of homocysteine in the maternal plasma was greater than that in the placenta even in the animals fed the most deficient diets, showing that placenta did not contribute homocysteine to the maternal plasma. Methionine synthesis from homocysteine in fetal tissues was either maintained or increased when dams were fed folate and choline deficient methionine restricted diets. This study shows that methyl deficient diets decrease the remethylation of homocysteine within maternal tissues; but these rates are protected to some extent within fetal tissues.