The methionine cycle and pregnancy in the rat
This study aims to identify in the non-pregnant rat and pregnant dam those tissues with the greatest methionine cycle activity and those that are most sensitive to methyl group deficiency. In addition, as human studies rely heavily on the plasma measurements, this study also aims to investigate whether plasma metabolites of homocysteine and methionine reflect tissue metabolism. This study investigated the kinetics of methionine metabolism in the rat using an L-[1-13C, 2H3] methionine tracer that is converted to [1-13C] homocysteine and [1-13C] methionine by passage through the methionine cycle. The effect of the methionine, folate and choline content in the diet was studied by measuring the conversion of homocysteine to methionine within tissue of the pregnant and non-pregnant rat. Tissue homocysteine methylation was estimated from the ratio of [1-13C] methionine to [1-13C, 2H3] methionine in comparison with the same ratio in the plasma. The main findings of this study were that the liver and the pancreas were the main sites of homocysteine methylation within the rat, with the pancreas also emerging as the major contributor to plasma homocysteine and synthesised methionine. Additionally, it was observed that ht e fetus was able to compensate for a reduction in homocysteine methylation as a consequence of folate and choline deficiency within the dam until day 19 of gestation. After this time, however, the fetus cannot increase the conversion of homocysteine to methionine to compensate. This study also indicated that as gestation progresses maternal methionine synthesis was reduced to conserve folate and choline for use within the fetus.