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

Abstract

Rees WD. Effects of methyl-deficient diets on methionine and homocysteine metabolism in the pregnant rat. Am J Physiol Endocrinol Metab 302: E1531-E1540, 2012. First published March 27, 2012 doi:10.1152/ajpendo.00668.2011.-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. Rates of homocysteine remethylation in maternal and fetal tissues on days 11, 19, and 21 of gestation were measured in pregnant rats fed diets with limiting or surplus amounts of folic acid and choline at two levels of methionine and then infused with L-[1-13 C, 2 H3-methyl]methionine. The rate of homocysteine remethylation was highest in maternal liver and declined as gestation progressed. Diets deficient in folic acid and choline reduced the production of methionine from homocysteine in maternal liver only in 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 gestation, but, during this period, fetal tissues, especially the liver, synthesized methionine from homocysteine. Greater enrichment of homocysteine in maternal plasma than placenta, even in animals fed the most-deficient diets, shows that the placenta did not contribute homocysteine to maternal plasma. Methionine synthesis from homocysteine in fetal tissues was maintained or increased when the 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 that these rates are protected to some extent within fetal tissues.folate; choline; fetal development; stable isotopes NUMEROUS LARGE-SCALE CLINICAL trials have clearly established the value of folic acid supplements in pregnancy (23). In addition to a marked reduction in the frequency of neural tube defects and other congenital malformations of the fetus (7, 13), improved folate status is also associated with enhanced fetal growth (17). Elevated plasma total (t-) homocysteine concentration, a marker of changes in methyl metabolism, is also recognized as a risk factor for a number of adverse pregnancy outcomes in humans (11,24,27). It has been suggested that folate supplements improve fetal development by increasing the recycling of homocysteine to methionine through the methionine cycle (Fig. 1) (1, 2, 8).The relationship between the availability of folic acid and associated methyl donors in the maternal diet and the flow through the methionine cycle in the tissues of the mother and the developing fetus is poorly quantified. Studies of pregnant rats show that methyl-deficient diets low in folic acid, choline, and methionine increase t-homocysteine concentrations in maternal and fetal plasma (9). While the enzymes of the methionin...

Choline Supplementation Prevents a Hallmark Disturbance of Kwashiorkor in Weanling Mice Fed a Maize Vegetable Diet: Hepatic Steatosis of Undernutrition

“…Metabolic data suggested that the prevention of hepatic steatosis in mice fed a choline-supplemented MVD was associated with a significant increase in the hepatic availability of methyl groups. This finding is consistent with the observation that VLDL export from the liver has an absolute requirement for PC synthesized by PEMT [ 35 , 48 ] a methyl group dependent enzyme. Overall, these findings provide insight into the molecular mechanisms influenced by the addition of choline to a MVD, and highlight the potential role of one-carbon nutrients, such as choline, for preventing hepatic steatosis in children subsisting on low protein plant based diets that are associated with increased risk for kwashiorkor malnutrition.…”

Plasma low-molecular-weight thiol/disulphide homeostasis as an early indicator of global and focal cerebral ischaemia

“…According to the literature, the levels of total plasma LMWT in rats are 75-200 µmol/l (Cys), 5-22 µmol/l (GSH) and 3.2-14.4 µmol/l (Hcy) [29][30][31]. It should be noted that age and diet (B 9 , fatty acid consumption) have a great impact on the total LMWT levels [30,32]. The levels of reduced forms of Cys, GSH and Hcy are about 17, 11 and >0.5 µmol/l, respectively, in rat plasma [32,33].…”

Association between methylation potential and nutrient metabolism throughout the reproductive cycle of sows

“…The developing foetus depends on its mother for the supply of nutrients to support the high rates of cell division occurring during the early life stages (Rees, Wilson, & Maloney, ). The placenta, as the interface between maternal and foetal circulation, plays a key role in regulating foetal methionine supply (Wilson et al, ), which is necessary for protein synthesis (Lamers et al, ) and for the production of S‐adenosylmethionine (SAM) (Fux et al, ). Placental growth, which is important for the growth and development of the foetuses via nutrient transfer, is affected by a variety of environmental and other factors, including DNA methylation and maternal nutritional status (Fowden, Sibley, Reik, & Constancial, ).…”