Developmental changes in the activity of phosphatidylethanolamine <i>N</i>-methyltransferases in rat brain

Blusztajn, Jan Krzysztof; Zeisel, Steven H.; Wurtman, Richard J.

doi:10.1042/bj2320505

Cited by 56 publications

(38 citation statements)

References 36 publications

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“…This observation is consistent with the finding that methionine synthase activity was similar in fetal and maternal liver (25). However, methionine synthase activity may also be present in other fetal tissues, including the brain (3), and the present data cannot rule out the possibility that these tissues also make a contribution. This tissue-specific methylation may play vital, but as yet unidentified, metabolic roles.…”

Section: Methionine Metabolism In the Fetussupporting

confidence: 82%

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

Wilson

Holtrop

Calder

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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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...

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Section: Methionine Metabolism In the Fetussupporting

confidence: 82%

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

Wilson

Holtrop

Calder

et al. 2012

American Journal of Physiology-Endocrinology and Metabolism

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“…The neonatal PEMT has a high affinity for SAM and methylates four times faster than the adult liver version. Its concentration also increases 2-fold from neonatal days 5 to 20, a period of rapid rat brain growth (Blusztajn, et al, 1985).…”

Section: Polyunsaturated Fatty Acid Synthesis May Contribute To Ntdsmentioning

confidence: 99%

A hypothesis linking low folate intake to neural tube defects due to failure of post-translation methylations of the cytoskeleton

Björklund¹,

Gordon²

2006

Int. J. Dev. Biol.

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Neural tube defects are serious congenital malformations which can be prevented by periconceptional folic acid supplementation. We hypothesize that folic acid provides the methyl group used for post-translational methylation of arginine and histidine in the highly conserved regulatory domains of the cytoskeleton and that these are required for neural tissue differentiation. Presumptive neural tissue has an unusually high need for folates due to the activity of phosphoethanolamine methyl transferase in producing neural tissue specific lipids at a time when the cytoskeleton is also competing for methylation. According to the cell state splitter hypothesis, the cytoskeleton is required to coordinate the spatial and temporal component of differentiation. When folate supply is low and the cytoskeleton is not methylated properly, the result is a neural tube defect due to failure of this coordination.

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“…This enzyme uses S-adenosylmethionine as a methyl donor and forms a new choline moiety (13). When fed a diet deficient in choline, Pemt−/− mice developed fatty liver and severe liver damage and died; a choline-supplemented diet prevented this outcome (144) and reversed hepatic damage if begun early enough (143).…”

Section: Dietary Intake and Endogenous Synthesis Of Cholinementioning

confidence: 99%

“…In the other pathway, phosphatidylethanolamine is sequentially methylated to form phosphatidylcholine, using S-adenosylmethionine as the methyl donor. The latter pathway is most active in liver, but has been identified in many other tissues, including brain and mammary gland (13,138,154). This pathway is discussed in detail below.…”

Section: Introductionmentioning

confidence: 99%

Choline: Critical Role During Fetal Development and Dietary Requirements in Adults

2006

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Choline is an essential nutrient needed for the structural integrity and signaling functions of cell membranes; for normal cholinergic neurotransmission; for normal muscle function; for lipid transport from liver; and it is the major source of methyl groups in the diet. Choline is critical during fetal development, when it influences stem cell proliferation and apoptosis, thereby altering brain and spinal cord structure and function and influencing risk for neural tube defects and lifelong memory function. Choline is derived not only from the diet, but from de novo synthesis as well. Though many foods contain choline, there is at least a twofold variation in dietary intake in humans. When deprived of dietary choline, most men and postmenopausal women developed signs of organ dysfunction (fatty liver or muscle damage), while less than half of premenopausal women developed such signs. Aside from gender differences, there is significant variation in the dietary requirement for choline that can be explained by very common genetic polymorphisms.

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Developmental changes in the activity of phosphatidylethanolamine N-methyltransferases in rat brain

Cited by 56 publications

References 36 publications

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

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

A hypothesis linking low folate intake to neural tube defects due to failure of post-translation methylations of the cytoskeleton

Choline: Critical Role During Fetal Development and Dietary Requirements in Adults

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