Methionine kinetics in adult men: effects of dietary betaine onl-[2H3-methyl-1 -13C]methionine1–3

Storch, Kenneth J.; Wagner, David; Young, Vernon R.

doi:10.1093/ajcn/54.2.386

Cited by 56 publications

(51 citation statements)

References 34 publications

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“…We have sought to monitor methionine cycle activity in maternal and fetal tissues of the pregnant rat by infusing L- [1-13 C,5-methyl- 2 H 3 ]methionine (21,22). This tracer was infused into rats offered diets differing in folate, choline, and methionine content at various stages of pregnancy (days 11, 19, and 21 of gestation).…”

mentioning

confidence: 99%

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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confidence: 99%

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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“…This enzyme, present primarily in the liver and kidney, is induced by betaine and can remethylate up to 25% of total homocysteine flux. 12 Betaine improved biochemical control in previous studies of patients with B6-nonresponsive C␤S deficiency. 13 Subsequent studies confirmed their observations that betaine treatment decreased total plasma homocysteine, in both plasma and cerebrospinal fluid.…”

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confidence: 82%

Cystathionine β-synthase deficiency: Effects of betaine supplementation after methionine restriction in B6-nonresponsive homocystinuria

Singh

Kruger

Wang

et al. 2004

Genetics in Medicine

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“…Indeed, the betaine content of infant formulas were reported to be within the range of breast milk, which was largely dependent on maternal betaine intakes (Sakamoto et al, 2001). Taken together, all of the reported estimates of betaine intake are well below supplemental levels that often provide 3--6 g betaine/d Ronge and Kjellman, 1996;Storch et al, 1991). However, because there is no dietary betaine requirement, it is unclear how variable intakes of this methyl donor affect methyl metabolism, or if there is a demand for dietary betaine in early life.…”

Section: Betainementioning

confidence: 95%

“…For example, in men supplemented with 3 g betaine/d under otherwise normal dietary conditions, the whole body rate of remethylation was unchanged despite increased transmethylation and decreased protein synthesis (Storch et al, 1991). This is confusing due to convincing evidence that betaine is effective at enhancing remethylation in adults (Mudd et al, 1980;Mudd and Poole, 1975) and protein deposition in swine (Fernández--Fígares et al, 2002).…”

Section: Betainementioning

confidence: 99%

“…Within the scope of development, the plasticity of transmethylation is of concern. Indeed, in vivo transmethylation rates are responsive to dietary and physiological changes such as betaine supplementation in adults (Storch et al, 1991), progression of pregnancy (Dasarathy et al, 2010), and sulfur--amino acid restriction in piglets (Bauchart-- There are at least 50 described reactions of transmethylation (Schubert et al, 2003), however it has been estimated that there may be >300 methyltransferase enzymes that employ SAM as substrate (J. T. Brosnan and M. E. Brosnan, 2006;Katz et al, 2003). Due to its vast nature it is difficult to predict the effects of a global reduction in transmethylation during development.…”

Section: Transmethylationmentioning

confidence: 99%

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The effects of dietary methyl donors on methionine partitioning in the neonatal piglet

Robinson

2015

Appl. Physiol. Nutr. Metab.

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The metabolism of the indispensable amino acid methionine is critical during development. Methionine is used to synthesize protein for growth and, using the methionine cycle, it is the precursor of >50 critical nutrients and contributes to epigenetic regulation. Therefore, the dietary methionine requirement must factor all the potential roles of methioine. Three major processes summarize the methionine cycle: transmethylation (TM), which transfers methyl groups to nutrient precursors and DNA; transsulfuration (TS), which represents methionine disposal; and remethylation (RM), which resynthesizes methionine using the dietary methyl donors folate and choline (via betaine). Dietary intakes of folate vary drastically, and choline intakes are often below the adequate intakes during preganancy and in early life, which we hypothesized would influence the methionine requirement. To test our hypothesis, we fed 4--8 day old neonatal piglets a low--methionine diet that was either deficient (MD-), or replete (MS+), in dietary methyl donors. We evaluated how methionine was balanced between the major TM reactions and protein synthesis. The MD-group exhibited marked differences in TM as creatine synthesis was ≈30% less (p<0.05), and phosphatidylcholine synthesis was ≈60% more (p<0.05) during MD-feeding. Interestingly, while MD-feeding did not affect liver protein synthesis, the methionine availablity and protein synthesis were lower in skeletal muscle of the MD-vs. MS+ animals (p<0.05). Furthermore, whole body protein turnover was also reduced during MD-feeding (p<0.05), which is significant as protein turnover is especially critical during infancy. Next, we measured the effect of methyl donors on the rates of TM, TS, and RM. The rates of RM and TM were iii reduced by ≈75% in the MD-group (p<0.05), while TS was unchanged. In order to evaluate the effectiveness of individual methyl donors on RM, we 'rescued' a second group of MD-animals with betaine (MD+B), folate (MD+F) or both (MD+FB). The rate of RM and TM increased by ≈2--fold after rescue (p<0.05) and reduced protein breakdown (p<0.05). These studies showed that dietary methyl donors affect neonatal methionine metabolism, which should be considered when defining the dietary requirements of methionine during development.iv

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Methionine kinetics in adult men: effects of dietary betaine onl-[2H3-methyl-1 -13C]methionine1–3

Cited by 56 publications

References 34 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

Cystathionine β-synthase deficiency: Effects of betaine supplementation after methionine restriction in B6-nonresponsive homocystinuria

The effects of dietary methyl donors on methionine partitioning in the neonatal piglet

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