[1-13C; methyl-2H3]methionine kinetics in humans: methionine conservation and cystine sparing

Storch, Kenneth J.; Wagner, David; Burke, John F.; Young, Vernon R.

doi:10.1152/ajpendo.1990.258.5.e790

Cited by 64 publications

(94 citation statements)

References 29 publications

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“…Under conditions of adequate methionine, f40% of homocysteine is remethylated to methionine through the activity of these enzymes (23). Alterations, therefore, in the function of these enzymes could have important effects on DNA methylation, synthesis, and repair.…”

Section: Discussionmentioning

confidence: 99%

MTRandMTRRPolymorphisms, Dietary Intake, and Breast Cancer Risk

Shrubsole

Gao

Cai

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Section: Discussionmentioning

confidence: 99%

MTRandMTRRPolymorphisms, Dietary Intake, and Breast Cancer Risk

Shrubsole

Gao

Cai

et al. 2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…The mϩ1-to-mϩ4 methionine isotopomer (mϩ1-to-mϩ4) ratio in intracellular pools provides a measure of methionine synthesis from homocysteine relative to uptake from the plasma (21). Simply, for a tissue that produces methionine from homocysteine, the mϩ1-to-mϩ4 ratio will exceed that in the plasma.…”

Section: Statisticsmentioning

confidence: 99%

“…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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“…As a clearer picture develops of the role that elevated homocysteine concentrations play in the risk for chronic disease development in humans, it is important not to lose sight of the fundamental importance of this amino acid in serving as the sole source of sulphur for the endogenous synthesis of cysteine. De novo synthesis of cysteine, through the transsulphuration pathway, represents the primary route for the oxidation of the carbon skeleton of methionine, and is therefore an important component in the control of plasma and tissue methionine levels (Blom et al, 1989;Storch et al, 1990;Stipanuk, 2004). Cysteine synthesis, besides being important for providing a substrate for protein synthesis, is crucial for the regulation of the availability of the biological antioxidant glutathione (Hunter and Grimble, 1997), as well as other sulphur-containing compounds (e.g., taurine).…”

Section: Introductionmentioning

confidence: 99%

Impairments in pyridoxine-dependent sulphur amino acid metabolism are highly sensitive to the degree of vitamin B6 deficiency and repletion in the pig

Zhang

Kebreab

Jing

et al. 2009

Animal

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The objectives of the current study included the characterization of the temporal changes in indices of sulphur amino acid metabolism in piglets in response to vitamin B 6 deficiency and repletion with graded levels of pyridoxine hydrochloride. In Experiment 1, 12 piglets (average initial weight 5 5.3 kg; n 5 6 per group) were fed a semi-purified diet containing either 0 (deficiency group) or 3 mg (control group) pyridoxine Á HCl/kg diet, using a pair-feeding design, for 6 weeks. Piglets consuming vitamin B 6 -deficient diets exhibited decreased average daily gains on the 4th week and feed conversion efficiency from the 4th week until the end of the trial ( P , 0.05). Plasma pyridoxal-5 0 -phosphate (PLP), in pigs consuming vitamin B 6 -deficient diets, was significantly lower than controls throughout the experiment ( P , 0.01), reaching a nadir of 14% of the control animals' value by the end of the trial. Indices of sulphur amino acid metabolism, including activities of hepatic cystathionine-b-synthase (CBS), cystathionine-g-lyase (CGL) and serine hydroxymethyltransferase, as well as hepatic-free cysteine concentrations were markedly decreased after 6 weeks of B 6 deficiency ( P , 0.05). Total hepatic mRNA expressions for CBS and CGL were not affected. Concurrently, hepatic-free homocysteine concentrations increased by more than eight-fold ( P , 0.01) at the end of the trial. An examination of plasma total homocysteine and cysteine concentrations revealed significant ( P , 0.05) differences between treatments, with evidence of an abrupt shift in concentrations at 3 weeks post-initiation of dietary treatments (.25-fold increase in homocysteine; halving of cysteine values). At the end of Experiment 1, vitamin B 6 deficiency significantly increased plasma methionine and serine levels, but decreased plasma glycine concentrations ( P , 0.05). In Experiment 2, 20 pigs of 14 days old (initial BW 5 5.0 kg) were subjected to a 4-week vitamin B 6 depletion protocol, based on results obtained in Experiment 1. After the depletion period and assessment of baseline status (four pigs), remaining pigs were allocated to one of four dietary vitamin B 6 repletion treatments: 0.75, 1.5, 2.25 and 3 mg/kg diet as pyridoxine Á HCl (n 5 4 per level) for 14 days. Significant dose-dependent increases in plasma PLP and cysteine, and decreases in homocysteine were observed, and these were sensitive to the duration of repletion. In conclusion, data from the current studies support the use of both plasma PLP and homocysteine as sensitive indices of vitamin B 6 status in the pig. Additionally, the observed patterns of responses in vitamin B 6 -sensitive metabolites are supportive of an inclusion level of 2.25 mg/kg diet, as pyridoxine Á HCl, in diets for young pigs.Keywords: cysteine, homocysteine, pig, sulphur amino acid, vitamin B 6 ImplicationsThe current study has provided a temporal characterization of the impact of B 6 deficiency and subsequent repletion on indices of sulphur amino acid metabolism in young pigs. The use of plasma and h...

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[1-13C; methyl-2H3]methionine kinetics in humans: methionine conservation and cystine sparing

Cited by 64 publications

References 29 publications

MTRandMTRRPolymorphisms, Dietary Intake, and Breast Cancer Risk

MTRandMTRRPolymorphisms, Dietary Intake, and Breast Cancer Risk

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

Impairments in pyridoxine-dependent sulphur amino acid metabolism are highly sensitive to the degree of vitamin B6 deficiency and repletion in the pig

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