Methyl group metabolism in sheep

Snoswell, Alan M.; Xue, Gang-Ping

doi:10.1016/0305-0491(87)90317-8

Cited by 30 publications

(30 citation statements)

References 73 publications

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“…This is an elevated rate of de novo methyl group synthesis from the one-carbon pool, flanked by a low rate of methyl catabolism (due to low activity of choline oxidase). This situation has been demonstrated in adult and in particular lactating sheep (Henderson et al 1983;Robinson et al 1984;Xue & Snoswell, 1986a,b;Snoswell & Xue, 1987) (Table 2). This state is probably an adaptation to the low availability of dietary choline in adult ruminants (Xue & Snoswell, 1986a).…”

Section: Choline As Methyl Donormentioning

confidence: 70%

Comparative mammalian choline metabolism with emphasis on the high-yielding dairy cow

2002

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The present review examines the importance of choline in dairy cow nutrition. Choline is an essential nutrient for mammals when excess methionine and folate are not available in the diet. The requirement for choline can be met by dietary choline and by transmethylation reactions. Two types of functions for choline are known: functions of choline per se; functions as a methyl donor. The two principal methyl donors in animal metabolism are betaine, a metabolite of choline, and S-adenosyl-methionine, a metabolite of methionine. Choline and methionine are interchangeable with regard to their methyl group-furnishing functions. In adult ruminants, choline is extensively degraded in the rumen; for this reason dietary choline contributes insignificantly to the choline body pool and methyl group metabolism is generally conservative with a relatively low rate of methyl catabolism and an elevated rate of de novo synthesis of methyl groups via the tetrahydrofolate system. In dairy ruminants, the dietary availability of choline is still low, but the output of methylated compounds in milk is high, and precursors from the tetrahydrofolate pathway are limiting, especially at the onset of lactation. Therefore choline may be a limiting nutrient for milk production in high-yielding dairy cows.

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Section: Choline As Methyl Donormentioning

confidence: 70%

Comparative mammalian choline metabolism with emphasis on the high-yielding dairy cow

2002

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“…1). Specific activity of this enzyme in sheep hepatocytes is fourfold greater than in the rat (Snoswell & Xue 1987). Transcripts for this vitamin B 12 -dependent enzyme were expressed in all cell types studied in the current experiment, as were transcripts for all the other major folate cycle enzymes including those for dihydrofolate reductase (DHFR; Fig.…”

Section: Folate Metabolismmentioning

confidence: 71%

“…The absence of BHMT transcript expression in the bovine oocyte and pre-implantation embryo is somewhat at odds with a recent report in the human oocyte (Benkhalifa et al 2010), mouse blastocyst (Lee et al 2009) and our previous findings in human ES cells (Steele et al 2005), and may reflect species-specific differences in the importance of this enzyme. It is known, for example, that the specific activity of hepatic BHMT is several fold greater in the rat than in the sheep, and this, together with the relatively low specific activity of hepatic GNMT (EC 2.1.1.20), is thought to be the principal means by which ruminants have adapted to methyl-poor diets (Snoswell & Xue 1987). GNMT has a high K m for SAM and so serves as a benign high-capacity methyltransferase that regulates intra-cellular transmethylation and de novo methyl group synthesis by facilitating the methylation of glycine to sarcosine (Stipanuk 2004).…”

Section: Methionine Cycle Enzymesmentioning

confidence: 99%

Endogenous folates and single-carbon metabolism in the ovarian follicle, oocyte and pre-implantation embryo

Kwong¹,

Adamiak²,

Gwynn³

et al. 2010

Reproduction

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Maternal B-vitamin status at conception can affect fertility and the health of offspring. This study details transcript expression for genes encoding key enzymes in the linked methionine/folate cycles in the bovine oocyte, somatic cells of the ovarian follicle and pre-implantation embryo. Transcripts for all 12 enzymes that were studied and for the two folate receptors (FOLR1 and FOLR2) and reduced folate carrier (SLC19A1) were expressed in liver cells, but transcripts for betaine-homocysteine methyltransferase and methionine adenosyl transferase 1A were absent in all ovarian cells, and transcripts for FOLR2 were absent in embryonic cells. Transcripts for glycine methyltransferase were also absent/weak in cumulus and granulosa cells. The absence of these enzymes could have a profound effect on single-carbon metabolism within the ovary and pre-implantation embryo. Immunocytochemical analysis revealed SLC19A1 protein expression on the plasma and basal-lateral membranes of the pre-implantation embryo. The folate antagonist methotrexate (MTX) enters the cell via SLC19A1, and in the current study, MTX inclusion in bovine/ovine culture media at either 1 or 10 mM from the 1-cell stage inhibited embryo development beyond the 8-cell stage. Hypoxanthine and thymidine (100 mM) increased the proportion of embryos that developed to blastocysts, but the cell number was reduced by 20%. The reduced uptake of [ 35 S] methionine into intra-cellular S-adenosylmethionine and S-adenosylhomocysteine pools, together with reduced uptake of glutamate and tryptophan, was consistent with depleted intra-cellular pools of reduced folates. These data provide an insight into the importance of maternal dietary folate/B-vitamin status during the peri-conceptional period.Reproduction (2010) 139 705-715

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“…In this regard, the effects of gross nutrient or protein deficiencies in maternal diet during pregnancy are well documented (3), although little is known about the effects of specific nutrients or the timing and mechanistic basis of nutrient programming (4). Here we investigated the effects of restricting the supply of specific B group vitamins (i.e., vitamin B 12 and folate) and sulfur amino acids (in particular, methionine) from the diet of adult female sheep from 8 weeks preceding until 6 days after conception, within physiological ranges encountered in both sheep (5) and humans (i.e., within the 5th and 95th percentiles) (6,7). These micronutrients are important intermediates and/or have specific regulatory functions in the linked methionine-folate cycles (5,7).…”

mentioning

confidence: 99%

“…Sheep also lend themselves to the establishment of singleton pregnancies, obviating complications of data interpretation associated with large litters (11). Dietary manipulation of methioninefolate metabolism has been extensively studied in this species (12), assisting diet formulation that, in all other respects, matched their nutrient requirements (13).…”

mentioning

confidence: 99%

DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status

Sinclair

Allegrucci

Singh

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

724

559

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A complex combination of adult health-related disorders can originate from developmental events that occur in utero. The periconceptional period may also be programmable. We report on the effects of restricting the supply of specific B vitamins (i.e., B12 and folate) and methionine, within normal physiological ranges, from the periconceptional diet of mature female sheep. We hypothesized this would lead to epigenetic modifications to DNA methylation in the preovulatory oocyte and/or preimplantation embryo, with long-term health implications for offspring. DNA methylation is a key epigenetic contributor to maintenance of gene silencing that relies on a dietary supply of methyl groups. We observed no effects on pregnancy establishment or birth weight, but this modest early dietary intervention led to adult offspring that were both heavier and fatter, elicited altered immune responses to antigenic challenge, were insulin-resistant, and had elevated blood pressure-effects that were most obvious in males. The altered methylation status of 4% of 1,400 CpG islands examined by restriction landmark genome scanning in the fetal liver revealed compelling evidence of a widespread epigenetic mechanism associated with this nutritionally programmed effect. Intriguingly, more than half of the affected loci were specific to males. The data provide the first evidence that clinically relevant reductions in specific dietary inputs to the methionine/folate cycles during the periconceptional period can lead to widespread epigenetic alterations to DNA methylation in offspring, and modify adult healthrelated phenotypes. E vidence from both epidemiological studies in humans and direct intervention studies in animals indicates that altering key developmental processes in utero can predispose offspring to many late-onset diseases such as dyslipidemia, type II diabetes, and heart disease (1, 2). In this regard, the effects of gross nutrient or protein deficiencies in maternal diet during pregnancy are well documented (3), although little is known about the effects of specific nutrients or the timing and mechanistic basis of nutrient programming (4). Here we investigated the effects of restricting the supply of specific B group vitamins (i.e., vitamin B 12 and folate) and sulfur amino acids (in particular, methionine) from the diet of adult female sheep from 8 weeks preceding until 6 days after conception, within physiological ranges encountered in both sheep (5) and humans (i.e., within the 5th and 95th percentiles) (6, 7). These micronutrients are important intermediates and/or have specific regulatory functions in the linked methionine-folate cycles (5, 7). In rodents, maternal supraphysiological methyl group supply and a low-protein diet (50% control) offered throughout pregnancy altered DNA methylation of candidate genes (agouti, glucocorticoid receptor, and peroxisomal proliferator-activated receptor-␣) (8, 9), but the extent of methylation change in these or more clinically relevant diets is not known. Gametes and preimplantation emb...

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Methyl group metabolism in sheep

Cited by 30 publications

References 73 publications

Comparative mammalian choline metabolism with emphasis on the high-yielding dairy cow

Comparative mammalian choline metabolism with emphasis on the high-yielding dairy cow

Endogenous folates and single-carbon metabolism in the ovarian follicle, oocyte and pre-implantation embryo

DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status

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