Quantitative evaluation and regulation of S-adenosylmethionine-dependent transmethylation in sheep tissues

Xue, Gang-Ping; Snoswell, Alan M.

doi:10.1016/0305-0491(86)90055-6

Cited by 13 publications

(10 citation statements)

References 17 publications

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“…Indeed, Xue et al . [20] demonstrated that the liver possesses about 75% of the total‐body capacity for transmethylation, and thus for Hcy production. Chistensen et al .…”

Section: Discussionmentioning

confidence: 99%

Homocysteine‐induced decrease in endothelin‐1 production is initiated at the extracellular level and involves oxidative products

Drunat

Moatti

Paul

et al. 2001

European Journal of Biochemistry

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The increased cardiovascular risk associated with hyperhomocysteinemia has been partly related to homocysteine (Hcy)-induced endothelial cell dysfunction. However, the intra or extracellular starting point of the interaction between Hcy and endothelial cells, leading to cellular dysfunction, has not yet been identified. We investigated the effects of both intracellular and extracellular Hcy accumulation on endothelin-1 (ET-1) synthesis by cultured human endothelial cells. Incubation of cultures with methionine (1.0 mmol : L 21 ) for 2 h induced a slight increase in cellular Hcy content but no change in ET-1 production. Incubation of cells with Hcy (0.2 mmol : L 21 ) led to a significant fall in ET-1 generation, accompanied by a significant increase in cellular Hcy content. Addition of the amino-acid transport system L substrate 2-amino-2-norbornane carboxylic acid had no effect on the Hcy-induced decrease in ET-1 production but significantly inhibited the Hcy-induced increase in the cellular Hcy content. Incubation of cells with a lower Hcy concentration (0.05 mmol : L 21) also reduced ET-1 production without increasing the cellular Hcy content. Co-incubation with extracellular free-radical inhibitors (superoxide dismutase, catalase and mannitol) markedly reduced the effect of Hcy on ET-1 production. Thus, it is extracellular Hcy accumulation that triggers the decrease in ET-1 production by endothelial cells through oxidative products.

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“…Indeed, Xue et al . [20] demonstrated that the liver possesses about 75% of the total‐body capacity for transmethylation, and thus for Hcy production. Chistensen et al .…”

Section: Discussionmentioning

confidence: 99%

Homocysteine‐induced decrease in endothelin‐1 production is initiated at the extracellular level and involves oxidative products

Drunat

Moatti

Paul

et al. 2001

European Journal of Biochemistry

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“…In addition to causing mitochondrial dysfunction, methionine metabolism defects are predicted to alter total cellular methylation potential, as a reduced SAM:SAH ratio and/or elevated SAH inhibit a wide range of cytosolic and nuclear methyltransferases (Chiang et al, 1996). Up to 75% of all mammalian transmethylation reactions occur in the liver (Xue and Snoswell, 1986), and elevated liver SAH has been shown to inhibit the methylation of histones, DNA and lipids in a dose-dependent fashion (Duerre and BriskeAnderson, 1981). Mat1, Pemt and Gnmt knockout mice all develop steatosis, as do human patients with GNMT deficiency (Li et al, 2006;Lu et al, 2001;Luka et al, 2006;Martinez-Chantar et al, 2008;Zhu et al, 2003).…”

Section: Association Of Methionine Metabolism Defects Mitochondrial mentioning

confidence: 99%

TNFα-dependent hepatic steatosis and liver degeneration caused by mutation of zebrafishs-adenosylhomocysteine hydrolase

et al. 2009

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Hepatic steatosis and liver degeneration are prominent features of the zebrafish ducttrip (dtp) mutant phenotype. Positional cloning identified a causative mutation in the gene encoding S-adenosylhomocysteine hydrolase (Ahcy). Reduced Ahcy activity in dtp mutants led to elevated levels of S-adenosylhomocysteine (SAH) and, to a lesser degree, of its metabolic precursor Sadenosylmethionine (SAM). Elevated SAH in dtp larvae was associated with mitochondrial defects and increased expression of tnfa and pparg, an ortholog of the mammalian lipogenic gene. Antisense knockdown of tnfa rescued hepatic steatosis and liver degeneration in dtp larvae, whereas the overexpression of tnfa and the hepatic phenotype were unchanged in dtp larvae reared under germ-free conditions. These data identify an essential role for tnfa in the mutant phenotype and suggest a direct link between SAH-induced methylation defects and TNF expression in human liver disorders associated with elevated TNFα. Although heterozygous dtp larvae had no discernible phenotype, hepatic steatosis was present in heterozygous adult dtp fish and in wildtype adult fish treated with an Ahcy inhibitor. These data argue that AHCY polymorphisms and AHCY inhibitors, which have shown promise in treating autoimmunity and other disorders, may be a risk factor for steatosis, particularly in patients with diabetes, obesity and liver disorders such as hepatitis C infection. Supporting this idea, hepatic injury and steatosis have been noted in patients with recently discovered AHCY mutations.

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“…Under physiological conditions, the SAM methyl group is mainly used to form creatine (Stipanuk, 1986), but can also be channelled to PtdCho, sarcosine, carnitine, and other methylated compounds. In sheep not more than 55 % of the methyl groups of SAM are used for creatine synthesis, which is considerably less than in man (Xue & Snoswell, 1986b). By contrast, the proportion of SAM methyl groups used for choline synthesis is probably considerably greater in sheep than in man, as dietary choline is largely unavailable due to degradation by rumen micro-organisms (Henderson et al 1983;Xue & Snoswell, 1986a,b).…”

Section: Choline As Methyl Donormentioning

confidence: 99%

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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Quantitative evaluation and regulation of S-adenosylmethionine-dependent transmethylation in sheep tissues

Cited by 13 publications

References 17 publications

Homocysteine‐induced decrease in endothelin‐1 production is initiated at the extracellular level and involves oxidative products

Homocysteine‐induced decrease in endothelin‐1 production is initiated at the extracellular level and involves oxidative products

TNFα-dependent hepatic steatosis and liver degeneration caused by mutation of zebrafishs-adenosylhomocysteine hydrolase

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

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