Immunohistochemical Detection of Betaine–Homocysteine S-Methyltransferase in Human, Pig, and Rat Liver and Kidney

Delgado-Reyes, Cassandra Veronica; Wallig, Matthew A.; Garrow, Timothy A.

doi:10.1006/abbi.2001.2474

Cited by 91 publications

(77 citation statements)

References 15 publications

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“…We isolated mature adipocytes from both GWAT and IWAT from Bhmt Ϫ/Ϫ mice and their littermate controls and measured the rates of [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]oleate incorporation into TAG (for TAG synthesis), into CO 2 (for complete FA oxidation) and acid-soluble metabolites (for incomplete FA oxidation). Mature adipocytes isolated from Bhmt ϩ/ϩ and Bhmt Ϫ/Ϫ GWAT had the same rate of TAG synthesis (Fig.…”

Section: Bhmt Deficiency Resulted In Impaired Tag Synthesis and Enhanmentioning

confidence: 99%

Mouse Betaine-Homocysteine S-Methyltransferase Deficiency Reduces Body Fat via Increasing Energy Expenditure and Impairing Lipid Synthesis and Enhancing Glucose Oxidation in White Adipose Tissue

Teng

Ellis

Coleman

et al. 2012

Journal of Biological Chemistry

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Section: Bhmt Deficiency Resulted In Impaired Tag Synthesis and Enhanmentioning

confidence: 99%

Mouse Betaine-Homocysteine S-Methyltransferase Deficiency Reduces Body Fat via Increasing Energy Expenditure and Impairing Lipid Synthesis and Enhancing Glucose Oxidation in White Adipose Tissue

Teng

Ellis

Coleman

et al. 2012

Journal of Biological Chemistry

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“…259 260 A significant amount of homocysteine metabolism occurs in the kidney [47] and this tissue has 261 been shown to be a major factor under other conditions, such as diabetes, that are characterized 262 by aberrant homocysteine balance [30]. Although the expression of BHMT in the rodent kidney 263 is quite low [48], we found that exercise resulted in a significant increase in renal BHMT activity 264 in the control diet group, as well as the folate-restricted group.…”

mentioning

confidence: 77%

Exercise prevents hyperhomocysteinemia in a dietary folate-restricted mouse model

Neuman¹,

Albright²,

Schalinske³

2013

Nutrition Research

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Hyperhomocysteinemia is a condition that results from altered methyl group metabolism and is associated with numerous pathological conditions. A number of nutritional and hormonal factors have been shown to influence circulating homocysteine concentrations; however, the impact of exercise on homocysteine and methyl group balance is not well understood. Our hypothesis was that exercise represents an effective means to prevent hyperhomocysteinemia in a folate-independent manner. The purpose of this study was to determine the influence of exercise on homocysteine metabolism in a dietary folate-restricted mouse model characterized by moderate hyperhomocysteinemia. Female outbred mice (12 weeks old) were assigned to either a sedentary or free-access wheel exercise group. Following a 4-week acclimation period, half of the mice in each group were provided a folate-restricted diet for 7-weeks prior to euthanasia and tissue collection. As expected, folate-restricted sedentary mice exhibited a 2-fold increase in plasma total homocysteine concentrations; however, exercise completely prevented the increase in circulating homocysteine concentrations. Moreover, exercise reduced plasma homocysteine concentrations 36% within the group fed only the control diet. The prevention of hyperhomocysteinemia by exercise appears, at least in part, to be the result of increased folate-independent homocysteine remethylation owing to a 2-fold increase in renal betaine homocysteine S-methyltransferase. To our knowledge, this is the first report demonstrating the prevention of hyperhomocysteinemia by exercise in a dietary folate-restriction model. Future research will be directed at determining if exercise can have a positive impact on other nutritional, hormonal, and genetic models of hyperhomocysteinemia relevant to humans. Hyperhomocysteinemia is a condition that results from altered methyl group metabolism and is 30 associated with numerous pathological conditions. A number of nutritional and hormonal factors 31 have been shown to influence circulating homocysteine concentrations; however, the impact of 32 exercise on homocysteine and methyl group balance is not well understood. Our hypothesis was 33 that exercise represents an effective means to prevent hyperhomocysteinemia in a folate-34 independent manner. The purpose of this study was to determine the influence of exercise on 35 homocysteine metabolism in a dietary folate-restricted mouse model characterized by moderate 36 hyperhomocysteinemia. Female outbred mice (12 wk old) were assigned to either a sedentary or 37 free-access wheel exercise group. Following a 4-wk acclimation period, half of the mice in each 38 group were provided a folate-restricted diet for 7-wk prior to euthanasia and tissue collection. As 39 expected, folate-restricted sedentary mice exhibited a 2-fold increase in plasma total 40 homocysteine concentrations; however, exercise completely prevented the increase in circulating 41 homocysteine concentrations. Moreover, exercise reduced plasma homocysteine c...

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“…It is possible that decreased PC production is due to an activation of choline oxidase (the enzyme responsible for converting choline to betaine), an inhibition of choline kinase, or a combination of both. To address the role choline oxidation plays in removing choline from the CDP-choline pathway, we repeated the AICAr experiments in a fibroblast cell line (C3H/10T1/2) that contains minimal choline oxidase activity (38). In these cells, [ 3 H]choline incorporation into phosphocholine and PC was reduced by 70% after AICAr treatment (Fig.…”

Section: Aicar Inhibits Pc Biosynthesis Inmentioning

confidence: 99%

Inhibition of Hepatic Phosphatidylcholine Synthesis by 5-Aminoimidazole-4-carboxamide-1-β-4-ribofuranoside Is Independent of AMP-activated Protein Kinase Activation

Jacobs

Lingrell

Dyck

et al. 2007

Journal of Biological Chemistry

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5-Aminoimidazole-4-carboxamide-1-␤-D-ribofuranoside (AICAr), a commonly used indirect activator of AMP-activated protein kinase (AMPK), inhibits phosphatidylcholine (PC) biosynthesis in freshly isolated hepatocytes. In all nucleated mammalian cells, PC is synthesized from choline via the Kennedy (CDP-choline) pathway. The purpose of our study was to provide direct evidence that AMPK regulates phospholipid biosynthesis and to elucidate the mechanism(s) by which AMPK inhibits hepatic PC synthesis. Incubations of hepatocytes with AICAr resulted in a dose-dependent activation of AMPK and inhibition of PC biosynthesis. Surprisingly, adenoviral delivery of constitutively active AMPK did not alter PC biosynthesis. In addition, expression of dominant negative mutants of AMPK was unable to block the AICAr-dependent inhibition of PC biosynthesis, indicating that AICAr was acting independently of AMPK activation. Determination of aqueous intermediates of the CDPcholine pathway indicated that choline kinase, the first enzyme in the pathway, was inhibited by AICAr administration. Flux through the CDP-choline pathway was directly correlated to the level of intracellular ATP concentrations. Therefore, it is possible that inhibition of PC biosynthesis is another process by which the cell can reduce ATP consumption in times of energetic stress. However, unlike cholesterol and triacylglycerol biosynthesis, PC production is not regulated by AMPK. Phosphatidylcholine (PC)4 is quantitatively the most important phospholipid in mammalian membranes, is the primary phospholipid in bile and in plasma lipoproteins, and is a precursor for the synthesis of sphingomyelin and phosphatidylserine. In nucleated cells, PC biosynthesis occurs via the Kennedy (CDP-choline) pathway. Choline kinase (CK), the enzyme catalyzing the first committed step in this pathway, phosphorylates choline to form phosphocholine. Choline kinase is not considered an important site in regulating PC biosynthesis (1-3); however, deletion of the CK␤ isoform results in muscular dystrophy in mice due to lack of PC in muscle (4). CTP:phosphocholine cytidylyltransferase (CT), which catalyzes the rate-limiting conversion of phosphocholine to CDPcholine (1-3), is the most extensively studied enzyme in the Kennedy pathway. CT is found in soluble cell and tissue extracts and bound to membranes. The active form of CT in cells is considered to be membrane-associated, whereas the soluble form is thought to be an inactive reservoir (5, 6). Movement of CT to and from the membrane is linked to cell requirements for PC and is tightly regulated (7-14). The lipid binding domain and the highly phosphorylated C terminus of CT are typically involved in regulating its activity. The last enzyme in the pathway, CDP-choline:1,2-diacylglycerol cholinephosphotransferase, is in excess in cells and thus does not determine the rate of PC biosynthesis. This reaction requires the availability of diacylglycerol, which is synthesized from fatty acids and glycerol.Hepatocytes are unique in that they can a...

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Immunohistochemical Detection of Betaine–Homocysteine S-Methyltransferase in Human, Pig, and Rat Liver and Kidney

Cited by 91 publications

References 15 publications

Mouse Betaine-Homocysteine S-Methyltransferase Deficiency Reduces Body Fat via Increasing Energy Expenditure and Impairing Lipid Synthesis and Enhancing Glucose Oxidation in White Adipose Tissue

Mouse Betaine-Homocysteine S-Methyltransferase Deficiency Reduces Body Fat via Increasing Energy Expenditure and Impairing Lipid Synthesis and Enhancing Glucose Oxidation in White Adipose Tissue

Exercise prevents hyperhomocysteinemia in a dietary folate-restricted mouse model

Inhibition of Hepatic Phosphatidylcholine Synthesis by 5-Aminoimidazole-4-carboxamide-1-β-4-ribofuranoside Is Independent of AMP-activated Protein Kinase Activation

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