Effects of betaine in a murine model of mild cystathionine-β-synthase deficiency
Cystathionine-β-synthase (CBS) is required for transsulfuration of homocysteine, an amino acid implicated in vascular disease. We studied homocysteine metabolism in mice with mild hyperhomocysteinemia due to a heterozygous disruption of the Cbs gene. Mice were fed diets supplemented with betaine or...
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Veröffentlicht in: | Metabolism, clinical and experimental clinical and experimental, 2004-05, Vol.53 (5), p.594-599 |
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description | Cystathionine-β-synthase (CBS) is required for transsulfuration of homocysteine, an amino acid implicated in vascular disease. We studied homocysteine metabolism in mice with mild hyperhomocysteinemia due to a heterozygous disruption of the
Cbs gene. Mice were fed diets supplemented with betaine or dimethylsulfonioacetate (DMSA); betaine and DMSA provide methyl groups for an alternate pathway of homocysteine metabolism, remethylation by betaine:homocysteine methyltransferase (BHMT). On control diets, heterozygous mice had 50% higher plasma homocysteine than did wild-type mice. Betaine and DMSA had similar effects in both genotype groups: liver betaine increased dramatically, while plasma homocysteine decreased by 40% to 50%. With increasing betaine supplementation, homocysteine decreased by 75%. Plasma homocysteine and BHMT activity both showed a strong negative correlation with liver betaine. Homocysteinemia in mice is sensitive to a disruption of
Cbs and to methyl donor intake. Because betaine leads to a greater flux through BHMT and lowers homocysteine, betaine supplementation may be beneficial in mild hyperhomocysteinemia. |
doi_str_mv | 10.1016/j.metabol.2003.10.033 |
format | Article |
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Cbs gene. Mice were fed diets supplemented with betaine or dimethylsulfonioacetate (DMSA); betaine and DMSA provide methyl groups for an alternate pathway of homocysteine metabolism, remethylation by betaine:homocysteine methyltransferase (BHMT). On control diets, heterozygous mice had 50% higher plasma homocysteine than did wild-type mice. Betaine and DMSA had similar effects in both genotype groups: liver betaine increased dramatically, while plasma homocysteine decreased by 40% to 50%. With increasing betaine supplementation, homocysteine decreased by 75%. Plasma homocysteine and BHMT activity both showed a strong negative correlation with liver betaine. Homocysteinemia in mice is sensitive to a disruption of
Cbs and to methyl donor intake. Because betaine leads to a greater flux through BHMT and lowers homocysteine, betaine supplementation may be beneficial in mild hyperhomocysteinemia.</description><identifier>ISSN: 0026-0495</identifier><identifier>EISSN: 1532-8600</identifier><identifier>DOI: 10.1016/j.metabol.2003.10.033</identifier><identifier>PMID: 15131763</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Animal Feed ; Animals ; Betaine - metabolism ; Betaine - pharmacology ; Betaine-Homocysteine S-Methyltransferase ; Biological and medical sciences ; Choline - metabolism ; Cystathionine beta-Synthase - deficiency ; Cystathionine beta-Synthase - genetics ; Cysteine - blood ; Female ; Heterozygote ; Homocysteine - blood ; Homocysteine - metabolism ; Hyperhomocysteinemia - drug therapy ; Hyperhomocysteinemia - genetics ; Hyperhomocysteinemia - metabolism ; Lipotropic Agents - metabolism ; Lipotropic Agents - pharmacology ; Liver - metabolism ; Male ; Medical sciences ; Metabolic diseases ; Metals (hemochromatosis...) ; Methionine - blood ; Methyltransferases - metabolism ; Mice ; Mice, Inbred C57BL ; Other metabolic disorders ; Regression Analysis ; Serine - blood</subject><ispartof>Metabolism, clinical and experimental, 2004-05, Vol.53 (5), p.594-599</ispartof><rights>2004 Elsevier Inc.</rights><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c391t-e61f5614c69eddc58fd814cf16cbd8fa2c30914fe5af3abee42db09b86465fd3</citedby><cites>FETCH-LOGICAL-c391t-e61f5614c69eddc58fd814cf16cbd8fa2c30914fe5af3abee42db09b86465fd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.metabol.2003.10.033$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15753010$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15131763$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Schwahn, Bernd C</creatorcontrib><creatorcontrib>Wendel, Udo</creatorcontrib><creatorcontrib>Lussier-Cacan, Suzanne</creatorcontrib><creatorcontrib>Mar, Mei-Heng</creatorcontrib><creatorcontrib>Zeisel, Steven H</creatorcontrib><creatorcontrib>Leclerc, Daniel</creatorcontrib><creatorcontrib>Castro, Carmen</creatorcontrib><creatorcontrib>Garrow, Timothy A</creatorcontrib><creatorcontrib>Rozen, Rima</creatorcontrib><title>Effects of betaine in a murine model of mild cystathionine-β-synthase deficiency</title><title>Metabolism, clinical and experimental</title><addtitle>Metabolism</addtitle><description>Cystathionine-β-synthase (CBS) is required for transsulfuration of homocysteine, an amino acid implicated in vascular disease. We studied homocysteine metabolism in mice with mild hyperhomocysteinemia due to a heterozygous disruption of the
Cbs gene. Mice were fed diets supplemented with betaine or dimethylsulfonioacetate (DMSA); betaine and DMSA provide methyl groups for an alternate pathway of homocysteine metabolism, remethylation by betaine:homocysteine methyltransferase (BHMT). On control diets, heterozygous mice had 50% higher plasma homocysteine than did wild-type mice. Betaine and DMSA had similar effects in both genotype groups: liver betaine increased dramatically, while plasma homocysteine decreased by 40% to 50%. With increasing betaine supplementation, homocysteine decreased by 75%. Plasma homocysteine and BHMT activity both showed a strong negative correlation with liver betaine. Homocysteinemia in mice is sensitive to a disruption of
Cbs and to methyl donor intake. Because betaine leads to a greater flux through BHMT and lowers homocysteine, betaine supplementation may be beneficial in mild hyperhomocysteinemia.</description><subject>Animal Feed</subject><subject>Animals</subject><subject>Betaine - metabolism</subject><subject>Betaine - pharmacology</subject><subject>Betaine-Homocysteine S-Methyltransferase</subject><subject>Biological and medical sciences</subject><subject>Choline - metabolism</subject><subject>Cystathionine beta-Synthase - deficiency</subject><subject>Cystathionine beta-Synthase - genetics</subject><subject>Cysteine - blood</subject><subject>Female</subject><subject>Heterozygote</subject><subject>Homocysteine - blood</subject><subject>Homocysteine - metabolism</subject><subject>Hyperhomocysteinemia - drug therapy</subject><subject>Hyperhomocysteinemia - genetics</subject><subject>Hyperhomocysteinemia - metabolism</subject><subject>Lipotropic Agents - metabolism</subject><subject>Lipotropic Agents - pharmacology</subject><subject>Liver - metabolism</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Metabolic diseases</subject><subject>Metals (hemochromatosis...)</subject><subject>Methionine - blood</subject><subject>Methyltransferases - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Other metabolic disorders</subject><subject>Regression Analysis</subject><subject>Serine - blood</subject><issn>0026-0495</issn><issn>1532-8600</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkMtKxDAUQIMoOj4-QelGdx1vmiZtVyLD-ABBhNmHNLnBDH1o0hHmt_wQv8nUKejOVW7uPffBIeScwpwCFdfreYuDqvtmngGwmJsDY3tkRjnL0lIA7JMZQCZSyCt-RI5DWANAUZTikBxRThktBJuRl6W1qIeQ9Dap40DXYeK6RCXtxo9x2xtsxmLrGpPobRjU8Or6LtbSr880bLvhVQVMDFqnHXZ6e0oOrGoCnk3vCVndLVeLh_Tp-f5xcfuUalbRIUVBLRc016JCYzQvrSnjz1Kha1NalWkGFc0tcmWZqhHzzNRQ1aXIBbeGnZCr3dg3379vMAyydUFj06gO-02QBa0oiDyPIN-B2vcheLTyzbtW-a2kIEeVci0nlXJUOaajyth3MS3Y1C2a367JXQQuJ0AFrRrrVadd-MMVnAGFyN3sOIw2Phx6GX5MoXE-qpemd_-c8g0m5ZZZ</recordid><startdate>20040501</startdate><enddate>20040501</enddate><creator>Schwahn, Bernd C</creator><creator>Wendel, Udo</creator><creator>Lussier-Cacan, Suzanne</creator><creator>Mar, Mei-Heng</creator><creator>Zeisel, Steven H</creator><creator>Leclerc, Daniel</creator><creator>Castro, Carmen</creator><creator>Garrow, Timothy A</creator><creator>Rozen, Rima</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20040501</creationdate><title>Effects of betaine in a murine model of mild cystathionine-β-synthase deficiency</title><author>Schwahn, Bernd C ; Wendel, Udo ; Lussier-Cacan, Suzanne ; Mar, Mei-Heng ; Zeisel, Steven H ; Leclerc, Daniel ; Castro, Carmen ; Garrow, Timothy A ; Rozen, Rima</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c391t-e61f5614c69eddc58fd814cf16cbd8fa2c30914fe5af3abee42db09b86465fd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animal Feed</topic><topic>Animals</topic><topic>Betaine - metabolism</topic><topic>Betaine - pharmacology</topic><topic>Betaine-Homocysteine S-Methyltransferase</topic><topic>Biological and medical sciences</topic><topic>Choline - metabolism</topic><topic>Cystathionine beta-Synthase - deficiency</topic><topic>Cystathionine beta-Synthase - genetics</topic><topic>Cysteine - blood</topic><topic>Female</topic><topic>Heterozygote</topic><topic>Homocysteine - blood</topic><topic>Homocysteine - metabolism</topic><topic>Hyperhomocysteinemia - drug therapy</topic><topic>Hyperhomocysteinemia - genetics</topic><topic>Hyperhomocysteinemia - metabolism</topic><topic>Lipotropic Agents - metabolism</topic><topic>Lipotropic Agents - pharmacology</topic><topic>Liver - metabolism</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Metabolic diseases</topic><topic>Metals (hemochromatosis...)</topic><topic>Methionine - blood</topic><topic>Methyltransferases - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Other metabolic disorders</topic><topic>Regression Analysis</topic><topic>Serine - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Schwahn, Bernd C</creatorcontrib><creatorcontrib>Wendel, Udo</creatorcontrib><creatorcontrib>Lussier-Cacan, Suzanne</creatorcontrib><creatorcontrib>Mar, Mei-Heng</creatorcontrib><creatorcontrib>Zeisel, Steven H</creatorcontrib><creatorcontrib>Leclerc, Daniel</creatorcontrib><creatorcontrib>Castro, Carmen</creatorcontrib><creatorcontrib>Garrow, Timothy A</creatorcontrib><creatorcontrib>Rozen, Rima</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Metabolism, clinical and experimental</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Schwahn, Bernd C</au><au>Wendel, Udo</au><au>Lussier-Cacan, Suzanne</au><au>Mar, Mei-Heng</au><au>Zeisel, Steven H</au><au>Leclerc, Daniel</au><au>Castro, Carmen</au><au>Garrow, Timothy A</au><au>Rozen, Rima</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of betaine in a murine model of mild cystathionine-β-synthase deficiency</atitle><jtitle>Metabolism, clinical and experimental</jtitle><addtitle>Metabolism</addtitle><date>2004-05-01</date><risdate>2004</risdate><volume>53</volume><issue>5</issue><spage>594</spage><epage>599</epage><pages>594-599</pages><issn>0026-0495</issn><eissn>1532-8600</eissn><abstract>Cystathionine-β-synthase (CBS) is required for transsulfuration of homocysteine, an amino acid implicated in vascular disease. We studied homocysteine metabolism in mice with mild hyperhomocysteinemia due to a heterozygous disruption of the
Cbs gene. Mice were fed diets supplemented with betaine or dimethylsulfonioacetate (DMSA); betaine and DMSA provide methyl groups for an alternate pathway of homocysteine metabolism, remethylation by betaine:homocysteine methyltransferase (BHMT). On control diets, heterozygous mice had 50% higher plasma homocysteine than did wild-type mice. Betaine and DMSA had similar effects in both genotype groups: liver betaine increased dramatically, while plasma homocysteine decreased by 40% to 50%. With increasing betaine supplementation, homocysteine decreased by 75%. Plasma homocysteine and BHMT activity both showed a strong negative correlation with liver betaine. Homocysteinemia in mice is sensitive to a disruption of
Cbs and to methyl donor intake. Because betaine leads to a greater flux through BHMT and lowers homocysteine, betaine supplementation may be beneficial in mild hyperhomocysteinemia.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>15131763</pmid><doi>10.1016/j.metabol.2003.10.033</doi><tpages>6</tpages></addata></record> |
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subjects | Animal Feed Animals Betaine - metabolism Betaine - pharmacology Betaine-Homocysteine S-Methyltransferase Biological and medical sciences Choline - metabolism Cystathionine beta-Synthase - deficiency Cystathionine beta-Synthase - genetics Cysteine - blood Female Heterozygote Homocysteine - blood Homocysteine - metabolism Hyperhomocysteinemia - drug therapy Hyperhomocysteinemia - genetics Hyperhomocysteinemia - metabolism Lipotropic Agents - metabolism Lipotropic Agents - pharmacology Liver - metabolism Male Medical sciences Metabolic diseases Metals (hemochromatosis...) Methionine - blood Methyltransferases - metabolism Mice Mice, Inbred C57BL Other metabolic disorders Regression Analysis Serine - blood |
title | Effects of betaine in a murine model of mild cystathionine-β-synthase deficiency |
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