Docosahexaenoic acid in plasma phosphatidylcholine may be a potential marker for in vivo phosphatidylethanolamine N-methyltransferase activity in humans
Background: Choline is an essential nutrient for humans, and part of this requirement is met by endogenous synthesis catalyzed by hepatic phosphatidylethanolamine N-methyltransferase (PEMT). PEMT activity is difficult to estimate in humans because it requires a liver biopsy. Previously, we showed th...
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| Veröffentlicht in: | The American journal of clinical nutrition 2011-05, Vol.93 (5), p.968-974 |
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| description | Background: Choline is an essential nutrient for humans, and part of this requirement is met by endogenous synthesis catalyzed by hepatic phosphatidylethanolamine N-methyltransferase (PEMT). PEMT activity is difficult to estimate in humans because it requires a liver biopsy. Previously, we showed that mice that lack functional PEMT have dramatically reduced concentrations of docosahexaenoic acid (DHA; 22:6n−3) in plasma and of liver phosphatidylcholine (PtdCho)—a phospholipid formed by PEMT.
Objective: The objective was to evaluate plasma PtdCho-DHA concentrations as a noninvasive marker of liver PEMT activity in humans.
Design: Plasma PtdCho-DHA concentrations were measured in 72 humans before and after they consumed a low-choline diet, and correlations were analyzed in relation to estrogen status, PEMT polymorphism rs12325817, the ratio of plasma S-adenosylmethionine (AdoMet) to S-adenosylhomocysteine (AdoHcy), and dietary choline intake; all of these factors are associated with changes in liver PEMT activity. PtdCho-DHA and PEMT activity were also measured in human liver specimens.
Results: At baseline, the portion of PtdCho species containing DHA (pmol PtdCho-DHA/nmol PtdCho) was higher in premenopausal women than in men and postmenopausal women (P < 0.01). This ratio was lower in premenopausal women with the rs12325817 polymorphism in the PEMT gene (P < 0.05), and PtdCho-DHA concentration and PEMT activity were lower in human liver samples from women who were homozygous for PEMT rs12325817 (P < 0.05). The ratio of DHA-PtdCho to PtdCho in plasma was directly correlated with the ratio of AdoMet to AdoHcy (P = 0.0001). The portion of PtdCho species containing DHA in plasma was altered in subjects who consumed a low-choline diet.
Conclusion: PtdCho-DHA may be useful as a surrogate marker for in vivo hepatic PEMT activity in humans. This trial was registered at clinicaltrials.gov as NCT00065546. |
| doi_str_mv | 10.3945/ajcn.110.011064 |
| format | Article |
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Objective: The objective was to evaluate plasma PtdCho-DHA concentrations as a noninvasive marker of liver PEMT activity in humans.
Design: Plasma PtdCho-DHA concentrations were measured in 72 humans before and after they consumed a low-choline diet, and correlations were analyzed in relation to estrogen status, PEMT polymorphism rs12325817, the ratio of plasma S-adenosylmethionine (AdoMet) to S-adenosylhomocysteine (AdoHcy), and dietary choline intake; all of these factors are associated with changes in liver PEMT activity. PtdCho-DHA and PEMT activity were also measured in human liver specimens.
Results: At baseline, the portion of PtdCho species containing DHA (pmol PtdCho-DHA/nmol PtdCho) was higher in premenopausal women than in men and postmenopausal women (P < 0.01). This ratio was lower in premenopausal women with the rs12325817 polymorphism in the PEMT gene (P < 0.05), and PtdCho-DHA concentration and PEMT activity were lower in human liver samples from women who were homozygous for PEMT rs12325817 (P < 0.05). The ratio of DHA-PtdCho to PtdCho in plasma was directly correlated with the ratio of AdoMet to AdoHcy (P = 0.0001). The portion of PtdCho species containing DHA in plasma was altered in subjects who consumed a low-choline diet.
Conclusion: PtdCho-DHA may be useful as a surrogate marker for in vivo hepatic PEMT activity in humans. This trial was registered at clinicaltrials.gov as NCT00065546.</description><identifier>ISSN: 0002-9165</identifier><identifier>EISSN: 1938-3207</identifier><identifier>DOI: 10.3945/ajcn.110.011064</identifier><identifier>PMID: 21411618</identifier><identifier>CODEN: AJCNAC</identifier><language>eng</language><publisher>Bethesda, MD: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Aged ; Biological and medical sciences ; Biomarkers ; Biomarkers - blood ; Cholesterol, Dietary - administration & dosage ; Choline - administration & dosage ; Choline Deficiency - blood ; Diet ; Docosahexaenoic Acids - blood ; Docosahexaenoic Acids - metabolism ; Enzymes ; Fatty acids ; Feeding. Feeding behavior ; Female ; Fundamental and applied biological sciences. Psychology ; Genetic Association Studies ; Humans ; Lipids ; Liver ; Liver - enzymology ; Liver - metabolism ; Male ; Menopause ; Middle Aged ; Nutritional Status, Dietary Intake, and Body Composition ; Phosphatidylcholines - blood ; Phosphatidylcholines - metabolism ; Phosphatidylethanolamine N-Methyltransferase - genetics ; Phosphatidylethanolamine N-Methyltransferase - metabolism ; Polymorphism, Single Nucleotide ; Rodents ; S-Adenosylhomocysteine - blood ; S-Adenosylmethionine - blood ; Vertebrates: anatomy and physiology, studies on body, several organs or systems ; Vitamin B ; Young Adult</subject><ispartof>The American journal of clinical nutrition, 2011-05, Vol.93 (5), p.968-974</ispartof><rights>2011 American Society for Nutrition.</rights><rights>2015 INIST-CNRS</rights><rights>Copyright American Society for Clinical Nutrition, Inc. May 1, 2011</rights><rights>2011 American Society for Nutrition 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a452t-59e3910e1a415cde3a000d6ade815c060366c82c47edcdb03999b09518bc7f413</citedby><cites>FETCH-LOGICAL-a452t-59e3910e1a415cde3a000d6ade815c060366c82c47edcdb03999b09518bc7f413</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=25340078$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21411618$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>da Costa, Kerry-Ann</creatorcontrib><creatorcontrib>Sanders, Lisa M</creatorcontrib><creatorcontrib>Fischer, Leslie M</creatorcontrib><creatorcontrib>Zeisel, Steven H</creatorcontrib><title>Docosahexaenoic acid in plasma phosphatidylcholine may be a potential marker for in vivo phosphatidylethanolamine N-methyltransferase activity in humans</title><title>The American journal of clinical nutrition</title><addtitle>Am J Clin Nutr</addtitle><description>Background: Choline is an essential nutrient for humans, and part of this requirement is met by endogenous synthesis catalyzed by hepatic phosphatidylethanolamine N-methyltransferase (PEMT). PEMT activity is difficult to estimate in humans because it requires a liver biopsy. Previously, we showed that mice that lack functional PEMT have dramatically reduced concentrations of docosahexaenoic acid (DHA; 22:6n−3) in plasma and of liver phosphatidylcholine (PtdCho)—a phospholipid formed by PEMT.
Objective: The objective was to evaluate plasma PtdCho-DHA concentrations as a noninvasive marker of liver PEMT activity in humans.
Design: Plasma PtdCho-DHA concentrations were measured in 72 humans before and after they consumed a low-choline diet, and correlations were analyzed in relation to estrogen status, PEMT polymorphism rs12325817, the ratio of plasma S-adenosylmethionine (AdoMet) to S-adenosylhomocysteine (AdoHcy), and dietary choline intake; all of these factors are associated with changes in liver PEMT activity. PtdCho-DHA and PEMT activity were also measured in human liver specimens.
Results: At baseline, the portion of PtdCho species containing DHA (pmol PtdCho-DHA/nmol PtdCho) was higher in premenopausal women than in men and postmenopausal women (P < 0.01). This ratio was lower in premenopausal women with the rs12325817 polymorphism in the PEMT gene (P < 0.05), and PtdCho-DHA concentration and PEMT activity were lower in human liver samples from women who were homozygous for PEMT rs12325817 (P < 0.05). The ratio of DHA-PtdCho to PtdCho in plasma was directly correlated with the ratio of AdoMet to AdoHcy (P = 0.0001). The portion of PtdCho species containing DHA in plasma was altered in subjects who consumed a low-choline diet.
Conclusion: PtdCho-DHA may be useful as a surrogate marker for in vivo hepatic PEMT activity in humans. This trial was registered at clinicaltrials.gov as NCT00065546.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Biomarkers</subject><subject>Biomarkers - blood</subject><subject>Cholesterol, Dietary - administration & dosage</subject><subject>Choline - administration & dosage</subject><subject>Choline Deficiency - blood</subject><subject>Diet</subject><subject>Docosahexaenoic Acids - blood</subject><subject>Docosahexaenoic Acids - metabolism</subject><subject>Enzymes</subject><subject>Fatty acids</subject><subject>Feeding. Feeding behavior</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Genetic Association Studies</subject><subject>Humans</subject><subject>Lipids</subject><subject>Liver</subject><subject>Liver - enzymology</subject><subject>Liver - metabolism</subject><subject>Male</subject><subject>Menopause</subject><subject>Middle Aged</subject><subject>Nutritional Status, Dietary Intake, and Body Composition</subject><subject>Phosphatidylcholines - blood</subject><subject>Phosphatidylcholines - metabolism</subject><subject>Phosphatidylethanolamine N-Methyltransferase - genetics</subject><subject>Phosphatidylethanolamine N-Methyltransferase - metabolism</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Rodents</subject><subject>S-Adenosylhomocysteine - blood</subject><subject>S-Adenosylmethionine - blood</subject><subject>Vertebrates: anatomy and physiology, studies on body, several organs or systems</subject><subject>Vitamin B</subject><subject>Young Adult</subject><issn>0002-9165</issn><issn>1938-3207</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU9v1DAQxSMEokvhzA1FSIhTWjt2vPEFqSp_pQoucLZmnQnx4tiLnY3Yb8LHZaJdCkXiYms8vzea51cUTzm7EFo2l7C14YJTxehQ8l6x4lq0lajZ-n6xYozVleaqOSse5bxljNeyVQ-Ls5pLzhVvV8XP19HGDAP-AAzR2RKs60oXyp2HPEK5G2LeDTC57uDtEL0LWI5wKDdYUjNOGCYHnp7SN0xlH9Oind0c7yhxGiBED-Mi_1iNVB_8lCDkHhNkmmUnN7vpsKiH_UiNx8WDHnzGJ6f7vPjy9s3n6_fVzad3H66vbiqQTT1VjUahOUMOkje2QwFkulPQYUs1U0woZdvayjV2ttswobXeMN3wdmPXveTivHh1nLvbb0ZiyFACb3bJkaeDieDM3U5wg_kaZyPYWqmmpgEvTwNS_L7HPJnRZYveQ8C4z6ZVQtZt0zREPv-H3MZ9CuSOIKk1F7Uk6PII2RRzTtjfrsKZWTI3S-aG4jbHzEnx7G8Ht_zvkAl4cQIgW_A9_bt1-Q_XCMnYeuH0kUP679lhMtk6DBY7l9BOpovuv0v8AjTyzQE</recordid><startdate>20110501</startdate><enddate>20110501</enddate><creator>da Costa, Kerry-Ann</creator><creator>Sanders, Lisa M</creator><creator>Fischer, Leslie M</creator><creator>Zeisel, Steven H</creator><general>Elsevier Inc</general><general>American Society for Nutrition</general><general>American Society for Clinical Nutrition, Inc</general><scope>6I.</scope><scope>AAFTH</scope><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>7QP</scope><scope>7T7</scope><scope>7TS</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20110501</creationdate><title>Docosahexaenoic acid in plasma phosphatidylcholine may be a potential marker for in vivo phosphatidylethanolamine N-methyltransferase activity in humans</title><author>da Costa, Kerry-Ann ; Sanders, Lisa M ; Fischer, Leslie M ; Zeisel, Steven H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a452t-59e3910e1a415cde3a000d6ade815c060366c82c47edcdb03999b09518bc7f413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Biomarkers</topic><topic>Biomarkers - blood</topic><topic>Cholesterol, Dietary - administration & dosage</topic><topic>Choline - administration & dosage</topic><topic>Choline Deficiency - blood</topic><topic>Diet</topic><topic>Docosahexaenoic Acids - blood</topic><topic>Docosahexaenoic Acids - metabolism</topic><topic>Enzymes</topic><topic>Fatty acids</topic><topic>Feeding. Feeding behavior</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Genetic Association Studies</topic><topic>Humans</topic><topic>Lipids</topic><topic>Liver</topic><topic>Liver - enzymology</topic><topic>Liver - metabolism</topic><topic>Male</topic><topic>Menopause</topic><topic>Middle Aged</topic><topic>Nutritional Status, Dietary Intake, and Body Composition</topic><topic>Phosphatidylcholines - blood</topic><topic>Phosphatidylcholines - metabolism</topic><topic>Phosphatidylethanolamine N-Methyltransferase - genetics</topic><topic>Phosphatidylethanolamine N-Methyltransferase - metabolism</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Rodents</topic><topic>S-Adenosylhomocysteine - blood</topic><topic>S-Adenosylmethionine - blood</topic><topic>Vertebrates: anatomy and physiology, studies on body, several organs or systems</topic><topic>Vitamin B</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>da Costa, Kerry-Ann</creatorcontrib><creatorcontrib>Sanders, Lisa M</creatorcontrib><creatorcontrib>Fischer, Leslie M</creatorcontrib><creatorcontrib>Zeisel, Steven H</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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>Calcium & Calcified Tissue Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Physical Education Index</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The American journal of clinical nutrition</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>da Costa, Kerry-Ann</au><au>Sanders, Lisa M</au><au>Fischer, Leslie M</au><au>Zeisel, Steven H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Docosahexaenoic acid in plasma phosphatidylcholine may be a potential marker for in vivo phosphatidylethanolamine N-methyltransferase activity in humans</atitle><jtitle>The American journal of clinical nutrition</jtitle><addtitle>Am J Clin Nutr</addtitle><date>2011-05-01</date><risdate>2011</risdate><volume>93</volume><issue>5</issue><spage>968</spage><epage>974</epage><pages>968-974</pages><issn>0002-9165</issn><eissn>1938-3207</eissn><coden>AJCNAC</coden><abstract>Background: Choline is an essential nutrient for humans, and part of this requirement is met by endogenous synthesis catalyzed by hepatic phosphatidylethanolamine N-methyltransferase (PEMT). PEMT activity is difficult to estimate in humans because it requires a liver biopsy. Previously, we showed that mice that lack functional PEMT have dramatically reduced concentrations of docosahexaenoic acid (DHA; 22:6n−3) in plasma and of liver phosphatidylcholine (PtdCho)—a phospholipid formed by PEMT.
Objective: The objective was to evaluate plasma PtdCho-DHA concentrations as a noninvasive marker of liver PEMT activity in humans.
Design: Plasma PtdCho-DHA concentrations were measured in 72 humans before and after they consumed a low-choline diet, and correlations were analyzed in relation to estrogen status, PEMT polymorphism rs12325817, the ratio of plasma S-adenosylmethionine (AdoMet) to S-adenosylhomocysteine (AdoHcy), and dietary choline intake; all of these factors are associated with changes in liver PEMT activity. PtdCho-DHA and PEMT activity were also measured in human liver specimens.
Results: At baseline, the portion of PtdCho species containing DHA (pmol PtdCho-DHA/nmol PtdCho) was higher in premenopausal women than in men and postmenopausal women (P < 0.01). This ratio was lower in premenopausal women with the rs12325817 polymorphism in the PEMT gene (P < 0.05), and PtdCho-DHA concentration and PEMT activity were lower in human liver samples from women who were homozygous for PEMT rs12325817 (P < 0.05). The ratio of DHA-PtdCho to PtdCho in plasma was directly correlated with the ratio of AdoMet to AdoHcy (P = 0.0001). The portion of PtdCho species containing DHA in plasma was altered in subjects who consumed a low-choline diet.
Conclusion: PtdCho-DHA may be useful as a surrogate marker for in vivo hepatic PEMT activity in humans. This trial was registered at clinicaltrials.gov as NCT00065546.</abstract><cop>Bethesda, MD</cop><pub>Elsevier Inc</pub><pmid>21411618</pmid><doi>10.3945/ajcn.110.011064</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Adult Aged Biological and medical sciences Biomarkers Biomarkers - blood Cholesterol, Dietary - administration & dosage Choline - administration & dosage Choline Deficiency - blood Diet Docosahexaenoic Acids - blood Docosahexaenoic Acids - metabolism Enzymes Fatty acids Feeding. Feeding behavior Female Fundamental and applied biological sciences. Psychology Genetic Association Studies Humans Lipids Liver Liver - enzymology Liver - metabolism Male Menopause Middle Aged Nutritional Status, Dietary Intake, and Body Composition Phosphatidylcholines - blood Phosphatidylcholines - metabolism Phosphatidylethanolamine N-Methyltransferase - genetics Phosphatidylethanolamine N-Methyltransferase - metabolism Polymorphism, Single Nucleotide Rodents S-Adenosylhomocysteine - blood S-Adenosylmethionine - blood Vertebrates: anatomy and physiology, studies on body, several organs or systems Vitamin B Young Adult |
| title | Docosahexaenoic acid in plasma phosphatidylcholine may be a potential marker for in vivo phosphatidylethanolamine N-methyltransferase activity in humans |
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