title: Docosahexaenoic acid in plasma phosphatidylcholine may be a potential marker for in vivo phosphatidylethanolamine N-methyltransferase activity in humans.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nutrition, School of Public Health and School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Kerry-Ann
authors.initials: KA
authors.lastname: da Costa
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Sanders
authors.forename: Leslie M
authors.initials: LM
authors.lastname: Fischer
authors.forename: Steven H
authors.initials: SH
authors.lastname: Zeisel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D002794:Choline / Q000008:administration & dosage; D002796:Choline Deficiency / Q000097:blood; D004281:Docosahexaenoic Acids / Q000097:blood* / Q000378:metabolism; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008297:Male; D008593:Menopause; D008875:Middle Aged; D010713:Phosphatidylcholines / Q000097:blood* / Q000378:metabolism; D050918:Phosphatidylethanolamine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D012435:S-Adenosylhomocysteine / Q000097:blood; D012436:S-Adenosylmethionine / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D002791:Cholesterol, Dietary; D010713:Phosphatidylcholines; D004281:Docosahexaenoic Acids; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; C494489:PEMT protein, human; D050918:Phosphatidylethanolamine N-Methyltransferase; D002794:Choline