Docosahexaenoic acid in plasma phosphatidylcholine may be a potential marker for in vivo phosphatidylethanolamine N-methyltransferase activity in humans

• Published in: The American journal of clinical nutrition Vol. 93; no. 5; pp. 968 - 974
• Main Authors: da Costa, Kerry-Ann, Sanders, Lisa M, Fischer, Leslie M, Zeisel, Steven H
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Elsevier Inc 01.05.2011; American Society for Nutrition; American Society for Clinical Nutrition, Inc
• Subjects: administration & dosage; Adolescent; Adult; Aged; Biological and medical sciences; Biomarkers; Biomarkers - blood; biopsy; blood; Cholesterol, Dietary; Cholesterol, Dietary - administration & dosage; choline; Choline - administration & dosage; Choline Deficiency; Choline Deficiency - blood; Diet; docosahexaenoic acid; Docosahexaenoic Acids; Docosahexaenoic Acids - blood; Docosahexaenoic Acids - metabolism; Enzymes; enzymology; estrogens; Fatty acids; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Genetic Association Studies; genetic polymorphism; genetics; Humans; Lipids; Liver; Liver - enzymology; Liver - metabolism; Male; men; Menopause; metabolism; mice; Middle Aged; nutrients; Nutritional Status, Dietary Intake, and Body Composition; Phosphatidylcholines; Phosphatidylcholines - blood; Phosphatidylcholines - metabolism; Phosphatidylethanolamine N-Methyltransferase; Phosphatidylethanolamine N-Methyltransferase - genetics; Phosphatidylethanolamine N-Methyltransferase - metabolism; phospholipids; Polymorphism, Single Nucleotide; Rodents; S-Adenosylhomocysteine; S-Adenosylhomocysteine - blood; S-adenosylmethionine; S-Adenosylmethionine - blood; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vitamin B; women; Young Adult; Human; In vivo; Phosphatidylethanolamine; Phosphatidylcholine; Marker; Docosahexaenoic acid; n-3 fatty acid; Blood plasma
• ISSN: 0002-9165; 1938-3207; 1938-3207
• DOI: 10.3945/ajcn.110.011064

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.