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.
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 PEMTrs12325817 (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.
Authors: Karen D Corbin; Manal F Abdelmalek; Melanie D Spencer; Kerry-Ann da Costa; Joseph A Galanko; Wei Sha; Ayako Suzuki; Cynthia D Guy; Diana M Cardona; Alfonso Torquati; Anna Mae Diehl; Steven H Zeisel Journal: FASEB J Date: 2013-01-04 Impact factor: 5.191
Authors: Alan Chalil; Alex P Kitson; Juan J Aristizabal Henao; Kristin A Marks; Jason L Elzinga; Daniel M E Lamontagne-Kam; Daniel Chalil; Flavia Badoud; David M Mutch; Ken D Stark Journal: J Lipid Res Date: 2017-11-22 Impact factor: 5.922
Authors: Nick van Wijk; Carol J Watkins; Robert J J Hageman; John C W Sijben; Patrick G H J Kamphuis; Richard J Wurtman; Laus M Broersen Journal: Nutr Metab (Lond) Date: 2012-05-30 Impact factor: 4.169
Authors: Chiara Valtolina; Arie B Vaandrager; Robert P Favier; Joris H Robben; Maidina Tuohetahuntila; Anne Kummeling; Isabelle Jeusette; Jan Rothuizen Journal: BMC Vet Res Date: 2015-11-09 Impact factor: 2.741