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Phosphatidylethanolamine‐methylation is an important consumer of methyl groups in mice and humans
Author(s) -
Stead Lori M,
Jacobs Rene L,
Brosnan John T,
Brosnan Margaret E,
Vance Dennis E
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a89-c
Subject(s) - creatine , phosphatidylethanolamine , phosphatidylcholine , methylation , homocysteine , phospholipid , plasma homocysteine , medicine , biochemistry , chemistry , hyperhomocysteinemia , metabolism , endocrinology , biology , gene , membrane
Biological methylation reactions and homocysteine (Hcy) metabolism are intimately linked. Phosphatidylethanolamine N ‐methyltransferase (PEMT) is an enzyme of phosphatidylcholine (PC) synthesis that is localized predominantly in liver. It catalyses the synthesis of PC from PE, consuming 3 AdoMet molecules in three successive methylations. We hypothesized that the PEMT reaction might contribute significantly to plasma Hcy. Our data show that Pemt −/− mice have plasma Hcy levels ~50% of those in wild type mice. Hepatocytes isolated from Pemt −/− mice secrete ~50% less Hcy. Mice that lack hepatic CTα, however, have significantly elevated plasma Hcy since CTα‐deficient hepatocytes secreted more Hcy than control cells. These data suggest that phospholipid methylation in the liver is a major consumer of AdoMet and a significant source of plasma Hcy. However, our mice data is not consistent early studies in humans which suggest that creatine synthesis accounts for utilization of more than 70% of AdoMet‐derived methyl groups. A re‐examination of human creatine metabolism reveals that, in non‐vegetarians, dietary creatine can account for as much as 50% of daily creatine requirements and, therefore, that estimates of creatine synthesis need to be reduced. We suggest that creatine synthesis is responsible for a much smaller proportion of AdoMet‐derived methyl groups than has been suggested and that phosphatidylcholine synthesis via PEMT is a major consumer of these methyl groups.