Is it time to reevaluate methyl balance in humans?

S-Adenosylmethionine (AdoMet) is the major biological methyl donor. AdoMet's methyl group arises both from the diet (eg, methionine, choline, and betaine) and from de novo synthesis by the process of methylneogenesis. At least 50 AdoMet-dependent methylation reactions have been identified in ma...

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Bibliographic Details
Published in:The American journal of clinical nutrition 2006, Vol.83 (1), p.5-10
Main Authors: Stead, Lori M, Brosnan, John T, Brosnan, Margaret E, Vance, Dennis E, Jacobs, Rene L
Format: Article
Language:English
Subjects:
Animals
biochemical pathways
creatine
Creatine - administration & dosage
Creatine - biosynthesis
Creatine - metabolism
Creatinine - urine
Diet
DNA methylation
Enzymes
homocysteine
human nutrition
Humans
Liver
Methylation
methyltransferases
Mice
Nutrition
phosphatidylcholines
Phosphatidylcholines - biosynthesis
Phosphatidylethanolamine N-Methyltransferase - metabolism
S-Adenosylmethionine - metabolism
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Summary:S-Adenosylmethionine (AdoMet) is the major biological methyl donor. AdoMet's methyl group arises both from the diet (eg, methionine, choline, and betaine) and from de novo synthesis by the process of methylneogenesis. At least 50 AdoMet-dependent methylation reactions have been identified in mammals, and genomic analyses suggest that the final number will be much higher. Such methylation reactions play major roles in biosynthesis, regulation, and detoxification. Creatine synthesis is thought to account for the use of >70% of AdoMet-derived methyl groups in humans. This is not consistent with recent studies in mice, in which the phosphatidylethanolamine methyltransferase gene was deleted (PEMT-/-). Loss of this hepatic enzyme resulted in a 50% decrease in plasma homocysteine, which suggests that it accounts for a major component of whole-body AdoMet utilization. A reexamination of human creatine metabolism showed that dietary creatine can account for as much as 50% of daily creatine requirements in nonvegetarians and, therefore, that estimates of creatine synthesis need to be reduced. We suggest that creatine synthesis is responsible for a smaller proportion of AdoMet-derived methyl groups than has been suggested and that phosphatidylcholine synthesis via phosphatidylethanolamine methyltransferase is a major consumer of these methyl groups.
ISSN:0002-9165
1938-3207
DOI:10.1093/ajcn/83.1.5