Choline Homocysteine and Folate are Interrelated Nutrients

Choline, methionine, methyltetrahydrofolate (methyl-THF), and vitamins B6 and B12 are closely interconnected at the transmethylation metabolic pathways that form methionine from homocys-teine. Perturbing the metabolism of one of these pathways results in compensatory changes in the others. For example, as noted above, choline can be synthesized de novo using methyl groups derived from methionine (via S-adenosylmethio-nine). Methionine can be formed from homocys-teine using methyl groups from methyl-THF, or using methyl groups from betaine that are derived from choline. Similarly, methyl-THF can be formed from one-carbon units derived from serine or from the methyl groups of choline via dimethylglycine. When animals and humans are deprived of choline, they use more methyl-THF to remethylate homocysteine in the liver and increase dietary folate requirements. Conversely, when they are deprived of folate, they use more methyl groups from choline, increasing the dietary requirement for choline. There is a common polymorphism in the gene for methyltetrahydrofolate reductase that increases dietary requirement for folic acid; 15-30% of humans have this mutation. In mice in which this gene is knocked out, the dietary requirement for choline is increased and they get fatty liver when eating a normal choline diet.

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