al., 1997; Zeisel et al., 1997). There is an endogenous pathway for the de novo biosynthesis of the choline moiety via the sequential methylation of phosphatidylethanolamine using S-adenosylmethionine as the methyl donor (Bremer and Greenberg, 1961) (see Figure 12-1). Thus, the demand for dietary choline is modified by metabolic methyl-exchange relationships between choline and three nutrients: methionine, folate, and vitamin B₁₂ (lipotropes) (Zeisel and Blusztajn, 1994).

With this type of nutrient interdependence, designation of the essential nature of a nutrient depends on showing that de novo synthesis rates are not adequate to meet the demand for the nutrient when the other nutrients are available in amounts sufficient to sustain normal growth and function. Healthy men with normal folate and vitamin B₁₂ status fed a choline-deficient diet have diminished plasma choline and phosphatidylcholine concentrations and develop liver damage (Zeisel et al., 1991). For these individuals, de novo synthesis of choline was not adequate to meet the demand for

FIGURE 12-1 Choline, folate, and methionine metabolism are closely interrelated. AdoHcy = S-adenosylhomocysteine, AdoMet = S-adenosylmethionine, B₁₂ = vitamin B₁₂, CDP-Choline = cytidine diphosphocholine, PtdEtn = phosphatidylethanolamine, THF = tetrahydrofolate. Reprinted with permission, from Zeisel and Blusztajn (1994). Copyright 1994 by Annual Reviews.