Pancreatic enzymes can liberate choline from dietary phosphatidylcholine, phosphocholine, and glycerophosphocholine (Zeisel and Blusztajn, 1994). The free choline that is formed enters the portal circulation of the liver (Le Kim and Betzing, 1976) whereas phosphatidylcholine may enter via lymph in chylomicrons.

All tissues accumulate choline by diffusion and mediated transport (Zeisel, 1981). A specific carrier mechanism transports free choline across the blood-brain barrier at a rate that is proportional to the serum choline concentration. In the neonate this choline transporter has an especially high capacity (Cornford and Cornford, 1986). The rate at which the liver takes up choline is sufficient to explain the rapid disappearance of choline injected systemically (Zeisel et al., 1980c). The kidney also accumulates choline (Acara and Rennick, 1973). Some of this choline appears in the urine unchanged but most is oxidized within the kidney to form betaine (Rennick et al., 1977).

In the predominant pathway for phosphatidylcholine biosynthesis, choline is phosphorylated, converted to cytidine diphosphocholine, and then converted to phosphatidylcholine (Kennedy and Weiss, 1956; Vance, 1990) (Figure 12-1). In an alternative pathway, phosphatidylethanolamine is sequentially methylated to form phosphatidylcholine by the enzyme phosphatidylethanolamine-N-methyltransferase with S-adenosylmethionine as the methyl donor (Bremer and Greenberg, 1961; Vance and Ridgway, 1988). This is the major (perhaps only) pathway for de novo synthesis of the choline moiety in adult mammals. It is most active in the liver but has been identified in many other tissues (Blusztajn et al., 1979; Crews et al., 1981; Yang et al., 1988). Best estimates of in vivo activity of this enzyme, based on in vitro data, are that 15 to 40 percent of the phosphatidylcholine present in the liver is derived from the phosphatidylethanolamine-N-methyltransferase pathway, with the remainder coming from the cytidine diphosphocholine pathway (Bjornstad and Bremer, 1966; Sundler and Akesson, 1975). No estimates are available as to the relative extent of choline obtained from cell turnover. Dietary intake of phosphatidylcholine is approximately 6 to 10 g/day (Zeisel et al., 1991).

A significant portion of choline is oxidized to form betaine in the liver and kidney (Bianchi and Azzone, 1964; Weinhold and Sanders, 1973). The methyl groups of betaine can be scavenged and reused in single-carbon metabolism (Finkelstein et al., 1982) (see “Nutrient-Nutrient Interactions”).