Choline biosynthesis in sheep. Evidence for extrahepatic synthesis.

1. Choline production by various tissues of the sheep was measured by determining venous and arterial free choline concentrations in blood samples taken from various vessels in conscious multicannulated sheep. 2. Significant production of free choline occurred in the upper and lower body regions, and specifically in the heart, brain and hind-limb muscles of sheep, but there was no significant uptake or output of phosphatidylcholine across these tissues, as determined by arterio-venous differences. 3. In contrast, in the rat there were no significant arterio-venous differences in the concentrations of free choline or phosphatidylcholine across the hind-body. 4. Synthesis of phosphatidylcholine from endogenous phosphatidylethanolamine and S-adenosyl-L-[methyl-14C]methionine was measured in experiments in vitro using microsomal preparations from a variety of sheep and rat tissues. 5. The biosynthetic activity was highest in liver from sheep and rats, although the activity in sheep microsomal preparations was about one-quarter of that in rat microsomal preparations. 6. Microsomal preparations from sheep lung, kidney, gut epithelium, brain, heart and skeletal muscles also showed considerable biosynthetic activity, but in the rat the activity was virtually confined to the liver. 7. Overall, the results show a significant production of choline in extrahepatic tissues of the sheep, with skeletal muscle contributing some 60% of this extrahepatic activity. Thus the extrahepatic production of choline in the sheep, together with the extensive reutilization of bile choline, can explain the maintenance of the large endogenous body pool of choline in this species.