Although it is well known that the intestinal tract has a high metabolic ra
te, the substrates that are used to generate the necessary energy remain po
orly established, especially in fed animals. Under fed conditions, the quan
tification of substrate used by the gut is complicated by the fact that pot
ential oxidative precursors are supplied from both the diet and the arteria
l circulation. To circumvent this problem, and to approach the question of
the compounds used to generate ATP in the gut, we combined measurements of
portal nutrient balance with enteral and intravenous infusions of [U-C-13]s
ubstrates. We studied rapidly growing piglets that were consuming diets bas
ed on whole-milk proteins. The results revealed that 95% of the dietary glu
tamate presented to the mucosa was metabolized in first pass and that of th
is, 50% was metabolized to CO2. Dietary glucose was oxidized to a very limi
ted extent, and arterial glutamine supplied no >15% of the CO2 production b
y the portal-drained viscera. Glutamate was the single largest contributor
to intestinal energy generation. The results also suggested that dietary gl
utamate appeared to be a specific precursor for the biosynthesis of glutath
ione, arginine and proline by the small intestinal mucosa. These studies im
ply that dietary glutamate has an important functional role in the gut. Fur
thermore, these functions are apparently different from those of arterial g
lutamine, the substrate that has received the most attention.