Glutamine metabolism in rat small intestine: synthesis of three-carbon products in isolated enterocytes

Glutamine is a major respiratory fuel for enterocytes but the extent of glutamine decarboxylation in these cells is not certain. The metabolism of differentially labeled L-[¹⁴C]glutamine was studied in enterocytes isolated from fed rats. The results indicate that glutatime undergoes two decarboxylations and yields a three carbon end product. The first decarboxylation is presumably at α-ketoglutarate dehydrogenase but the identity of the second reaction is not clear. The addition of 3-mercaptopicolinate, an inhibitor of phosphoenolpyruvate carboxykinase, was without effect on either the rate of glutamine metabolism or the extent of decarboxylation. Labeled glutamine carbon was recovered in three carbon products primarily as alanine with lesser amounts as lactate. The addition of glucose to the incubation medium did not change the rate of glutamine metabolism, or decarboxylation, but lactate became the major labeled three carbon end product. The results show that the fate, alanine or lactate, of glutamine derived pyruvate in enterocytes depends on the relative rate of flux through pyruvate and indicates that one cytosolic pool of pyruvate exists in these cells. The limited oxidation of glutamine in enterocytes ensures that the gluconeogenic potential of glutamine is conserved within the body.