Gluconeogenesis and Amino Acid Metasbolism:III. Uptake of Glutamine and Output of Alanine and Ammonia by Non-hepatic Splanchnic Organs of Fasted Rats and Their Metabolic Significance

Amino acid metabolism in non-hepatic splanchnic organs of fasted rats was studied both in vitro and in vivo to determine the roles of glutamine, glutamate, alanine, and ammonia in the amino acid metabolism of these organs and of the whole body. First, arterial-portal vein differences in the plasma concentrations of alanine and ammonia, but not of glutamate, were shown to increase I to 5min after loadingglutamine through the femoral vein, suggesting conversion of the nitrogen of glutamine to that of alanine and ammonia. Second, glutamine was incubated with slices of small intestine and the production of large amounts of glutamate and ammonia, but only a small production of alanine, were observed with a concomitant decrease in glutamine. This result is in sharp contrast to in vivo findings. Third, non-hepatic splanchnic organs were perfused to investigate the problem further by reproducing the in vivo metabolism in vitro. When the organas were perfused without addition of glutamine, the amounts of glutamine in the perfusate and in the intestine did not change appreciably, but alanine and ammonia increased both in the perfusate and in the perfused intestine. The increases in alanine and ammonia in the perfusate were stimulated by the addition of glutamine to the perfusate. Production of ammonia was also demonstrated on perfusing the same organs from germfree rats. These results are largely consistent with in vivo findings and indicate that the nitrogen of glutamine and other amino acids is converted to that of alanine and ammonia in non-hepatic splanchnic organs. In these organs (presumably of the intestine), alanine and ammonia are considered to be "end products" of amino acid metabolism that are conveyed to the liver. This is in contrast to the fact that the " end products" of amino acid metabolism in the kidney are serine and ammonia, while those in peripheral tissues, including the skeletal muscle, skin, and adipose tissue, are alanine and glutamine. Finally, evidence was obtained which suggested that non-hepatic splanchnic organs may play a major role in the trunover of plasma glutamine and in the supply of alanine for hepatic gluconeogenesis in fasted rats.