THE ROLE OF GLUTAMINE AND OTHER ALTERNATE SUBSTRATES AS ENERGY-SOURCES IN THE FETAL-RAT LUNG TYPE-II CELL

Glucose has been thought to be the primary substrate for energy metabo lism in the developing lung; however, alternate substrates are used fo r energy metabolism in other organs. To examine the role of alternate substrates in the lung, we measured rates of oxidation of glutamine, g lucose, lactate, and S-hydroxybutyrate in type II pneumocytes isolated from d 19 fetal rat lungs by measuring the production of (CO2)-C-14 f rom labeled substrates. Glutamine had a rate of 24.36 +/- 4.51 nmol (C O2)-C-14 produced/h/mg of protein (mean +/- SEM), whereas lactate had a significantly higher rate, 40.29 +/- 4.42. 3-Hydroxybutyrate had a r ate of 14.91 +/- 1.93. The rate of glucose oxidation was 2.13 +/- 0.36 , significantly lower than that of glutamine. To examine the interacti ons of substrates normally found in the intracellular milieu, we measu red the effect of unlabeled substrates as competitors on labeled subst rate. This identifies multiple metabolic compart ments of energy metab olism. Glucose, but not lactate, inhibited the oxidation of glutamine, suggesting a compartmentation of tricarboxylic acid cycle activity, r ather than simple dilution by glucose. Glucose and lactate had recipro cal inhibition. Our data suggest at least two separate compartments in the type II cells for substrate oxidation, one for glutamine metaboli sm and a second for glucose metabolism. In summary, we have documented that glutamine and other alternate substrates are oxidized preferenti ally over glucose for energy metabolism in the d 19 fetal rat lung typ e II pneumocyte. In addition, we have delineated some of the compartme ntation that occurs within the developing type II cell, which may dete rmine how these substrates are used.