Re. Fox et al., THE ROLE OF GLUTAMINE AND OTHER ALTERNATE SUBSTRATES AS ENERGY-SOURCES IN THE FETAL-RAT LUNG TYPE-II CELL, Pediatric research, 40(1), 1996, pp. 135-141
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.