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E T Cabacungan

Publications and source records attributed to E T Cabacungan.

3 recordsLinked to original sources

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 metabolism in the developing lung; however, alternate substrates are used for energy metabolism in other organs. To examine the role of alternate substrates in the lung, we measured rates of oxidation of glutamine, glucose, lactate, and 3-hydroxybutyrate in type II pneumocytes isolated from d 19 fetal rat lungs by measuring the production of 14CO2 from labeled substrates. Glutamine had a rate of 24.36 +/- 4.51 nmol 14CO2 produced/ h/mg of protein (mean +/- SEM), whereas lactate had a significantly higher rate, 40.29 +/- 4.42. 3-Hydroxybutyrate had a rate of 14.91 +/- 1.93. The rate of glucose oxidation was 2.13 +/- 0.36, significantly lower than that of glutamine. To examine the interactions of substrates normally found in the intracellular milieu, we measured the effect of unlabeled substrates as competitors on labeled substrate. This identifies multiple metabolic compartments of energy metabolism. Glucose, but not lactate, inhibited the oxidation of glutamine, suggesting a compartmentation of tricarboxylic acid cycle activity, rather than simple dilution by glucose. Glucose and lactate had reciprocal inhibition. Our data suggest at least two separate compartments in the type II cells for substrate oxidation, one for glutamine metabolism and a second for glucose metabolism. In summary, we have documented that glutamine and other alternate substrates are oxidized preferentially over glucose for energy metabolism in the d 19 fetal rat lung type II pneumocyte. In addition, we have delineated some of the compartmentation that occurs within the developing type II cell, which may determine how these substrates are used.

3-Hydroxybutyric Acid↗

Developmentally induced changes in rat lung malic enzyme activities.

To determine lung malic enzyme activity at varying stages of development, both cytosolic and mitochondrial enzyme activities were assayed in rat lungs at various stages from day 16 of fetal life to 2 months of postnatal life by measuring the production of 14CO2 from 14C-malate. Malic enzyme activities were significantly higher in the mitochondrial than in the cytosolic fractions at all ages studied. The mitochondrial malic enzyme activity was significantly higher in canalicular stage (days 19-20) stage of lung development when compared to the glandular stage (days 16-18). The mitochondrial fraction at day 19 exhibited biphasic kinetics: high affinity, Km = 0.45 mmol, Vmax = 10.04 nmol/mg protein/min; and low affinity, Km = 5.48 mmol, Vmax = 56.83 nmol/mg protein/min. The cytosolic malic enzyme activity of all fetal stages (saccular stage [days 16-18], canalicular stage [days 19-20], and glandular stage [days 21-22] were significantly higher when compared to postnatal levels (postnatal days 1-10, adult). In contrast to the mitochondrial fraction, at day 19, the cytosolic fraction showed a single Km of 0.23 mmol, Vmax = 12.32 nmol/mg protein/min. The increased mitochondrial malic enzyme activity during late gestation would suggest that, as we have previously demonstrated, anaplerotic substrates other than glucose, may provide a significant energy source in fetal lung. The increased cytosolic activity in the prenatal phases would suggest that the NADPH provided from malic enzyme is an important contributor to de novo fatty acid synthesis, leading to surfactant synthesis, critical to normal lung development in late gestation.

Age Factors↗