Pathways of palmitate metabolism in the isolated rat lung

Plasma fatty acids represent major precursors of lung lipids. In this study, the pathways of palmitate metabolism were measured in an isolated perfused rat lung. Lungs were ventilated with 5% CO2 in air and perfused with Krebs-Ringer bicarbonate containing 3% serum albumin and 0.25 mM [U-14C] and [9, 10(-3)H] palmitate. Fatty acid utilization was estimated by recovery of radiolabel in products of metabolism. Fourteen percent of a total 14C-fatty-acid utilization of 4.5 mumol fatty acid/100 min/g dry wt. was recovered as 14CO2. Degradation of fatty acid to acetyl CoA was indicated by a 3H2O production that was twice fatty acid oxidation to CO2. The majority of palmitate was recovered in lung phosphatidylcholines with a 14C to 3H ratio of 1.4 accounting for differences between 14C and 3H2O productions. Addition of glucose to the perfusate decreased fatty acid oxidation to CO2 by 32% but had no effect on 14C recovery in phospholipids. Perfusion with the uncoupler of oxidative phosphorylation 2,4-dinitrophenol stimulated fatty acid oxidation twofold but decreased 14C incorporation into lipids. These data together with estimates of fatty acid synthesis based on 3H2O incorporation into lipids, suggested that exogenous fatty acids and glucose both represent sources of carbon for de novo fatty acid synthesis and energy production.