RESUMO
We have investigated the role of carnitine palmitoyltransferase (EC 2.3.1.21) in pulmonar type II pneumocyte, a lung cell responsible for the synthesis of surface active lipids. Adult type II pneumocytes were isolated from rat lung and purified by differential adherence. When these lung cells were incubated with radioactive palmitate, the percentage of radioactivity recovered into dipalmitoylphosphatidylcholine (DPPC), a major surface active lipid, was almost 60% with respect to total phosphatidylcholine (PC) molecular species. Cellular lysates from type II pneumocytes contained detectable amount of carnitine palmitoyltransferase (CPT) activity (1 nmol/min/mg). Most of the CPT activity found in these cells could be inhibited by incubating them for 60 min with 5 microM tetradecylglycidic acid (TDGA), a specific and irreversible CPT inhibitor of the malonyl-CoA sensitive CPT isoform (CPT I). TDGA treatment of adult type II pneumocytes caused a significant reduction in the incorporation of radioactive palmitate into PC, though this effect did not seem to be specific for DPPC. TDGA affected the incorporation of radioactive palmitate at the sn2 rather than the sn1 position of the glycerol backbone of PC. The incorporation of radioactive palmitate into DPPC was also observed when these lung cells were incubated with palmitate-labeled palmitoyl-L-carnitine. Our data suggest that type II pneumocyte CPT may play an important role in remodelling PC fatty acid composition and hence DPPC synthesis.
Assuntos
1,2-Dipalmitoilfosfatidilcolina/biossíntese , Carnitina O-Palmitoiltransferase/metabolismo , Pulmão/citologia , Alvéolos Pulmonares/metabolismo , 1,2-Dipalmitoilfosfatidilcolina/isolamento & purificação , Animais , Células Cultivadas , Cromatografia em Camada Fina , Compostos de Epóxi/antagonistas & inibidores , Compostos de Epóxi/farmacologia , Ácidos Graxos/antagonistas & inibidores , Ácidos Graxos/farmacologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Carnitine and propionyl carnitine both increase production of 14CO2 from [1-14C]pyruvate but only the latter, in a process inhibited by malonate, increases oxygen uptake and 14CO2 evolution from [2-14C]pyruvate. Carnitine increases the rate of formation of acetyl carnitine from pyruvate to a greater extent than propionyl carnitine. These effects of carnitine and propionyl carnitine are not detectable in mitochondria (e.g., rat liver) deficient in carnitine acetyl transferase activity.
