Regulation of Phospholipid Synthesis in Fetal and Adult Lung.

The regulation of phospholipid synthesis by corticosteroids and fatty acids (FA) was studied in fetal and adult rat lung tissue slices by monitoring the changes in incorporation patterns of ('14)C-labelled glucose, glycerol, and acetate in the presence of these compounds. The incorporation of ('14)C into phospholipids (PL), especially phosphatidyl choline (PC) and phosphatidyl glycerol (PG), normally increased from day 19 to day 21 of gestation (term = 22 days). It decreased after birth to adult levels. Numerous changes in ('14)C-glucose and ('14)C-acetate incorporation at 20-days indicated that was a critical point in fetal lung lipid metabolism, and corresponded to the normal appearance of surfactant dipalmitoyl PC. Dexamethasone injections had no effect on lipid synthesis in adult lung, but did cause an early increase in the synthesis of PG, a component of surfactant. There was also a slight drop in fetal FA labelling. Both effects could be related to hormone-induced changes in cAMP levels, and subsequent regulation of lipogenic enzymes. The addition of palmitate, stearate, oleate, or linoleate to the incubation medium decreased the ('14)C-incorporation into fetal and adult lung PL, especially at 20-days. There was no effect on the FA species synthesized. This suggested an overall drop in the rate of de novo FA synthesis. The specific changes in ('14)C-incorporation with FA additions varied with lipid species, and the FA and glycerol portions of each lipid were affected independently. The labelling of diglyceride FA species did not parallel that of triglycerides or PC. This pointed to independent regulation of PL and neutral lipid synthesis, and either separate pools of DG precursors for PL and neutral lipids or the remodelling of PC. FA synthesis enzyme activities were measured in the presence of 0 to 100 (mu)M FACoA. Citrate cleavage enzyme activity was unchanged, and FA synthetase was inhibited at higher FACoA levels due to detergent effects. Acetyl CoA carboxylase (ACC) was inhibited 40-75% by only 10 (mu)M FACoA. ACC from 20-day fetal lung was most easily inhibited, and palmitoyl CoA was the least effective inhibitor at any stage of development. These in vitro studies suggest mechanisms that may help regulate lung PL synthesis in vivo.Ph.D.BiochemistryUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/159469/1/8314370.pd