Developmental changes in cholinephosphate cytidylyltransferase activity and microsomal phospholipid fatty acid composition in alveolar type II cells

Abstract

Cholinephosphate cytidylyltransferase is the rate-limiting enzyme in the choline pathway of phosphatidylcholine synthesis in fetal and adult lung. To examine the developmental changes in cytidylyltransferase activity, subcellular fractions were prepared from freshly isolated type II cells from 19 and 21 d gestation fetal rats, newborn (0 h, 3 h, 3-12 h, +1, +2, +7 postnatal day), and adult rats and the fractions assayed for cytidylyltransferase activity. Cytidylyltransferase activity per cell was low during late fetal gestation, but rose rapidly during the first 3 h after birth, predominantly due to an increase in microsomal enzyme activity. Microsomal and cytosolic enzyme specific activity increased 6 and 3.9 fold, respectively, from birth (0 h) to +1 postnatal day. The subcellular distribution of enzyme activity changed from 40% microsomal in fetal type II cells to 85% microsomal at 3-12 h, and 60% in this compartment in adult type II cells. Although evidence suggests that membrane lipid may affect enzyme activity, developmental changes in type II cell membrane phospholipid fatty acid composition have not been previously studied. Capillary gas chromatography analysis of phospholipid fatty acids extracted from microsome fractions revealed a 3-fold increase in both total saturated and unsaturated phospholipid fatty acids from day 19 to day 21 gestation. There was a further 62% increase in total saturated fatty acids during the first postnatal day, concomitant with the peak in microsomal cytidylyltransferase activity.