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CTP:phosphocholine cytidylyltransferase (CT) catalyses a rate regulatory step in the de novo synthesis of surfactant phosphatidylcholine (PC). We have previously shown that CT activity increases during late gestation in alveolar type II cells, and that this increase is most pronounced in microsomes. As it is known that CT is activated by lipids, we investigated the lipid activation of CT in fetal type II cells during late gestation. The degree of activation of cytosolic CT by PC/oleic acid (OA) (1:1 molar ratio) vesicles was gestation-dependent (a 3-fold stimulation on d 18 and a 1.5-fold stimulation on d 21). In contrast, microsomal CT activation by PC/OA vesicles (1.5-fold) remained constant with advancing gestation. Lipids extracted from microsomes of fetal type II cells of different gestational ages (d 18-21) did not differ in their ability to activate either cytosolic CT of d 18 or 21 fetal type II cells, purified CT from adult lung, or delipidated purified CT. In contrast, lipids extracted from cytosol of fetal type II cells of different gestational ages (d 18 and 21) differed in their ability to activate either delipidated cytosolic CT of fetal type II cells, or delipidated purified CT from adult lung. Day 21 cytosolic lipids activated CT more than d 18 cytosolic lipids. Both cytosolic and purified CT, when delipidated by acetone/butanol extraction, showed reduced activities. Several lipids were tested for their ability to activate cytosolic CT. Acidic phospholipids and the mixture of PC/OA (1:1) were the strongest stimulators of cytosolic CT activity. We conclude that cytosolic but not microsomal lipids are involved in the developmental activation of cytosolic CT in fetal type II cells at late gestation.

Regulation of CTP: Phosphocholine Cytidylyltransferase by Cytosolic Lipids in Rat Type II Pneumocytes during Development