LUNG CTP CHOLINE-PHOSPHATE CYTIDYLYLTRANSFERASE - ACTIVATION OF CYTOSOLIC SPECIES BY UNSATURATED FATTY-ACID

CTP:choline-phosphate cytidylyltransferase is the principal rate-limit ing enzyme required for surfactant phosphatidylcholine synthesis. We e xamined the in vitro effect of unsaturated fatty acids on the expressi on of the two cytosolic forms of this enzyme in fetal and adult rat lu ng. In the adult, a substantial portion of cytidylyltransferase is exp ressed as the active form (H form). By contrast, the majority of enzym e mass in the fetus is in an inactive form (L form). Oleic acid, or it s esterified derivative, oleoyl-CoA, each stimulated the inactive form (L form) in vitro. However, the addition of oleoyl-CoA directly to th e active form (H form) resulted in a dose-dependent decrease in H-form activity, suggesting feedback inhibition. Further, exposure of the en zyme in fetal lung cytosol to either fatty acid increased the mass of the enzyme, consistent with a shift from the inactive form (L form) to the active species (H form). These observations support a key role fo r unsaturated fatty acids in the developmental regulation of this enzy me.