Expression of immunoreactive cytidine 5'-triphosphate: cholinephosphate cytidylyltransferase in developing rat lung.

The principle rate-limiting enzyme required for phosphatidylcholine production is cytidine 5'-triphosphate:cholinephosphate cytidylyltransferase. Two functional forms of cytosolic cytidylyltransferase have been previously identified: an active high-molecular weight multimer (H-form) and a relatively inactive low-molecular-weight species (L-form). In the present study, we examined the maturational changes in enzyme mass in the subcellular fractions of fetal, neonatal, and adult rat lungs. Total enzyme mass, measured by immunoblotting of total cellular lung homogenates, revealed a large amount of immunoreactive enzyme during the fetal and neonatal periods and relatively low levels of enzyme in the adult lung. A similar developmental profile for enzyme mass was noted in the cytosolic and microsomal fractions. Further, in the fetus, the majority of cytosolic enzyme mass was expressed as an inactive form (L-form). Stimulation of fetal cytosol with phosphatidylglycerol converted the enzyme mass from an inactive form (L-form) to an active form (H-form). In the adult, a substantial portion of the cytosolic enzyme mass was expressed as the active species (H-form). These observations suggest that cytidylyltransferase activity early in lung development is accompanied by an increase in enzyme mass, the majority of which exists as an inactive low-molecular-weight species. In contrast, high levels of enzyme activity are maintained in the adult lung, despite relatively low levels of enzyme mass, because a significantly greater portion of the enzyme mass is expressed as an active high-molecular-weight multimer.