Inhibition of foetal pulmonary choline-phosphate cytidylyltransferase under conditions favouring protein phosphorylation.
Choline-phosphate cytidylyltransferase (EC 2.7.7.15) activity from 25- and 29-day-foetal rabbit lungs was inhibited in both the cytosolic and the microsomal fractions by preincubation with MgATP. The inhibition of the cytosolic enzyme was greater when measured with added phosphatidylglycerol (PG) than without (78-89% versus 50-55%), whereas the inhibition of the microsomal enzyme did not exhibit this distinction (66-72% versus 60-70%). When preincubated with the buffer alone, the cytosolic enzyme was activated to a greater extent by added PG than was the microsomal enzyme (13-14-fold versus 2-3-fold). However, after preincubation with MgATP, the cytosolic enzyme was activated to a smaller extent by added PG (3-6-fold). The inhibition of the enzyme by MgATP required a preincubation and was absent when ADP or AMP was substituted for ATP. Moreover, ATP analogues such as adenosine 5'-[beta, gamma-methylene]triphosphate and adenosine 5'-[gamma-thio]triphosphate also failed to inhibit the enzyme when substituted for ATP in the preincubation. The inhibition by MgATP was not affected by including cyclic AMP in the preincubation, but Ca2+ ions alone or plus diacylglycerol in the preincubation increased the inhibition slightly. The inhibition was abolished by including an inhibitor of cyclic-AMP-dependent protein kinase in the preincubation. These observations, taken collectively, point to the inhibition of foetal pulmonary cytidylyltransferase through the phosphorylation of a protein and suggest that this key enzyme in lung surfactant production may be regulated through this mechanism.
D000227:Adenine Nucleotides / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D019916:Choline-Phosphate Cytidylyltransferase; D008168:Lung / Q000196:embryology* / Q000201:enzymology; D009713:Nucleotidyltransferases / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D011817:Rabbits
D000227:Adenine Nucleotides; D011506:Proteins; D000255:Adenosine Triphosphate; D011494:Protein Kinases; D009713:Nucleotidyltransferases; D019916:Choline-Phosphate Cytidylyltransferase