Role of cytidine triphosphate and cytidine diphosphate in promoting inositol entry into microsomal phosphatidylinositol.
The Mn2+ activated incorporation of myo-inositol-3H into subfractions of phosphatidylinositol in rat liver microsomes was studied in the presence and absence of cytidine triphosphate or cytidine diphosphate choline using phosphate buffer. The distribution of labeled inositol among molecular species of microsomal phosphatidylinositol was also investigated in vivo. In other experiments, the release of radioactivity from microsomes labeled with inositol-3H in the phospholipid was measured after the addition of Mn2+, unlabeled inositol, and cytidine nucleotide. Similar chase experiments were conducted with microsomes containing phosphatidylcholine-14C or phosphatidylethanolamine-14C. The addition of cytidine triphosphate or cytidine diphosphate choline stimulated the rate of inositol-3H entry into microsomal phosphatidylinositol by 3.5 to 4-fold and the monoenoic plus dienoic, trienoic, tetraenoic, and polyenoic species contained 6-7, 6, 78-81, and 7-9%, of radioactivity, respectively. These latter patterns were very similar to those observed among the corresponding molecular species when the Mn2+ stimulated entry of free inositol into phospholipid was studied in the absence of added cytidine nucleotide. In chase experiments, the release of radioactivity from phospholipid in the presence of cytidine trephosphate or cytidine diphosphate choline was greatly enhanced by the addition of free inositol when microsomes containing phosphatidylinositol-3H, but not phosphatidylcholine-14C or phosphatidylethanolamine-14C, were employed. Therefore, under the present conditions, cytidine triphosphate and cytidine diphosphate choline appear to stimulate the entry of inositol into phosphatidylinositol by enhancing the Mn2+ activated exchange reaction in rat liver microsomes. The results suggest further that phosphatidylinositol is the preferred substrate when this reaction is stimulated by cytidine nucleotide.
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology; D003597:Cytosine Nucleotides / Q000494:pharmacology*; D007294:Inositol / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008345:Manganese / Q000494:pharmacology; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000096:biosynthesis*; D051381:Rats; D013997:Time Factors
D003597:Cytosine Nucleotides; D010716:Phosphatidylinositols; D008345:Manganese; D007294:Inositol; D003566:Cytidine Diphosphate Choline; D008274:Magnesium; D002118:Calcium