Biosynthesis of diphosphoinositide in brain.

In 1942, Folch and Woolley (1) reported that inositol is a constituent of brain phospholipids. Folch (2) later isolated from brain a lipid fraction containing 2 atoms of phosphorus per mole of inositol. This material, which was incompletely characterized, was termed brain diphosphoinositide. More recent work by Ballou and his co-workers (3, 4) and by Dawson and Dittmer (5) has shown that there are three distinct inositol-containing phospholipids in brain. These are a monophosphoinositide (I-phosphatidyl L-myo-inositol), a diphosphoinositide (l-phosphatidyl-L-myo-inositol-4-phosphate) and a triphosphoinositide (l-phosphatidyl-L-myo-inositol-4,5-diphosphate) . Interest in the metabolism of the inositol phosphatides has been stimulated by the rapid rate of renewal of these lipids in the brains of living animals (6) and in vitro (7). Recent work has also suggested that the inositol phosphatides may play important phorylation of the monophosphoinositide, although some of the findings of Palmer and Rossiter (16) are not altogether consistent with this hypothesis. In this paper, we wish to describe the finding in brain and other tissues of an enzyme (phosphatidylinositol kinase) which catalyzes the phosphorylation of phosphatidylinositol by ATP to form diphosphoinositide (Equation 2 of Scheme I), and to describe some of its properties. A preliminary report on some aspects of this work has appeared (17).