Metabolism of inositol 1,4,5-trisphosphate in Candida albicans: Significance as a precursor of inositol polyphosphates and in signal transduction during the dimorphic transition from yeast cells to germ tubes

The metabolism of inositol 1,4,5-trisphosphate [Ins(1,4,5)P₃] was examined in yeast cells and germ tubes of Candida albicans. Methods have been developed for analysis of the two key metabolic enzymes, Ins(1,4,5)P₃ kinase and phosphatase. ATP-dependent Ins(1,4,5)P₃ kinase activity was detected predominantly in the soluble fraction of cell extracts and exhibited a K(m) of approximately 9 μM. The apparent K(m) of Ins(1,4,5)P₃ phosphatase for Ins(1,4,5)P₃ was approximately 480 μM. The slow rate of dephosphorylation of Ins(1,4,5)P₃ to inositol bisphosphate suggests a lower importance of the phosphatase within cells compared to the kinase. Since both yeast cells and germ tubes of C. albicans rapidly phosphorylated Ins(1,4,5)P₃ to inositol tetrakisphosphate and inositol penta/hexakisphosphate, it is suggested that Ins(1,4,5)P₃ has an important role as a precursor for production of these compounds. A sustained increase in cellular Ins(1,4,5)P₃ levels was observed during germ tube formation and, prior to the onset of germination between 1 and 2 h incubation, the Ins(1,4,5)P₃ content increased up to eightfold. Transient increases in the level of Ins(1,4,5)P₃ were also observed during yeast-like growth of C. albicans. The possible role and relative importance of Ins(1,4,5)P₃ as a precursor for inositol polyphosphates and in signal transduction involving Ca²⁺ release from internal stores is discussed.