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 [lns(1,4,5)P-3] was exa mined in yeast cells and germ tubes of Candida albicans. Methods have been developed for analysis of the two key metabolic enzymes, lns(1,4, 5)P-3 kinase and phosphatase. ATP-dependent lns(1,4,5)P-3 kinase activ ity was detected predominantly in the soluble fraction of cell extract s and exhibited a K-m of approximately 9 mu M. The apparent K-m of lns (1,4,5)P-3 phosphatase for lns(1,4,5)P, was approximately 480 mu M. Th e slow rate of dephosphorylation of lns(1,4,5)P, to inositol bisphosph ate suggests a lower importance of the phosphatase within cells compar ed to the kinase. Since both yeast cells and germ tubes of C. albicans rapidly phosphorylated lns(1,4,5)P-3 to inositol tetrakisphosphate an d inositol penta/hexakisphosphate, it is suggested that lns(1,4,5)P-3 has an important role as a precursor for production of these compounds . A sustained increase in cellular lns(1,4,5)P-3 levels was observed d uring germ tube formation and, prior to the onset of germination betwe en 1 and 2 h incubation, the lns(1,4,5)P-3 content increased up to eig htfold. Transient increases in the level of lns(1,4,5)P, were also obs erved during yeast-like growth of C. albicans. The possible role and r elative importance of lns(1,4,5)P-3 as a precursor for inositol polyph osphates and in signal transduction involving Ca2+ release from intern al stores is discussed.