Evidence of morphology-specific isozymes inCandida albicans

S-Adenosylmethionine (SAM) synthetase of yeast and hyphal-phase cells of the dimorphic fungusCandida albicans was characterized by kinetic analysis and response to inhibitors. The enzyme from yeast-phase cells has a Km of 0.17 mM for methionine, 0.14 mM for ATP, and is inhibited (in vitro) by dimethyl-sulfoxide, methionine sulfone, and methionine sulfoxide. The hyphal-phase SAM synthetase has a Km of 0.06 mM for methionine, 0.02 mM for ATP, and its activity (in vitro) is enhanced by the substances that inhibit the yeast-phase enzyme. These data strongly suggest that isozymes of SAM synthetase are present inC. albicans and that they are possibly morphology specific. In vivo studies revealed that synthesis of the enzyme is repressed by the addition of methionine to the growth medium and that specific activity of the enzyme increases when intracellular SAM levels are lowered. In addition, it was shown that the increase in specific activity seen during yeast hypha morphogenesis and in yeast cells grown in a methionine-free medium involves de novo protein synthesis.