TREHALOSE-6-PHOSPHATE, A NEW REGULATOR OF YEAST GLYCOLYSIS THAT INHIBITS HEXOKINASES

Trehalose-6-phosphate (P) competitively inhibited the hexokinases from Saccharomyces cerevisiae. The strongest inhibition was observed upon hexokinase II, with a K(i) of 40 muM, while in the case of hexokinase I the K(i) was 200 muM. Glucokinase was not inhibited by trehalose-6-P up to 5 mM. This inhibition appears to have physiological significanc e, since the intracellular levels of trehalose-6-P were about 0.2 mM. Hexokinases from other organisms were also inhibited, while glucokinas es were unaffected. The hexokinase from the yeast, Yarrowia lipolytica , was particularly sensitive to the inhibition by trehalose-6-P: when assayed with 2 mM fructose an apparent K(i) of 5 muM was calculated. T wo S. cerevisiae mutants with abnormal levels of trehalose-6-P exhibit ed defects in glucose metabolism. It is concluded that trehalose-6-P p lays an important role in the regulation of the first steps of yeast g lycolysis, mainly through the inhibition of hexokinase II.