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 μM, while in the case of hexokinase I the K i was 200 μM. Glucokinase was not inhibited by trehalose‐6‐P up to 5 mM. This inhibition appears to have physiological significance, since the intracellular levels of trehalose‐6‐P were about 0.2 mM. Hexokinases from other organisms were also inhibited, while glucokinases 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 μM was calculated. Two S. cerevisiae mutants with abnormal levels of trehalose‐6‐P exhibited defects in glucose metabolism. It is concluded that trehalose‐6‐P plays an important role in the regulation of the first steps of yeast glycolysis, mainly through the inhibition of hexokinase II.