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 Ki of 40 microM, while in the case of hexokinase I the Ki was 200 microM. 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 Ki of 5 microM 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.
Blázquez
M A
MA
Instituto de Investigaciones Biomédicas, CSIC, Madrid, Spain.
Lagunas
R
R
Gancedo
C
C
Gancedo
J M
JM
D001667:Binding, Competitive; D005632:Fructose / Q000378:metabolism; D005941:Glucokinase / Q000037:antagonists & inhibitors; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D006593:Hexokinase / Q000037:antagonists & inhibitors* / Q000235:genetics; D009154:Mutation; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D013403:Sugar Phosphates / Q000235:genetics / Q000494:pharmacology*; D014199:Trehalose / Q000031:analogs & derivatives* / Q000235:genetics / Q000494:pharmacology
D013403:Sugar Phosphates; D005632:Fructose; C082722:trehalose-6-phosphate; D014199:Trehalose; D006593:Hexokinase; D005941:Glucokinase; D005947:Glucose