title: Effects of lithium on the activities of phosphofructokinase and phosphoglucomutase and on glucose-1,6-diphosphate levels in rat muscles, brain and liver.
abstract: Incubation of rat diaphragm muscle in the presence of lithium chloride (a drug used widely in the therapy of patients with mental illness), resulted in a sharp decrease in the level of glucose-1,6-diphosphate (Glc-1,6-P2), the powerful regulator of carbohydrate metabolism. This decrease in Glc-1,6-P2, the most potent activator of phosphofructokinase and phosphoglucomutase, was accompanied by a marked reduction in the activities of both enzymes, when assayed in the absence of exogenous Glc-1,6-P2 under conditions in which these enzymes are sensitive to regulation by endogenous Glc-1,6-P2. A decrease in Glc-1,6-P2 and the concomitant reduction in the activities of phosphofructokinase and phosphoglucomutase, were also obtained in the rat gastrocnemius and tibialis anterior muscles, as well as in brain, following Li+ injection. In contrast to its effects in muscles and brain, Li+ did not exert any effect on Glc-1,6-P2 level and on the enzymes' activities in the liver. The marked inhibition of brain and muscles phosphofructokinase (the rate-limiting enzyme in glycolysis) induced by Li+, may play an important role in the mechanism of the therapeutic action of this agent in the manic state.
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives*; D005958:Glucosephosphates / Q000032:analysis*; D008094:Lithium / Q000494:pharmacology*; D008099:Liver / Q000032:analysis / Q000187:drug effects*; D008297:Male; D009132:Muscles / Q000032:analysis / Q000187:drug effects*; D010732:Phosphofructokinase-1 / Q000032:analysis*; D010733:Phosphoglucomutase / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D005958:Glucosephosphates; D019298:Glucose-6-Phosphate; D008094:Lithium; C016473:glucose-1,6-bisphosphate; D010732:Phosphofructokinase-1; D010733:Phosphoglucomutase