title: Lactate downregulates the glycolytic enzymes hexokinase and phosphofructokinase in diverse tissues from mice.
abstract: We examined the effects of lactate on the enzymatic activity of hexokinase (HK), phosphofructokinase (PFK) and pyruvate kinase (PK) in various mouse tissues. Our results showed that lactate inhibited PFK activity in all the analyzed tissues. This inhibitory effect was observed in skeletal muscle even in the presence of insulin. Lactate directly inhibited the phosphorylation of PFK tyrosine residues in skeletal muscle, an important mechanism of the enzyme activation. Moreover, lactate indirectly inhibited HK activity, which resulted from its cellular redistribution, here attributed to alterations of HK structure. PK activity was not affected by lactate. The activity of HK and PFK is directly related to glucose metabolism. Thus, it is conceivable that lactate exposure can induce inhibition of glucose consumption in tissues.
authors.affiliation: Laboratório de Enzimologia e Controle do Metabolismo (LabECoM), Departamento de Fármacos, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Tiago C
authors.initials: TC
authors.lastname: Leite
authors.forename: Raquel G
authors.initials: RG
authors.lastname: Coelho
authors.forename: Daniel
authors.initials: D
authors.lastname: Da Silva
authors.forename: Wagner S
authors.initials: WS
authors.lastname: Coelho
authors.forename: Monica M
authors.initials: MM
authors.lastname: Marinho-Carvalho
authors.forename: Mauro
authors.initials: M
authors.lastname: Sola-Penna
mesh_terms: D000818:Animals; D015153:Blotting, Western; D015536:Down-Regulation / Q000187:drug effects*; D005635:Fructosediphosphates / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006593:Hexokinase / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D019344:Lactic Acid / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D025221:Phosphofructokinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D014443:Tyrosine / Q000378:metabolism
chemical_list: D005635:Fructosediphosphates; D007004:Hypoglycemic Agents; D007328:Insulin; D019344:Lactic Acid; D014443:Tyrosine; C027652:fructose 2,6-diphosphate; D025221:Phosphofructokinases; D006593:Hexokinase