PMID- 21074528 OWN - NLM STAT- MEDLINE DCOM- 20110315 LR - 20131121 IS - 1873-3468 (Electronic) IS - 0014-5793 (Linking) VI - 585 IP - 1 DP - 2011 Jan 3 TI - Lactate downregulates the glycolytic enzymes hexokinase and phosphofructokinase in diverse tissues from mice. PG - 92-8 LID - 10.1016/j.febslet.2010.11.009 [doi] AB - 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. CI - Copyright (c) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. FAU - Leite, Tiago C AU - Leite TC AD - Laboratorio de Enzimologia e Controle do Metabolismo (LabECoM), Departamento de Farmacos, Faculdade de Farmacia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. FAU - Coelho, Raquel G AU - Coelho RG FAU - Da Silva, Daniel AU - Da Silva D FAU - Coelho, Wagner S AU - Coelho WS FAU - Marinho-Carvalho, Monica M AU - Marinho-Carvalho MM FAU - Sola-Penna, Mauro AU - Sola-Penna M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20101111 PL - England TA - FEBS Lett JT - FEBS letters JID - 0155157 RN - 0 (Fructosediphosphates) RN - 0 (Hypoglycemic Agents) RN - 0 (Insulin) RN - 33X04XA5AT (Lactic Acid) RN - 42HK56048U (Tyrosine) RN - 79082-92-1 (fructose 2,6-diphosphate) RN - EC 2.7.1 - (Phosphofructokinases) RN - EC 2.7.1.1 (Hexokinase) SB - IM MH - Animals MH - Blotting, Western MH - Down-Regulation/*drug effects MH - Fructosediphosphates/pharmacology MH - Heart/drug effects MH - Hexokinase/*metabolism MH - Hypoglycemic Agents/pharmacology MH - Insulin/pharmacology MH - Kidney/drug effects/enzymology MH - Lactic Acid/*pharmacology MH - Liver/drug effects/enzymology MH - Male MH - Mice MH - Muscle, Skeletal/drug effects/enzymology MH - Myocardium/enzymology MH - Phosphofructokinases/*metabolism MH - Phosphorylation/drug effects MH - Tyrosine/metabolism EDAT- 2010/11/16 06:00 MHDA- 2011/03/16 06:00 CRDT- 2010/11/16 06:00 PHST- 2010/08/11 00:00 [received] PHST- 2010/11/04 00:00 [revised] PHST- 2010/11/06 00:00 [accepted] PHST- 2010/11/16 06:00 [entrez] PHST- 2010/11/16 06:00 [pubmed] PHST- 2011/03/16 06:00 [medline] AID - S0014-5793(10)00905-1 [pii] AID - 10.1016/j.febslet.2010.11.009 [doi] PST - ppublish SO - FEBS Lett. 2011 Jan 3;585(1):92-8. doi: 10.1016/j.febslet.2010.11.009. Epub 2010 Nov 11.