title: Creatine kinase activity from rat brain is inhibited by branched-chain amino acids in vitro.
abstract: Maple syrup urine disease (MSUD) is an inherited metabolic disorder biochemically characterized by the accumulation of branched-chain amino acids (BCAAs) and their branched-chain keto acids (BCKAs) in blood and other tissues. Neurological dysfunction is usually present in the affected patients, but the mechanisms of brain damage in this disease are not fully understood. Considering that brain energy metabolism seems to be altered in MSUD, the main objective of this study was to investigate the in vitro effect of BCAAs and BCKAs on creatine kinase activity, a key enzyme of energy homeostasis, in brain cortex of young rats. BCAAs, but not their BCKAs, significantly inhibited creatine kinase activity at concentrations similar to those found in the plasma of MSUD patients (0.5-5 mM). Considering the crucial role creatine kinase plays in energy homeostasis in brain, if this effect also occurs in the brain of MSUD patients, it is possible that inhibition of this enzyme activity may contribute to the brain damage found in this disease.
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Porto Alegre, RS, Brazil.
authors.forename: Carmen
authors.initials: C
authors.lastname: Pilla
authors.forename: Rui Felipe de Oliveira
authors.initials: RF
authors.lastname: Cardozo
authors.forename: Carlos Severo
authors.initials: CS
authors.lastname: Dutra-Filho
authors.forename: Angela Terezinha Souza
authors.initials: AT
authors.lastname: Wyse
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
authors.forename: Clóvis Milton Duval
authors.initials: CM
authors.lastname: Wannmacher
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D003402:Creatine Kinase / Q000037:antagonists & inhibitors*; D004734:Energy Metabolism; D007532:Isoleucine / Q000494:pharmacology; D007700:Kinetics; D007930:Leucine / Q000494:pharmacology; D008375:Maple Syrup Urine Disease / Q000378:metabolism; D051381:Rats; D014633:Valine / Q000494:pharmacology
chemical_list: D000597:Amino Acids, Branched-Chain; D007532:Isoleucine; D003402:Creatine Kinase; D007930:Leucine; D014633:Valine