Neurochemical evidence that glycine induces bioenergetical dysfunction.
Glycine tissue concentrations are increased particularly in nonketotic and ketotic hyperglycinemia, inherited metabolic disorders characterized by severe neurologic damage and brain abnormalities. The present work investigated the in vitro effects of glycine on important parameters of energy metabolism in the brain of young rats. The parameters analyzed were CO2 generated from glucose, acetate and citrate and the activities of the respiratory chain complexes I-IV, of the citric acid cycle enzymes citrate synthase, aconitase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, fumarase and malate dehydrogenase, of creatine kinase and Na+,K+-ATPase. Our results show that glycine significantly reduced CO2 production from acetate, but not from glucose and citrate, reflecting an impairment of the citric acid cycle function. We also observed that the activity of the mitochondrial enzyme citrate synthase was markedly inhibited by glycine, whereas the other activities of the citric acid cycle were not altered. Furthermore, the activity of the respiratory chain was reduced at complexes I-III, II-III and II, as well as of the mitochondrial isoform of creatine kinase and Na+,K+-ATPase. The data indicate that glycine severely impairs brain bioenergetics at the level of energy formation, transfer and utilization. Considering the importance of energy metabolism for brain development and functioning, it is presumed that glycine-induced impairment of brain energy homeostasis may be involved at least in part in the neurological damage found in patients affected by disorders in which brain glycine concentrations are increased.
Busanello
Estela Natacha Brandt
EN
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Moura
Alana Pimentel
AP
Viegas
Carolina Maso
CM
Zanatta
Angela
A
da Costa Ferreira
Gustavo
G
Schuck
Patrícia Fernanda
PF
Wajner
Moacir
M
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology*; D019069:Cell Respiration / Q000187:drug effects / Q000502:physiology; D002952:Citric Acid Cycle / Q000187:drug effects / Q000502:physiology; D003402:Creatine Kinase / Q000187:drug effects / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D005998:Glycine / Q000502:physiology* / Q000633:toxicity; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism; D013347:Subcellular Fractions
D003402:Creatine Kinase; D000254:Sodium-Potassium-Exchanging ATPase; D005998:Glycine