L-pyroglutamic acid inhibits energy production and lipid synthesis in cerebral cortex of young rats in vitro.
In the present study we investigated the effects of L-pyroglutamic acid (PGA), which predominantly accumulates in the inherited metabolic diseases glutathione synthetase deficiency (GSD) and gamma-glutamylcysteine synthetase deficiency (GCSD), on some in vitro parameters of energy metabolism and lipid biosynthesis. We evaluated the rates of CO2 production and lipid synthesis from [U-14C]acetate, as well as ATP levels and the activities of creatine kinase and of the respiratory chain complexes I-IV in cerebral cortex of young rats in the presence of PGA at final concentrations ranging from 0.5 to 3 mM. PGA significantly reduced brain CO2 production by 50% at the concentrations of 0.5 to 3 mM, lipid biosynthesis by 20% at concentrations of 0.5 to 3 mM and ATP levels by 52% at the concentration of 3 mM. Regarding the enzyme activities, PGA significantly decreased NADH:cytochrome c oxireductase (complex I plus CoQ plus complex III) by 40% at concentrations of 0.5-3.0 mM and cytochrome c oxidase activity by 22-30% at the concentration of 3.0 mM, without affecting the activities of succinate dehydrogenase, succinate:DCPIP oxireductase (complex II), succinate:cytochrome c oxireductase (complex II plus CoQ plus complex III) or creatine kinase. The results strongly indicate that PGA impairs brain energy production. If these effects also occur in humans, it is possible that they may contribute to the neuropathology of patients affected by these diseases.
Silva
A R
AR
Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.
Silva
C G
CG
Ruschel
C
C
Helegda
C
C
Wyse
A T
AT
Wannmacher
C M
CM
Wajner
M
M
Dutra-Filho
C S
CS
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects*; D066298:In Vitro Techniques; D008055:Lipids / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D011761:Pyrrolidonecarboxylic Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D008055:Lipids; D011761:Pyrrolidonecarboxylic Acid