Effects of methylmalonate and propionate on [3H]glutamate binding, adenylate cyclase activity and lipid synthesis in rat cerebral cortex.
The effects of methylmalonic (MMA) and propionic acid (PPA), metabolites that accumulate in methylmalonic and propionic acidemia respectively, on [3H]glutamate binding, adenylate cyclase activity and [U-14C]acetate incorporation into lipids were investigated in rat cerebral cortex. Neither acid effected [3H]glutamate binding, regardless of the presence of sodium in the incubation medium. Also, the acids had no effect on basal or GMP-PNP-stimulated adenylate cyclase activity. These results suggest that MMA and PPA do not interact with glutamate binding sites and have no effect on basal or guanine nucleotide-stimulated adenylate cyclase activity. In contrast, [U-14C]acetate incorporation into brain lipids was significantly blocked by both acids, the effects being more pronounced with PPA, indicating an inhibition of brain lipid biosynthesis caused by MMA and PPA. These results may explain at least in part the hypomyelinization and/or demyelinization characteristic of patients affected by methylmalonic acidemia and propionic acidemia.
de Mello
C F
CF
Departamento de Química, Universidade Federal de Santa Maria, RS, Brasil.
Rubin
M A
MA
Coelho
J
J
Wajner
M
M
Souza
D O
DO
D000085:Acetates / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D008055:Lipids / Q000096:biosynthesis*; D008297:Male; D008764:Methylmalonic Acid / Q000494:pharmacology*; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000378:metabolism; D014316:Tritium
D000085:Acetates; D008055:Lipids; D011422:Propionates; D014316:Tritium; D006165:Guanylyl Imidodiphosphate; D018698:Glutamic Acid; D008764:Methylmalonic Acid; D012964:Sodium; D000262:Adenylyl Cyclases; C029658:propionic acid