The origin of free brain malonate.
Rat brain contains substantial concentrations of free malonate (192 nmol/g wet weight) but origin and biological importance of the dicarboxylic acid are poorly understood. A dietary source has been excluded. A recently described malonyl-CoA decarboxylase deficiency is associated with malonic aciduria and clinical manifestations, including mental retardation. In an effort to study the metabolic origin of free malonate, several labeled acetyl-CoA precursors were administered by intracerebral injection. [2-14C]pyruvate or [1,5-14C]citrate produced radioactive glutamate but failed to label malonate. In contrast, [1-14C]acetate, [2-14C]acetate, and [1-14C]butyrate were converted to labeled glutamate and malonate after the same route of administration. The intracerebral injection of [1-14C]-beta-alanine as a precursor of malonic semialdehyde and possibly free malonate did not give rise to radioactivity in the dicarboxylate. The labeling pattern of malonic acid is compatible with the reaction sequence: acetyl-CoA----malonyl-CoA----malonate. The final step is thought to occur by transfer of the CoA-group from malonyl-CoA to succinate and/or acetoacetate. Labeling of malonate from acetate is most effective at the age of 7 days when the net concentration of the dicarboxylic acid in rat brain is still very low. At this age, butyrate was a better precursor of malonate than acetate. It is proposed that fatty acid oxidation provides the acetyl-CoA which functions as the precursor of free brain malonate. Compartmentation of malonate biosynthesis is likely because the acetyl-CoA precursors citrate and pyruvate are ineffective.
Research Service, Veterans Administration Medical Center, Albany, N.Y. 12208.
K M
KM
Riley
A C
AC
Dickson
A H
AH
Koeppen
D000085:Acetates / Q000378:metabolism; D019342:Acetic Acid; D000105:Acetyl Coenzyme A / Q000378:metabolism; D000375:Aging / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002087:Butyrates / Q000378:metabolism; D020148:Butyric Acid; D002250:Carbon Radioisotopes; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D007700:Kinetics; D008314:Malonates / Q000378:metabolism*; D008316:Malonyl Coenzyme A / Q000378:metabolism; D051381:Rats
D000085:Acetates; D002087:Butyrates; D002250:Carbon Radioisotopes; D005971:Glutamates; D008314:Malonates; D020148:Butyric Acid; D018698:Glutamic Acid; D008316:Malonyl Coenzyme A; D000105:Acetyl Coenzyme A; C030290:malonic acid; D019342:Acetic Acid