The origin of free brain malonate
- Research Service, Veterans Administration Medical Center, Albany, NY (United States)
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.
- OSTI ID:
- 5080407
- Journal Information:
- Neurochemical Research; (United States), Journal Name: Neurochemical Research; (United States) Vol. 16:2; ISSN 0364-3190; ISSN NERED
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMALS
BIOSYNTHESIS
BODY
BRAIN
BUTYRIC ACID
CARBON 14 COMPOUNDS
CARBON COMPOUNDS
CARBOXYLIC ACID SALTS
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CITRATES
DICARBOXYLIC ACIDS
GLUTAMIC ACID
ISOTOPE APPLICATIONS
KETO ACIDS
LABELLED COMPOUNDS
MALONIC ACID
MAMMALS
MONOCARBOXYLIC ACIDS
NERVOUS SYSTEM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PRECURSOR
PYRUVIC ACID
RATS
RODENTS
SYNTHESIS
TRACER TECHNIQUES
VERTEBRATES