Metabolism of Malonic Acid in Rat Brain After Intracerebral Injection

Abstract

Abstract— Labeled malonic acid ([1‐14C] and [2‐14C]) was injected into the left cerebral hemisphere of anesthetized adult rats in order to determine the metabolic fate of this dicarboxylic acid in central nervous tissue. The animals were allowed to survive for 2, 5, 10. 15 or 30min. Blood was sampled from the torcular during the experimental period and labeled metabolites were extracted from the brain after intracardiac perfusion. There was a very rapid efflux of unreacted malonate in the cerebral venous blood. Labeled CO2 was recovered from the venous blood and the respired air after the injection of [1‐14C]malonate but not after [2‐14C]malonate. The tissue extracts prepared from the brain showed only minimal labeling of fatty acids and sterols. Much higher radioactivity was present in glutamate, glutamine, aspartate, and GABA. The relative specific activities (RSA) of glutamine never rose above 1.00. Aspartate was labeled very rapidly and revealed evidence of 14CO2 fixation in addition to labeling through the Krebs cycle. GABA revealed higher RSA after [1‐14C]malonate than after [2‐14C]malonate. Sequential degradations of glutamate and aspartate proved that labeling of these amino acids occurred from [1‐14C] acetyl‐CoA and [2‐14C] acetyl‐CoA, respectively, via the Krebs cycle. Malonate activation and malonyl‐CoA decarboxylation in vivo were similar to experiments with isolated mitochondria. However, labeled malonate was not incorporated into the amino acids of free mitochondria. The results were compared to data obtained after intracerebral injection of [1‐14C]acetate and [2‐14C]acetate.

Malonate Metabolism: Biochemistry, Molecular Biology, Physiology, and Industrial Application

“…On the other hand, Koeppen and his co-workers studied malonate-related enzymes in the developing rat brain. They indicated that malonate may be involved in the brain development (Koeppen et al, 1974;Mitzen et al, 1976;Koeppen, et al, 1978). This review describes malonate metabolism in view of the biochemical discovery of enzymes that are related to metabolism, characterization of operons encoding malonate-metabolizing enzymes, physiological significance of mutants knocked-out key enzyme, and industrial application of the malonate metabolism.…”

Malonate Decarboxylase in Bacteria and Its Application for Determination of Intracellular Acyl-CoA Thioesters

“…In leaf and root tissue of young soybean, malonate is present in high concentrations and is the predominant acid, but the metabolite does not accumulate as the dead-end product of a metabolic pathway 81,82) . Also, malonate is observed in rat brain and participates in development 47,48,60,61,71) . In both cases, it is likely that malonate is derived from malonylCoA produced by acetyl-CoA carboxylase.…”

Biosynthesis of very long chain fatty acids by the sciatic nerve of the rabbit

“…Their biosynthesis has been studied in brain subfractions [23-291. 336 Although the occurrence of very long chain fatty acids has been demonstrated in the peripheral nervous system [7,22,30 -321, their origin or the conditions of their formation have not been examined so far [33].…”