The metabolism of malate by cultured rat brain astrocytes

Journal Article · Sat Dec 01 00:00:00 EST 1990 · Neurochemical Research; (United States)

DOI:https://doi.org/10.1007/BF01208582· OSTI ID:5556632

McKenna, M C; Tildon, J T; Couto, R; Stevenson, J H; Caprio, F J ^[1]

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1. Department of Pediatrics, University of Maryland School of Medicine, Baltimore (USA)

Since malate is known to play an important role in a variety of functions in the brain including energy metabolism, the transfer of reducing equivalents and possibly metabolic trafficking between different cell types; a series of biochemical determinations were initiated to evaluate the rate of 14CO2 production from L-(U-14C)malate in rat brain astrocytes. The 14CO2 production from labeled malate was almost totally suppressed by the metabolic inhibitors rotenone and antimycin A suggesting that most of malate metabolism was coupled to the electron transport system. A double reciprocal plot of the 14CO2 production from the metabolism of labeled malate revealed biphasic kinetics with two apparent Km and Vmax values suggesting the presence of more than one mechanism of malate metabolism in these cells. Subsequent experiments were carried out using 0.01 mM and 0.5 mM malate to determine whether the addition of effectors would differentially alter the metabolism of high and low concentrations of malate. Effectors studied included compounds which could be endogenous regulators of malate metabolism and metabolic inhibitors which would provide information regarding the mechanisms regulating malate metabolism. Both lactate and aspartate decreased 14CO2 production from malate equally. However, a number of effectors were identified which selectively altered the metabolism of 0.01 mM malate including aminooxyacetate, furosemide, N-acetylaspartate, oxaloacetate, pyruvate and glucose, but had little or no effect on the metabolism of 0.5 mM malate. In addition, alpha-ketoglutarate and succinate decreased 14CO2 production from 0.01 mM malate much more than from 0.5 mM malate. In contrast, a number of effectors altered the metabolism of 0.5 mM malate more than 0.01 mM. These included methionine sulfoximine, glutamate, malonate, alpha-cyano-4-hydroxycinnamate and ouabain.

• OSTI ID: 5556632
• Journal Information: Neurochemical Research; (United States), Vol. 15:12; ISSN 0364-3190
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
BRAIN
METABOLISM
MALIC ACID
CARBON 14 COMPOUNDS
CARBON DIOXIDE
CELL CULTURES
ELECTRON TRANSFER
NERVE CELLS
RATS
TRACER TECHNIQUES
ANIMAL CELLS
ANIMALS
BODY
CARBON COMPOUNDS
CARBON OXIDES
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CHALCOGENIDES
HYDROXY ACIDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
NERVOUS SYSTEM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
OXIDES
OXYGEN COMPOUNDS
RODENTS
SOMATIC CELLS
VERTEBRATES
550501* - Metabolism- Tracer Techniques