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Title: The metabolism of malate by cultured rat brain astrocytes

Abstract

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 metabolismmore » 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.« less

Authors:
; ; ; ;  [1]
  1. Department of Pediatrics, University of Maryland School of Medicine, Baltimore (USA)
Publication Date:
OSTI Identifier:
5556632
Resource Type:
Journal Article
Journal Name:
Neurochemical Research; (United States)
Additional Journal Information:
Journal Volume: 15:12; Journal ID: ISSN 0364-3190
Country of Publication:
United States
Language:
English
Subject:
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

Citation Formats

McKenna, M C, Tildon, J T, Couto, R, Stevenson, J H, and Caprio, F J. The metabolism of malate by cultured rat brain astrocytes. United States: N. p., 1990. Web. doi:10.1007/BF01208582.
McKenna, M C, Tildon, J T, Couto, R, Stevenson, J H, & Caprio, F J. The metabolism of malate by cultured rat brain astrocytes. United States. https://doi.org/10.1007/BF01208582
McKenna, M C, Tildon, J T, Couto, R, Stevenson, J H, and Caprio, F J. 1990. "The metabolism of malate by cultured rat brain astrocytes". United States. https://doi.org/10.1007/BF01208582.
@article{osti_5556632,
title = {The metabolism of malate by cultured rat brain astrocytes},
author = {McKenna, M C and Tildon, J T and Couto, R and Stevenson, J H and Caprio, F J},
abstractNote = {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.},
doi = {10.1007/BF01208582},
url = {https://www.osti.gov/biblio/5556632}, journal = {Neurochemical Research; (United States)},
issn = {0364-3190},
number = ,
volume = 15:12,
place = {United States},
year = {Sat Dec 01 00:00:00 EST 1990},
month = {Sat Dec 01 00:00:00 EST 1990}
}