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Titolo:
REGULATION OF MITOCHONDRIAL AND CYTOSOLIC MALIC ENZYMES FROM CULTUREDRAT-BRAIN ASTROCYTES
Autore:
MCKENNA MC; TILDON JT; STEVENSON JH; HUANG XL; KINGWELL KG;
Indirizzi:
UNIV MARYLAND,SCH MED,DEPT PEDIAT,655 W BALTIMORE ST BALTIMORE MD 21201 UNIV MARYLAND,SCH MED,DEPT BIOL CHEM BALTIMORE MD 21201
Titolo Testata:
Neurochemical research
fascicolo: 12, volume: 20, anno: 1995,
pagine: 1491 - 1501
SICI:
0364-3190(1995)20:12<1491:ROMACM>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
HIPPOCAMPAL SLICE PREPARATION; METHYLENE-DL-ASPARTATE; IMMUNOCYTOCHEMICAL LOCALIZATION; BOVINE BRAIN; C-13 NMR; METABOLISM; NEURONS; MALATE; AMMONIA; LACTATE;
Keywords:
MALATE; MITOCHONDRIAL MALIC ENZYME; CYTOSOLIC MALIC ENZYME; ASTROCYTES; ENERGY METABOLISM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
59
Recensione:
Indirizzi per estratti:
Citazione:
M.C. Mckenna et al., "REGULATION OF MITOCHONDRIAL AND CYTOSOLIC MALIC ENZYMES FROM CULTUREDRAT-BRAIN ASTROCYTES", Neurochemical research, 20(12), 1995, pp. 1491-1501

Abstract

Malate has a number of key roles in the brain, including its functionas a tricarboxylic acid (TCA) cycle intermediate, and as a participant in the malate-aspartate shuttle. In addition, malate is converted topyruvate and CO2 via malic enzyme and may participate in metabolic trafficking between astrocytes and neurons. We have previously demonstrated that malate is metabolized in at least two compartments of TCA cycle activity in astrocytes. Since malic enzyme contributes to the overall regulation of malate metabolism, we determined the activity and kinetics of the mitochondrial and cytosolic forms of this enzyme from cultured astrocytes. Malic enzyme activity measured at 37 degrees C in the presence of 0.5 mM malate was 4.15 +/- 0.47 and 11.61 +/- 0.98 nmol/min/mg protein, in mitochondria and cytosol, respectively (mean +/- SEM, n = 18-19). Malic enzyme activity was also measured in the presenceof several endogenous compounds, which have been shown to alter intracellular malate metabolism in astrocytes, to determine if these compounds affected malic enzyme activity. Lactate inhibited cytosolic malic enzyme by a noncompetitive mechanism, but had no effect on the mitochondrial enzyme. alpha-Ketoglutarate inhibited both cytosolic and mitochondrial malic enzymes by a partial noncompetitive mechanism. Citrate inhibited cytosolic malic enzyme competitively and inhibited mitochondrial malic enzyme noncompetitively at low concentrations of malate, butcompetitively at high concentrations of malate. Both glutamate and aspartate decreased the activity of mitochondrial malic enzyme, but alsoincreased the affinity of the enzyme for malate. The results demonstrate that mitochondrial and cytosolic malic enzymes have different kinetic parameters and are regulated differently by endogenous compounds previously shown to alter malate metabolism in astrocytes. We propose that malic enzyme in brain has an important role in the complete oxidation of anaplerotic compounds for energy.

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Documento generato il 30/03/20 alle ore 18:38:05