Aspartate aminotransferase in synaptic and nonsynaptic mitochondria: Differential effect of compounds that influence transient hetero-enzyme complex (metabolon) formation

McKenna, Mary C.; Hopkins, Irene B.; Lindauer, Steven L.; Bamford, Penelope

doi:10.1016/j.neuint.2005.11.018

Cited by 44 publications

(50 citation statements)

References 53 publications

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“…Of particular importance for the neuronal functions are macroglial cells or astroglia. Although astrocytes do not participate in the interactions between neurons on the millisecond scale, they are fundamental for supporting neurons with energy substrates and neuromediators [41, 63, 67, 68]. The importance of astroglia for the neuronal energy metabolism becomes evident from the distribution of mitochondria in the neurons.…”

Section: Mitochondrial Metabolism and Functions Depend On Localizamentioning

confidence: 99%

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Fatty Acids in Energy Metabolism of the Central Nervous System

Panov

Orynbayeva

Вавилин

et al. 2014

BioMed Research International

150

144

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In this review, we analyze the current hypotheses regarding energy metabolism in the neurons and astroglia. Recently, it was shown that up to 20% of the total brain's energy is provided by mitochondrial oxidation of fatty acids. However, the existing hypotheses consider glucose, or its derivative lactate, as the only main energy substrate for the brain. Astroglia metabolically supports the neurons by providing lactate as a substrate for neuronal mitochondria. In addition, a significant amount of neuromediators, glutamate and GABA, is transported into neurons and also serves as substrates for mitochondria. Thus, neuronal mitochondria may simultaneously oxidize several substrates. Astrocytes have to replenish the pool of neuromediators by synthesis de novo, which requires large amounts of energy. In this review, we made an attempt to reconcile β-oxidation of fatty acids by astrocytic mitochondria with the existing hypothesis on regulation of aerobic glycolysis. We suggest that, under condition of neuronal excitation, both metabolic pathways may exist simultaneously. We provide experimental evidence that isolated neuronal mitochondria may oxidize palmitoyl carnitine in the presence of other mitochondrial substrates. We also suggest that variations in the brain mitochondrial metabolic phenotype may be associated with different mtDNA haplogroups.

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Section: Mitochondrial Metabolism and Functions Depend On Localizamentioning

confidence: 99%

“…Aspartate may be transported into astrocytic cells, where it will be converted by the cytosolic AAT into glutamate and oxaloacetate (OAA) [68]. …”

Section: Brain But Not Astroglial Mitochondria Possesses the Elecmentioning

confidence: 99%

Fatty Acids in Energy Metabolism of the Central Nervous System

Panov

Orynbayeva

Вавилин

et al. 2014

BioMed Research International

150

144

View full text Add to dashboard Cite

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“…This enzyme AST transfers the amino group to or from glutamate to convert keto acids into amino acids [5]. As a result AST catalyzes the reversible transamination of laspartate to oxaloacetate in conjunction with the conversion of a-ketoglutarate to l-glutamate (Reaction 1).…”

Section: Resultsmentioning

confidence: 99%

“…Especially in the early diagnosis of myocardial infarction, monitoring of AST during the first 24 hours helps to gain an inside into the seriousness of the infarction [4]. The enzyme AST has a number of specific roles in astrocytes and neurons in brain [5], so AST concentrations in cerebrospinal fluid is also important to old people, these markers are useful in distinguishing Alzheimers disease from other forms of dementia [6,7]. The ratio of AST to alanine aminotransferase (ALT) is often greater than 2 : 1 in alcoholic hepatitis.…”

Section: Introductionmentioning

confidence: 99%

The Study of a Disposable Reagentless Biosensor for Fast Test of Aspartate Aminotransferase

et al. 2008

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A reagentless biosensor for amperometric measurement of aspartate aminotransferase (AST) has been developed. The three-electrode biosensor was modified with two enzyme membrane with an integrated planar Ag j AgCl reference electrode. With a cellulose membrane containing catalytic substance coated, the reagentless biosensor was used for measurement of serum AST. The optimal sensitive membrane composition and operation conditions were studied. With low polarizing potential (0 V vs. integrated Ag j AgCl) and appropriate substrate concentration (20 mM a-ketoglutarate acid), the response of the biosensor to AST activity was linear over the range of 25 -1000 U/L with good relativity (R ¼ 0.9904 and 0.9823 in standard AST solutions and AST serum respectively) and fast response time (120 s). The biosensor also indicated good stability of more than 90% of its original activity for 60 days stored in 4 8C, and 90% of the activity was retained after a storage period of 15 days at room temperature (25 8C). The biosensor is expected to be used for the diagnosis of heart and liver disease in the future.

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“…In addition, in vitro tracer studies of (U-14 C)-L-glutamate reveal that both aspartate and glutamine are labeled with the synaptosomal ratio being 2:1 in favor of aspartate but the astrocytic fraction being just over 1:1 in favor of glutamine [80]. Enzyme activity studies indicate that Purkinje neurons predominantly express aspartate aminotransferase (AAT), a little glutamine synthetase (GS) and almost no glutamate dehydrogenase (GDH), whereas astrocytes and Bergmann glia strongly express GDH and GS with only a minor amount of AAT [90][91][92][93][94]. Clearly, astrocytes and neurons metabolize glutamate differently.…”

Section: Glutamate Transport and Intracellular Metabolism In Purkinjementioning

confidence: 99%