Regional and Subcellular Distribution of Aminotransferases in Rat Brain

Benuck, M.; Stern, F.; Lajtha, Ábel

doi:10.1111/j.1471-4159.1972.tb01416.x

Cited by 56 publications

(18 citation statements)

References 27 publications

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“…This aminotransferase catalyzes the reversible interconversion of alanine, α-ketoglutarate, pyruvate and glutamate (Fig.1) and its activity in the brain as well as in cultured brain cells is two orders of magnitude lower than that of aspartate aminotransferase (Benuck et al 1972, Larsson et al 1985, Westergaard et al 1993). The equilibrium constant for alanine aminotransferase (ALAT) is close to unity (Krebs 1953).…”

Section: Enzymatic Reactions Involving Glutamate As Substrate or Productmentioning

confidence: 99%

Glutamate Metabolism in the Brain Focusing on Astrocytes

Schousboe

Scafidi

Bak

et al. 2014

Advances in Neurobiology

293

217

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Metabolism of glutamate, the main excitatory neurotransmitter and precursor of GABA, is exceedingly complex and highly compartmentalized in brain. Maintenance of these neurotransmitter pools is strictly dependent on the de novo synthesis of glutamine in astrocytes which requires both the anaplerotic enzyme pyruvate carboxylase and glutamine synthetase. Glutamate is formed directly from glutamine by deamidation via phosphate activated glutaminase a reaction that also yields ammonia. Glutamate plays key roles linking carbohydrate and amino acid metabolism via the tricarboxylic acid (TCA) cycle, as well as in nitrogen trafficking and ammonia homeostasis in brain. The anatomical specialization of astrocytic endfeet enables these cells to rapidly and efficiently remove neurotransmitters from the synaptic cleft to maintain homeostasis, and to provide glutamine to replenish neurotransmitter pools in both glutamatergic and GABAergic neurons. Since the glutamate-glutamine cycle is an open cycle that actively interfaces with other pathways, the de novo synthesis of glutamine in astrocytes helps to maintain the operation of this cycle. The fine-tuned biochemical specialization of astrocytes allows these cells to respond to subtle changes in neurotransmission by dynamically adjusting their anaplerotic and glycolytic activities, and adjusting the amount of glutamate oxidized for energy relative to direct formation of glutamine, to meet the demands for maintaining neurotransmission. This chapter summarizes the evidence that astrocytes are essential and dynamic partners in both glutamatergic and GABAergic neurotransmission in brain.

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Section: Enzymatic Reactions Involving Glutamate As Substrate or Productmentioning

confidence: 99%

Glutamate Metabolism in the Brain Focusing on Astrocytes

Schousboe

Scafidi

Bak

et al. 2014

Advances in Neurobiology

293

217

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“…The in vivo rate reported here is 3-6% of the in vitro rate of BCAT, 28 j.tmol/100 mg of protein/h (which corresponds to 28 jimol/h/g of wet weight of brain) measured in rat brain homogenate at enzymesaturating concentrations (10 mM) of a-ketoglutarate and leucine (Benuck et al, 1972). BCATC, the predominant isoenzyme in the brain, has.a Km for leucine of 1.25 mM, whereas BCATm has a Km of 0.97 mM.…”

Section: Effects Of Substrate Concentrations On Bcat Activitymentioning

confidence: 99%

Rate of Glutamate Synthesis from Leucine in Rat Brain Measured In Vivo by ¹⁵N NMR

Kanamori

Ross

Kondrat

1998

Journal of Neurochemistry

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Abstract:The rate of glutamate synthesis from leucine by the branched-chain aminotransferase was measured in rat brain in vivo at steady state. The rats were fed exclusively by intravenous infusion of a nutrient solution containing [15N]leucine. The rate of glutamate synthesis from leucine, determined from the rate of increase of brain [15N]glutamate measured by 15N NMR and the 15N enrichments of brain and blood leucine analyzed by gas chromatography-mass spectrometry, was 0.7-1.8 j.tmol/g/ h at a steady-state brain leucine concentration of 0.25 mol/g. A comparison of the observed fractional 15N enrichments of brain leucine (0.42 ±0.03) and glutamate (0.21 ±0.015) showed that leucine provides '-.~50%of glutamate nitrogen under our experimental condition. From the observed rate (0.7-1.8 j.imol/g) and the known Km of the branched-chain aminotransferase for leucine (1.2 mM), the rate of glutamate synthesis from leucine at physiological brain leucine concentration (0.11~mol/ g) was estimated to be 0.35-0.9~mol/g/h, with leucine providing~25% of glutamate nitrogen. The results strongly suggest that plasma leucine from dietary source, transported into the brain, is an important external source of nitrogen for replenishment of brain glutamate in vivo. Implications of the results for treatment of maple-syrup urine disease patients with leucine-restricted diet are discussed. Key Words: Leucine-Glutamate-BrainBranched-chain aminotransferase-1 5N NMR-In vivo. J. Neurochem. 70, 1304Neurochem. 70, -1315Neurochem. 70, (1998.The branched-chain amino acids (BCAA) -leucine, isoleucine, and valine-are essential amino acids that readily cross the blood-brain barrier. Leucine is the predominant BCAA in most dietary proteins (Berry et al., 1989) and has the highest influx rate into the brain (Smith et al., 1987). In the brain, leucine has two metabolic fates: (a) incorporation into proteins and (b) transamination to a-ketoglutarate to form glutamate, catalyzed by branched-chain aminotransferase (BCAT; EC 2.6.1.42):

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“…An alternate source of neuronal glutamate, in addi tion to glutamine, is the glutamate formed from the transamination of a-ketoglutarate. Transam ination re actions are thought to be quite active in the brain [21], and treatment of brain tissue with aminooxyacetic acid, which inhibits transamination, lowers the release of glu tamate from cerebellar granule cells, a glutamatergic preparation [22][23][24].…”

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confidence: 99%

Brain Glutamate Metabolism: Neuronal-Astroglial Relationships

Yudkoff¹,

Nissim²,

Daikhin³

et al. 1993

Dev Neurosci

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The concentration of glutamate in the brain extracellular fluid must be kept low (∼3 µM)in order to maximize the signal-to-noise ratio upon the release of glutamate from neurons. In addition, the nerve endings require a supply of glutamate precursors that will not cause depolarization. The major precursor to neuronal glutamate is glutamine, which is synthesized in astrocytes and converted to glutamate in neurons. However, glutamine is not the sole source. Alanine also might serve as a precursor to glutamate via transamination, although this reaction is relatively inactive in synaptosomes. Finally, the branched-chain amino acids, and in particular leucine, appear to be very important precursors to glutamate and glutamine in astrocytes. By providing α-NH₂ groups for the synthesis of glutamine, leucine also abets the uptake into brain of neutral amino acids, which are transported in exchange for brain glutamine. In addition, the branched-chain ketoacids are readily reaminated to the cognate amino acids, in the process consuming glutamate. Intraneuronal consumption of glutamate via ketoacid reamination might serve to buffer internal [glutamate] and to modulate the releasable pool.

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Regional and Subcellular Distribution of Aminotransferases in Rat Brain

Cited by 56 publications

References 27 publications

Glutamate Metabolism in the Brain Focusing on Astrocytes

Glutamate Metabolism in the Brain Focusing on Astrocytes

Rate of Glutamate Synthesis from Leucine in Rat Brain Measured In Vivo by ¹⁵N NMR

Brain Glutamate Metabolism: Neuronal-Astroglial Relationships

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Regional and Subcellular Distribution of Aminotransferases in Rat Brain

Cited by 56 publications

References 27 publications

Glutamate Metabolism in the Brain Focusing on Astrocytes

Glutamate Metabolism in the Brain Focusing on Astrocytes

Rate of Glutamate Synthesis from Leucine in Rat Brain Measured In Vivo by 15N NMR

Brain Glutamate Metabolism: Neuronal-Astroglial Relationships

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Rate of Glutamate Synthesis from Leucine in Rat Brain Measured In Vivo by ¹⁵N NMR