On glutaminase activity in mammalian synaptosomes

Bradford, H. F.; Ward, H. K.

doi:10.1016/0006-8993(76)90212-2

Cited by 202 publications

(61 citation statements)

References 18 publications

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“…To replenish the neurotransmitter pool of glutamate, an intensive glutamine flow from astrocytes to glutamatergic neurons must occur. Once glutamine is taken up into the glutamatergic neuron, phosphate-activated glutaminase converts it into glutamate (11)(12)(13). Glutamate is then sequestered in synaptic vesicles to be made available for regulated neurosecretion (14,15).…”

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confidence: 99%

Cloning and Functional Identification of a Neuronal Glutamine Transporter

Varoqui¹,

Zhu²,

Yao³

et al. 2000

Journal of Biological Chemistry

271

214

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Glutamine is the preferred precursor for the neurotransmitter pool of glutamate, the major excitatory transmitter in the mammalian central nervous system. We have isolated a complementary DNA clone (designated GlnT) encoding a plasma membrane glutamine transporter from glutamatergic neurons in culture, and its properties have been examined using the T7 vaccinia system in fibroblasts. When GlnT is transfected into CV-1 cells, L-glutamine is the preferred substrate. Transport is Na ؉ -dependent and inhibited by ␣-methylaminoisobutyric acid, a specific inhibitor of neutral amino acid transport system A. Kinetic analysis of glutamine uptake by GlnT is saturable, with a Michaelis constant (K m ) of 489 ؎ 88 M at pH 7.4. Glutamine uptake mediated by GlnT is pH-sensitive with a 5-fold greater efficiency of uptake at pH 8.2 than at pH 6.6. Only the maximal velocity of transport increases without a significant change in K m . The distribution of GlnT mRNA and protein in the central nervous system is widespread and is expressed on neurons that use glutamate as their neurotransmitter. In cultured cerebellar granule cells, GlnT is expressed only on neurons and is absent from astrocytes. GlnT expression increases concomitantly with the morphologic and functional differentiation of these cells in vitro, consistent with its role of supplying glutamatergic neurons with their neurotransmitter precursor. GlnT is the first member of the system A family of neutral amino acid transporters with 11 putative membrane-spanning domains and is a potential target to modulate presynaptic glutamatergic function.

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mentioning

confidence: 99%

Cloning and Functional Identification of a Neuronal Glutamine Transporter

Varoqui¹,

Zhu²,

Yao³

et al. 2000

Journal of Biological Chemistry

271

214

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“…Under normal physiological conditions the small intestine is the main glutamine-utilizing tissue; others are quantitatively far less important (see section 3). For example, glutamine is an oxidative fuel of synaptosomes and a precursor of both excitatory (glutamate and aspartate) and of inhibitory (y-aminobutyric acid) neurotransmitters [60], yet the metabolism of the brain, as measured by arteriovenous differences, appears to result in a net glutamine synthesis [54,61, 621. There are conditions (metabolic acidosis and lactation) during which the kidney and mammary gland, respectively, make extra demands on the glutamine supply. In normal acid-base balance there is no uptake of glutamine by rat kidney in vivo [7,63,64], essentially confirming earlier work of Pitts [65] who found that glutamine hydrolysis was almost exactly balanced by glutamine synthesis in the non-acidotic rat kidney.…”

Section: Other Reactions Involving Glutaminementioning

confidence: 99%

Glutamine metabolism in the rat

Lund

1980

FEBS Letters

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“…Glutamine uptake into neurons is mediated largely by a System A-like transporter (5) and is a crucial step in the "glutamate-glutamine cycle" (6 -8). The neuronal enzyme phosphateactivated glutaminase (PAG) catalyzes the hydrolysis of glutamine to glutamate (9), which can also serve as a direct GABA precursor (10). Specific vesicular transporters package glutamate or GABA for synaptic release.…”

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confidence: 99%

Functional Properties and Cellular Distribution of the System A Glutamine Transporter SNAT1 Support Specialized Roles in Central Neurons

Mackenzie

Schäfer

Erickson³

et al. 2003

Journal of Biological Chemistry

133

149

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Glutamine, the preferred precursor for neurotransmitter glutamate and GABA, is likely to be the principal substrate for the neuronal System A transporter SNAT1 in vivo. We explored the functional properties of SNAT1 (the product of the rat Slc38a1 gene) by measuring radiotracer uptake and currents associated with SNAT1 expression in Xenopus oocytes and determined the neuronal-phenotypic and cellular distribution of SNAT1 by confocal laser-scanning microscopy alongside other markers. We found that SNAT1 mediates transport of small, neutral, aliphatic amino acids including glutamine (K 0.5 Ϸ 0.3 mM), alanine, and the System A-specific analogue 2-(methylamino)isobutyrate. Amino acid transport is driven by the Na ؉ electrochemical gradient. The voltage-dependent binding of Na ؉ precedes that of the amino acid in a simultaneous transport mechanism. Li ؉ (but not H ؉ ) can substitute for Na ؉ but results in reduced V max . In the absence of amino acid, SNAT1 mediates Na ؉ -dependent presteady-state currents (Q max Ϸ 9 nC) and a nonsaturable cation leak with selectivity Na ؉ , Li ؉ > > H ؉ , K ؉ . Simultaneous flux and current measurements indicate coupling stoichiometry of 1 Na ؉ per 1 amino acid. SNAT1 protein was detected in somata and proximal dendrites but not nerve terminals of glutamatergic and GABAergic neurons throughout the adult CNS. We did not detect SNAT1 expression in astrocytes but detected its expression on the luminal membranes of the ependyma. The functional properties and cellular distribution of SNAT1 support a primary role for SNAT1 in glutamine transport serving the glutamate/GABA-glutamine cycle in central neurons. Localization of SNAT1 to certain dopaminergic neurons of the substantia nigra and cholinergic motoneurons suggests that SNAT1 may play additional specialized roles, providing metabolic fuel (via ␣-ketoglutarate) or precursors (cysteine, glycine) for glutathione synthesis.

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On glutaminase activity in mammalian synaptosomes

Cited by 202 publications

References 18 publications

Cloning and Functional Identification of a Neuronal Glutamine Transporter

Cloning and Functional Identification of a Neuronal Glutamine Transporter

Glutamine metabolism in the rat

Functional Properties and Cellular Distribution of the System A Glutamine Transporter SNAT1 Support Specialized Roles in Central Neurons

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