Les Voies Principales De L'assimilation Et Dissimilation De L'Azote Chez Les Animaux

Braunstein, A. E.

doi:10.1002/9780470122648.ch5

Cited by 4 publications

(3 citation statements)

References 76 publications

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“…In 1957, Braunstein (the discoverer of aminotransferases (transaminases)) pointed out that coupling of an aminotransferase reaction: Equation (4) to the GDH reaction: Equation (5), shown as the reverse direction of Equation (2), provides a means of generating ammonia or of incorporating ammonia into several of the commonly-occurring amino acids: Equation (6). Braunstein coined the words “transdeamination” and “transreamination” for the forward and reverse directions of Equation (6) [ 18 ]. (For a review see [ 19 ]).…”

Section: Glutamate Formation In the Brain—important Roles Of Glutamentioning

confidence: 99%

Central Role of Glutamate Metabolism in the Maintenance of Nitrogen Homeostasis in Normal and Hyperammonemic Brain

2016

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Glutamate is present in the brain at an average concentration—typically 10–12 mM—far in excess of those of other amino acids. In glutamate-containing vesicles in the brain, the concentration of glutamate may even exceed 100 mM. Yet because glutamate is a major excitatory neurotransmitter, the concentration of this amino acid in the cerebral extracellular fluid must be kept low—typically µM. The remarkable gradient of glutamate in the different cerebral compartments: vesicles > cytosol/mitochondria > extracellular fluid attests to the extraordinary effectiveness of glutamate transporters and the strict control of enzymes of glutamate catabolism and synthesis in well-defined cellular and subcellular compartments in the brain. A major route for glutamate and ammonia removal is via the glutamine synthetase (glutamate ammonia ligase) reaction. Glutamate is also removed by conversion to the inhibitory neurotransmitter γ-aminobutyrate (GABA) via the action of glutamate decarboxylase. On the other hand, cerebral glutamate levels are maintained by the action of glutaminase and by various α-ketoglutarate-linked aminotransferases (especially aspartate aminotransferase and the mitochondrial and cytosolic forms of the branched-chain aminotransferases). Although the glutamate dehydrogenase reaction is freely reversible, owing to rapid removal of ammonia as glutamine amide, the direction of the glutamate dehydrogenase reaction in the brain in vivo is mainly toward glutamate catabolism rather than toward the net synthesis of glutamate, even under hyperammonemia conditions. During hyperammonemia, there is a large increase in cerebral glutamine content, but only small changes in the levels of glutamate and α-ketoglutarate. Thus, the channeling of glutamate toward glutamine during hyperammonemia results in the net synthesis of 5-carbon units. This increase in 5-carbon units is accomplished in part by the ammonia-induced stimulation of the anaplerotic enzyme pyruvate carboxylase. Here, we suggest that glutamate may constitute a buffer or bulwark against changes in cerebral amine and ammonia nitrogen. Although the glutamate transporters are briefly discussed, the major emphasis of the present review is on the enzymology contributing to the maintenance of glutamate levels under normal and hyperammonemic conditions. Emphasis will also be placed on the central role of glutamate in the glutamine-glutamate and glutamine-GABA neurotransmitter cycles between neurons and astrocytes. Finally, we provide a brief and selective discussion of neuropathology associated with altered cerebral glutamate levels.

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Section: Glutamate Formation In the Brain—important Roles Of Glutamentioning

confidence: 99%

Central Role of Glutamate Metabolism in the Maintenance of Nitrogen Homeostasis in Normal and Hyperammonemic Brain

2016

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“…The accumulating amino acids are probably non-essential and their carbon skeletons can be synthesized from glucose, acetate, and other amino acids (Bishop, 1976). Several fixation sites for amino nitrogen during hyperosmotic adjustment have been suggested (the purine nucleotide cycle: Braunstein, 1957; Bishop and Barnes, 1971;Lowenstein, 1972; serine dehydrase: Gilles, 1969; direct fixation of ammonia via the glutamate dehydrogenase: Reiss et al, 1977;Chaplin et al, 1970).…”

Section: Hyperosmotic Adjustmentmentioning

confidence: 99%

“…Because glutamate levels do not increase when molluscs are subjected to hyperosmotic stress, increased fixation at glutamate dehydrogenase is unlikely for molluscs (Bishop et al, 1981). However, treatment of ribbed mussel tissues with Lcycloserine or aminooxyacetic acid (two inhibitors of glutamate-linked transaminases: Braunstein, 1957) changes the pattern of free amino acid accumulation. Specifically, aminooxyacetic acid treatment significantly decreases proline and alanine levels while not affecting 6-alanine or taurine levels.…”

Section: Hyperosmotic Adjustmentmentioning

confidence: 99%

Purification and properties of the malic enzyme and the malate dehydrogenases from the gill tissue of the ribbed mussel (Modiolus demissus)

Brodey

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The Role of Glutamine Synthetase and Glutamate Dehydrogenase in Cerebral Ammonia Homeostasis

Cooper

2012

Neurochem Res

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In the brain, glutamine synthetase (GS), which is located predominantly in astrocytes, is largely responsible for the removal of both blood-derived and metabolically generated ammonia. Thus, studies with [13N]ammonia have shown that about 25% of blood-derived ammonia is removed in a single pass through the rat brain and that this ammonia is incorporated primarily into glutamine (amide) in astrocytes. Major pathways for cerebral ammonia generation include the glutaminase reaction and the glutamate dehydrogenase (GDH) reaction. The equilibrium position of the GDH-catalyzed reaction in vitro favors reductive amination of α-ketoglutarate at pH 7.4. Nevertheless, only a small amount of label derived from [13N]ammonia in rat brain is incorporated into glutamate and the α-amine of glutamine in vivo. Most likely the cerebral GDH reaction is drawn normally in the direction of glutamate oxidation (ammonia production) by rapid removal of ammonia as glutamine. Linkage of glutamate/α-ketoglutarate-utilizing aminotransferases with the GDH reaction channels excess amino acid nitrogen toward ammonia for glutamine synthesis. At high ammonia levels and/or when GS is inhibited the GDH reaction coupled with glutamate/α-ketoglutarate-linked aminotransferases may, however, promote the flow of ammonia nitrogen toward synthesis of amino acids. Preliminary evidence suggests an important role for the purine nucleotide cycle (PNC) as an additional source of ammonia in neurons (Net reaction: L-Aspartate + GTP + H2O → Fumarate + GDP + Pi + NH3) and in the beat cycle of ependyma cilia. The link of the PNC to aminotransferases and GDH/GS and its role in cerebral nitrogen metabolism under both normal and pathological (e.g. hyperammonemic encephalopathy) conditions should be a productive area for future research.

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Les Voies Principales De L'assimilation Et Dissimilation De L'Azote Chez Les Animaux

Cited by 4 publications

References 76 publications

Central Role of Glutamate Metabolism in the Maintenance of Nitrogen Homeostasis in Normal and Hyperammonemic Brain

Central Role of Glutamate Metabolism in the Maintenance of Nitrogen Homeostasis in Normal and Hyperammonemic Brain

Purification and properties of the malic enzyme and the malate dehydrogenases from the gill tissue of the ribbed mussel (Modiolus demissus)

The Role of Glutamine Synthetase and Glutamate Dehydrogenase in Cerebral Ammonia Homeostasis

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