Aminotransferase Activity in Brain

Benuck, M.; Lajtha, Ábel

doi:10.1016/s0074-7742(08)60208-1

Cited by 28 publications

(25 citation statements)

References 224 publications

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“…These findings highlight an adaptive regulatory gene induction of the ammonium-metabolizing transaminases Gpt2 and Oat . While GPT2 reversibly catalyzes the transfer of an amino group from alanine to 2-oxoglutarate to form glutamate and pyruvate, OAT generates glutamate and Δ1-pyrroline-5-carboxylate by transfer of the delta-amino group of ornithine to 2-oxoglutarate [ 30 , 31 ].…”

Section: Resultsmentioning

confidence: 99%

Pharmacologic rescue of hyperammonemia-induced toxicity in zebrafish by inhibition of ornithine aminotransferase

et al. 2018

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Hyperammonemia is the common biochemical hallmark of urea cycle disorders, activating neurotoxic pathways. If untreated, affected individuals have a high risk of irreversible brain damage and mortality. Here we show that acute hyperammonemia strongly enhances transamination-dependent formation of osmolytic glutamine and excitatory glutamate, thereby inducing neurotoxicity and death in ammoniotelic zebrafish larvae via synergistically acting overactivation of NMDA receptors and bioenergetic impairment induced by depletion of 2-oxoglutarate. Intriguingly, specific and irreversible inhibition of ornithine aminotransferase (OAT) by 5-fluoromethylornithine rescues zebrafish from lethal concentrations of ammonium acetate and corrects hyperammonemia-induced biochemical alterations. Thus, OAT inhibition is a promising and effective therapeutic approach for preventing neurotoxicity and mortality in acute hyperammonemia.

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Section: Resultsmentioning

confidence: 99%

Pharmacologic rescue of hyperammonemia-induced toxicity in zebrafish by inhibition of ornithine aminotransferase

et al. 2018

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“…The enzyme catalyzes the formation of glutamate for the synthesis of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). The activity of AAT is comparable to the enzymes of the glycolytic and respiratory cycles [93]. …”

Section: Aspartate Aminotransferase (Aat)mentioning

confidence: 99%

Studying enzymes by in vivo 13C magnetic resonance spectroscopy

Shen²

2009

Progress in Nuclear Magnetic Resonance Spectroscopy

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“…Both enzymes are involved in glutamate metabolism. AST catalyses the conversion of aspartate and 2-oxoglutarate to oxaloacetate and glutamate, or the reverse reaction with pyridoxal 5-phosphate (PLP) as a coenzyme (15,16). It also takes part in the synthesis of the neurotransmitter like glutamate in glutamatergic cells (17,18) and catalyzes the production of glutamate for GABA synthesis (16).…”

Section: Introductionmentioning

confidence: 99%

Influence of Proline on Rat Brain Activities of Alanine Aminotransferase, Aspartate Aminotransferase and Acid Phosphatase

2004

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Hyperprolinemia type II (HPII) is an autosomal recessive disorder caused by the severe deficiency of enzyme delta1-pyrroline-5-carboxylic acid dehydrogenase leading to tissue accumulation of proline. Chronic administration of Pro led to significant reduction of cytosolic ALT activity of olfactory lobes (50.57%), cerebrum (40%) and medulla oblongata (13.71%) only. Whereas mitochondrial ALT activity was reduced significantly in, all brain regions such as olfactory lobes (73.23%), cerebrum (70.26%), cerebellum (65.39%) and medulla oblongata (65.18%). The effect of chronic Pro administration on cytosolic AST activity was also determined. The cytosolic AST activity from olfactory lobes, cerebrum and medulla oblongata reduced by 75.71, 67.53 and 76.13%, respectively while cytosolic AST activity from cerebellum increased by 28.05%. The mitochondrial AST activity lowered in olfactory lobes (by 72.45%), cerebrum (by 78%), cerebellum (by 49.56%) and medulla oblongata (by 69.30%). In vitro studies also showed increase in brain tissue proline and decrease in glutamate levels. In vitro studies indicated that proline has direct inhibitory effect on these enzymes and glutamate levels in brain tissue showed positive correlation with AST and ALT activities. Acid phosphatase (ACP) activity reduced significantly in olfactory lobes (40.33%) and cerebrum (20.82%) whereas it elevated in cerebellum (97.32%) and medulla oblongata (76.33%). The histological studies showed degenerative changes in brain. Following proline treatment, the animals became sluggish and showed low responses to tail pricks and lifting by tails and showed impaired balancing. These observations indicate influence of proline on AST, ALT and ACP activities of different brain regions leading to lesser synthesis of glutamate thereby causing neurological dysfunctions.

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Aminotransferase Activity in Brain

Cited by 28 publications

References 224 publications

Pharmacologic rescue of hyperammonemia-induced toxicity in zebrafish by inhibition of ornithine aminotransferase

Pharmacologic rescue of hyperammonemia-induced toxicity in zebrafish by inhibition of ornithine aminotransferase

Studying enzymes by in vivo 13C magnetic resonance spectroscopy

Influence of Proline on Rat Brain Activities of Alanine Aminotransferase, Aspartate Aminotransferase and Acid Phosphatase

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