Re-evaluation of amino-oxyacetate as an inhibitor

Smith, Stephen B.; Briggs, Stephanie; Triebwasser, K.C.; Freedland, R. A.

doi:10.1042/bj1620453

Cited by 52 publications

(19 citation statements)

References 10 publications

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“…Consistent with this, we found that the addition of aminooxyacetate, a general inhibitor of aminotransferases, essentially abolished urea synthesis (Fig. 1, 2nd row), also confirming results from other laboratories [22].…”

Section: Resultssupporting

confidence: 90%

Effects of inhibition of ornithine aminotransferase or of general aminotransferases on urea and citrulline synthesis and on the levels of acetylglutamate in isolated rat hepatocytes

Aniento¹,

Garcı́a-España²,

Portolés³

et al. 1988

Mol Cell Biochem

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Canaline and gabaculine, inhibitors of gamma-aminotransferases and thus of ornithine aminotransferase (E.C. 2.6.1.13), decreased the flow through ornithine carbamoyl transferase (E.C. 2.1.3.3) in isolated rat hepatocytes incubated with 10 mM NH4Cl and ornithine. The levels of acetylglutamate, an essential activator of carbamoyl phosphate synthetase (ammonia) (E.C. 6.3.4.16), were also decreased, suggesting that the inhibitors had also caused a decrease in the rate of carbamoyl phosphate synthesis. Under these conditions, ornithine appears to be a precursor of acetylglutamate, via ornithine aminotransferase, possibly as a consequence of glutamate synthesis. The influence of aminooxyacetate, an aminotransferase inhibitor, has also been examined.

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Section: Resultssupporting

confidence: 90%

Effects of inhibition of ornithine aminotransferase or of general aminotransferases on urea and citrulline synthesis and on the levels of acetylglutamate in isolated rat hepatocytes

Aniento¹,

Garcı́a-España²,

Portolés³

et al. 1988

Mol Cell Biochem

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“…Moreover, lactate release rates increased more than 10-fold in the presence of AOA. In contrast, AOA with pyruvate as a substrate significantly influenced neither the hemodynamic parameters nor the metabolite concentrations indicating that pyruvate can be metabolized after its uptake mitochondria (49 (65). These oscillations were sensitive to pharmacological manipulations of ryanodine-sensitive stores of intracellular Ca 2þ but not to TTX and L-type channel inhibitors (65).…”

Section: The Essential In Vivo Role Of the Masmentioning

confidence: 88%

The control of brain mitochondrial energization by cytosolic calcium: The mitochondrial gas pedal

et al. 2013

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This review focuses on problems of the intracellular regulation of mitochondrial function in the brain via the (i) supply of mitochondria with ADP by means of ADP shuttles and channels and (ii) the Ca 21 control of mitochondrial substrate supply. The permeability of the mitochondrial outer membrane for adenine nucleotides is low. Therefore rate dependent concentration gradients exist between the mitochondrial intermembrane space and the cytosol. The existence of dynamic ADP gradients is an important precondition for the functioning of ADP shuttles, for example CrP-shuttle. Cr at mM concentrations instead of ADP diffuses from the cytosol through the porin pores into the intermembrane space.

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“…In addition, we determined the influence of pyruvate on the oxidation of glutamate and glutamine since amino group acceptors can modulate glutamate metabolism [31] and may be therapeutically useful in pathological conditions characterized by ele vated concentrations of glutamate. In the present study we used the transaminase inhibitor aminooxyacetic acid (AOAA) [32] to obtain information about the impor tance of transamination enzymes in the metabolism of glutamate and glutamine by astrocytes.…”

Section: Introductionmentioning

confidence: 99%

New Insights into the Compartmentation of Glutamate and Glutamine in Cultured Rat Brain Astrocytes

Mc¹,

Jt²,

Jh³

et al. 1996

Dev Neurosci

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Studies from several groups have provided evidence that glutamate and glutamine are metabolized in different compartments in astrocytes. In the present study we measured the rates of ¹⁴C0₂ production from U-[¹⁴C]glutamate and U-[¹⁴C]glutamine, and utilized both substrate competition experiments and the transaminase inhibitor aminooxyacetic acid (AOAA) to obtain more information about the compartmentation of these substrates in cultured rat brain astrocytes. The rates of oxidation of 1 mM glutamine and glutamate were 26.4±1.4 and 63.0 ±7.4 nmol/h/mg protein, respectively. The addition of 1 mM glutamate decreased the rate of oxidation of glutamine to 26.3 % of the control rate, demonstrating that glutamate can effectively compete with the oxidation of glutamine by astrocytes. In contrast, the addition of 1 mM glutamine had little or no effect on the rate of oxidation of glutamate by astrocytes, demonstrating that the glutamate produced intracellularly from exogenous glutamine does not dilute the glutamate taken up from the media. The addition of 5 mM AOAA decreased the rate of ¹⁴C0₂ production from glutamine to 29.2% of the control rate, consistent with earlier studies by our group. The addition of 5 mM AOAA decreased the rate of oxidation of concentrations of glutamate ≤0.1 mM by ∼50%, but decreased the oxidation of 0.5–1 mM glutamate by only ∼20%, demonstrating that a substantial portion of glutamate enters the tricarboxylic acid (TCA) cycle via glutamate dehydrogenase (GDH) rather than transamination, and that as the concentration of glutamate increases the relative proportion entering the TCA cycle via GDH also increases. To determine if the presence of an amino group acceptor (i.e. a ketoacid) would increase the rate of metabolism of glutamate, pyruvate was added in some experiments. Addition of 1 mM pyruvate increased the rate of oxidation of glutamate, and the increase was inhibited by AOAA, consistent with enhanced entry of glutamate into the TCA cycle via transamination in the presence of pyruvate. Enzymatic studies showed that pyruvate increased the activity of mitochondrial aspartate aminotransferase (AAT). Overall, the data demonstrate that glutamate formed intracellularly from glutamine enters the TCA cycle primarily via transamination, but does not enter the same TCA cycle compartment as glutamate taken up from the extracellular milieu. In contrast, extracellular glutamate enters the TCA cycle in astrocytes via both transamination and GDH, and can compete with, or dilute, the oxidation of glutamate produced intracellularly from glutamine.

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Re-evaluation of amino-oxyacetate as an inhibitor

Cited by 52 publications

References 10 publications

Effects of inhibition of ornithine aminotransferase or of general aminotransferases on urea and citrulline synthesis and on the levels of acetylglutamate in isolated rat hepatocytes

Effects of inhibition of ornithine aminotransferase or of general aminotransferases on urea and citrulline synthesis and on the levels of acetylglutamate in isolated rat hepatocytes

The control of brain mitochondrial energization by cytosolic calcium: The mitochondrial gas pedal

New Insights into the Compartmentation of Glutamate and Glutamine in Cultured Rat Brain Astrocytes

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