Effect of pH and a-Ketoglutarate on Mitochondrial Ammonia Production1

Schoolwerth, Anton C.; Strzelecki, T; LaNoue, K. F.; Hoover, W. J.

doi:10.1159/000406628

Cited by 14 publications

(7 citation statements)

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“…Schoolwerth and LaNoue [65] suggested in 1980 that the link between the two pathways might be 2-oxoglutarate. Recent studies by LaNoue and coworkers [66,671 and the data presented in this paper indicate that this is, indeed, the case (see Table 7). …”

Section: Discussionsupporting

confidence: 79%

Bicarbonate and the Pathway of Glutamate Oxidation in Isolated Rat‐Liver Mitochondria

Wanders¹,

Meijer²,

Groen³

et al. 1983

European Journal of Biochemistry

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1. The factors affecting the pathway of glutamate oxidation were studied in isolated rat-liver mitochondria in incubations of 2-3 min.2. It was found that bicarbonate at a physiological concentration has a profound effect on the pathway of glutamate oxidation. Ammonia formation via glutamate dehydrogenase is stimulated by bicarbonate [from 5.48 0.73 (n = 8) nmol . min-' . mg protein-'], whereas aspartate formation via the transamination pathway is inhibited [from 38.41 5 2.24 (n = 9) to 24.56 3.28 (n = 6) nmol . min-l . mg protein-' 3.0.29 (n = 10) to 9.57 3. Bicarbonate has no effect on the rate of transport of glutamate via the glutamate-hydroxyl translocator. 4. The interaction of bicarbonate with the pathway of glutamate oxidation occurs primarily at the level of succinate dehydrogenase, due to competitive inhibition of the enzyme by bicarbonate.5. Inhibition by bicarbonate of the transamination pathway leads to a decrease in intramitochondrial 2-oxoglutarate, so that the deamination pathway is stimulated.6. Using an equation which describes flux through glutamate dehydrogenase kinetically, it could be shown that the bicarbonate-induced decrease in intramitochondrial2-oxoglutarate quantitatively accounts for the enhanced rate of deamination.7. It is concluded that in the intact liver flux through glutamate dehydrogenase is sufficient to account for the ammonia formation required for urea synthesis from substrates such as alanine.

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Section: Discussionsupporting

confidence: 79%

Bicarbonate and the Pathway of Glutamate Oxidation in Isolated Rat‐Liver Mitochondria

Wanders¹,

Meijer²,

Groen³

et al. 1983

European Journal of Biochemistry

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“…Since then, its main properties have been studied in intact mitochondria (15)(16)(17)(18)(19)(20)(21)(22)(23)(24). However, the protein responsible for the glutamate carrier had not been identified hitherto.…”

Section: Discussionmentioning

confidence: 99%

“…However, when ammonia rather than glutamate is the major nitrogen source for urea synthesis or when glutamine is generated intramitochondrially, for example by proline oxidation, the GC may operate in the reverse direction to limit the intramitochondrial accumulation of glutamate (21,33). Furthermore, prevention of glutamate efflux from mitochondria by cytosolic H ϩ in kidney tubular cells may play an important role in the kidney response to metabolic acidosis by contributing to increased flux through glutamate dehydrogenase and hence to increased ammonia production (and excretion) from glutamine (16,22).…”

Section: Discussionmentioning

confidence: 99%

“…The GC has a high K m value and a low activity and was suggested to limit the effective activity of glutamate dehydrogenase, which is located exclusively in mitochondria, in the direction of glutamate deamination (19,20,23). The activity of glutamate transport was found to be higher in liver than in kidney (22) and heart (24), as anticipated from the central role of glutamate dehydrogenase in liver nitrogen metabolism.…”

Section: And References Therein)mentioning

confidence: 99%

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Identification of the Mitochondrial Glutamate Transporter

Fiermonte¹,

Palmieri²,

Todisco³

et al. 2002

Journal of Biological Chemistry

180

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“…However further investigation seems necessary both to ascertain the occurrence of such translocators in mitochondria from different sources and to identify the existence of special carriers involved in specific metabolism. In particular, in kidney in addition to glutamate/aspartate [2], dicarboxylate [3], glutamine [4, 51, oxoglutarate [6], fumarate [7] and glutamate/ OH- [8], we have shown the existence of malate/oxaloacetate and pyruvate/oxaloacetate translocators [9]. Recently the existence in kidney mitochondria of an ornithine/Pi translocator has been shown by fluorimetric and photometric measurements [lo].…”

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confidence: 98%

Ornithine/phosphate antiport in rat kidney mitochondria

Passarella¹,

Atlante²,

Quagliariello³

1990

European Journal of Biochemistry

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['4C]Ornithine uptake by rat kidney mitochondria has been investigated according to the stop inhibitor method by using praseodimium chloride as an inhibitor. The existence of an ornithine/Pi exchange was found occurring with 1 : 1 stoichiometry. Both uptake and efflux follow first-order kinetics with a k of 2.4 min-'. Uptake increases with increasing pH. The activation energy for the process is 58.6 kJ/mol and Qlo is 2.6. Ornithine/P, exchange is electrical and energy-dependent, as suggested by the sensitivity of the process to the ionophores valinomycin and nigericin. Measurements both of proton movement across the mitochondrial membrane and of membrane potential strongly suggest that ornithine uptake into mitochondria is driven by the electrochemical proton gradient via the dependent ornithine/Pi translocator and ApH-dependent Pi carrier.Mitochondria can only function if there is a continual interchange of metabolites and end products with the cell cytosol; thus about 12 different transporters have been identified in mammalian mitochondria [l] to allow for movement of substrates from cytosol to mitochondria and vice versa. However further investigation seems necessary both to ascertain the occurrence of such translocators in mitochondria from different sources and to identify the existence of special carriers involved in specific metabolism. In particular, in kidney in addition to glutamate/aspartate [2], dicarboxylate [3], glutamine [4, 51, oxoglutarate [6], fumarate [7] and glutamate/ OH- [8], we have shown the existence of malate/oxaloacetate and pyruvate/oxaloacetate translocators [9]. Recently the existence in kidney mitochondria of an ornithine/Pi translocator has been shown by fluorimetric and photometric measurements [lo]. To gain further insight into ornithine uptake by rat kidney mitochondria, an isotopic study appears worthwhile. Thus this paper deals with experiments in which [14C]ornithine uptake by rat kidney mitochondria has been measured according to the stop inhibitor method and certain aspects of the process investigated in detail. Ornithine/Pi exchange has been proved to occur electrically with a 1 : 1 stoichiometry. MATERIALS AND METHODS MaterialsAminooxyacetic, L-glutamic, L-malic and methylglutamic and other amino acids, L-ornithine, mersalyl, EGTA, Triton X-100, rotenone, nigericin, valinomycin, carbonylcyanide ptrifluoromethoxyphenylhydrazone (FCCP), safranine 0 and metal chlorides were obtained from Sigma (St Louis, USA);

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Effect of pH and a-Ketoglutarate on Mitochondrial Ammonia Production1

Cited by 14 publications

References 0 publications

Bicarbonate and the Pathway of Glutamate Oxidation in Isolated Rat‐Liver Mitochondria

Bicarbonate and the Pathway of Glutamate Oxidation in Isolated Rat‐Liver Mitochondria

Identification of the Mitochondrial Glutamate Transporter

Ornithine/phosphate antiport in rat kidney mitochondria

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