Cellular mechanisms of the antiammoniagenic effect of ketone bodies in the dog

Lemieux, Guy; Pichette, Carole; Vinay, Patrick; Gougoux, A.

doi:10.1152/ajprenal.1980.239.5.f420

Cited by 16 publications

(13 citation statements)

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“…Metabolism of ketone bodies also sequesters free cardiac coenzyme A as acetoacetyl-CoA, thereby diminishing flux through ·-ketoglutarate dehydrogenase, for which coenzyme A is a reactant [34]. In dog kidney the infusion of either acetoacetate or 3-OH-butyrate markedly increased glutamate production and decreased aspartate output [35].…”

Section: Discussionmentioning

confidence: 99%

Ketone Bodies and Brain Glutamate and GABA Metabolism

Daikhin

Yudkoff

1998

Dev Neurosci

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The effects of ketone bodies on brain metabolism of glutamate and GABA were studied in three different systems: synaptosomes, cultured astrocytes and the whole animal. In synaptosomes the addition of either acetoacetate or 3-OH-butyrate was associated with diminished consumption of glutamate via transamination to aspartate and increased formation of labelled GABA from either L-[²H₅-2,3,3,4,4]glutamine or L-[¹⁵N]glutamine. There was no effect of ketone bodies on synaptosomal GABA transamination. An increase of total forebrain GABA and a diminution of aspartate was noted when mice were injected intraperitoneally with 3-OH-butyrate. In cultured astrocytes the addition of acetoacetate to the medium was associated with a significantly enhanced rate of citrate production and with a diminution in the rate of conversion of [¹⁵N]glutamate to [¹⁵N]aspartate. These data are consistent with the hypothesis that the metabolism of ketone bodies to acetyl-CoA results in a diminution of the pool of brain oxaloacetate, which is consumed in the citrate synthetase reaction (oxaloacetate + acetyl-CoA → citrate). As less oxaloacetate is available to the aspartate aminotransferase reaction, thereby lowering the rate of glutamate transamination, more glutamate becomes accessible to the glutamate decarboxylase pathway, thereby favoring the synthesis of GABA.

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Section: Discussionmentioning

confidence: 99%

Ketone Bodies and Brain Glutamate and GABA Metabolism

Daikhin

Yudkoff

1998

Dev Neurosci

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“…many hypotheses concerning enhancement of ammoniagenesis during acidosis in dogs consider its concentration as a potential regulator of GDH [4][5][6],…”

Section: Discussionmentioning

confidence: 99%

“…The importance of other pathways for ammoniagenesis in dogs is uncertain [2][3][4], 2-Oxoglutarate occupies an important position in the production of ammonia. Since the GDH is potentially reversible, an accumulation of 2-oxoglutarate by canine kidneys could regulate glutamate ammonia genesis by end-product inhibition [5,6]. In turn, a buildup ofglutamate might then slow the deamidation of glutamine via inhibition of PDG [7,8], Accordingly, a decrease in the Rx renal concentration of 2-oxoglutarate could reverse the chain of events, and augment arnmoniagenesis through GDH and PDG [9], Another possibility exists whereby 2-oxoglutarate buildup controls renal am monia production.…”

mentioning

confidence: 99%

“…Thus, lesser concentrations of 2-oxoglutarate could enhance ammoniagenesis via deinhibition of mitochondrial trans port of glutamine. By either mechanism, the concentration of 2-oxoglutarate is poten tially an important regulator of ammonia production, as pointed out in recent reviews on the subject [4,11], The renal concentra tion of 2-oxoglutarate has been considered as a potential regulator of renal ammoniagenesis in dogs [4][5][6], Infusions of2-oxoglutarate into dogs have been shown to decrease renal arnmoniagenesis [12.13]: however, the mechanism for the depression was not ascer tained.…”

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confidence: 99%

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Effects of 2-Oxoglutarate Concentrations on Canine Slice Ammoniagenesis

Risquez¹,

Gaydos²,

Preuss³

1983

Kidney Blood Press Res

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The concentration of renal 2-oxoglutarate has been proposed as an important regulator of ammoniagenesis in dog kidneys. In the present study, canine kidney slices produced less ammonia from glutamine and glutamate when 2-oxoglutarate was present in the incubation medium. However, the addition of arsenite, a metabolic blocker known to block 2-oxoglutarate metabolism and lead to its accumulation, overcame 2-oxoglutarate inhibition of ammoniagenesis when glutamine and glutamate were the ammonia precursors. Therefore, metabolism of 2-oxoglutarate, rather than its concentration, governed ammonia production from glutamine and glutamate in incubating dog renal tissue. In contrast to the results with 2-oxoglutarate, inhibition of glutamine ammoniagenesis by glutamate was not overcome by arsenite. The results suggest that renal ammonia adaptation in acidotic dogs cannot be ascribed to a theory based upon 2-oxoglutarate concentrations controlling the direction of the glutamate dehydrogenase pathway (GDH), decreasing glutamine transport, or directly inhibiting GDH enzyme activity.

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“…For example, ketone bodies directly inhibit hepatic glucose production, adipocyte lipolysis (Henry et al, 1990), glucose utilization by extrahepatic tissues (Robinson and Williamson, 1980), and glutamine metabolism in the small intestine (Hanson and Parsons, 1978) and kidneys (Lemieux et al, 1980) in mammals. Moreover, in chicken, it has been reported that ketone bodies modulate protein turnover (Wu and Thompson, 1990) and amino acid metabolism (Wu and Thompson, 1988) in the skeletal muscles.…”

Section: Introductionmentioning

confidence: 99%

Plasma Lipid Profiles and Redox Status are Modulated in a Ketogenic Diet-Induced Chicken Model of Ketosis

et al. 2013

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Ketone bodies such as β-hydroxybutyrate and acetoacetate have physiological functions in addition to being used as an energy source. In order to assess the effect of elevated ketogenesis on blood lipid profiles and redox status, a ketogenic diet (KD), a high-fat, low-carbohydrate, and low-protein diet, was fed to chicken for 4 weeks. Plasma β-hydroxybutyrate, but not acetoacetate, concentrations were significantly increased by KD feeding for 2 and 4 weeks. The KD also induced elevation of plasma non-esterified fatty acid (NEFA) and total cholesterol concentrations, whereas plasma triglyceride concentration was decreased. Plasma total antioxidant activity in chicken with ketosis induced by KD was lower than that of the control. However, the level of plasma TBARs, an oxidative stress marker, was also reduced by KD feeding. A reduction of energy intake was observed in chickens fed the KD; therefore, the effect of a restricted diet (RD) was also investigated. Plasma β-hydroxybutyrate concentration, lipid (total cholesterol and NEFA) concentration, and redox status were not affected by RD feeding. These data suggest that a high-fat, lowcarbohydrate, and low-protein diet induces ketosis by elevating blood β-hydroxybutyrate concentration in chicken. Under conditions of ketosis induced by the KD, total antioxidant capacity was reduced along with a modulation of the blood lipid profile in chicken.

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Cellular mechanisms of the antiammoniagenic effect of ketone bodies in the dog

Cited by 16 publications

References 0 publications

Ketone Bodies and Brain Glutamate and GABA Metabolism

Ketone Bodies and Brain Glutamate and GABA Metabolism

Effects of 2-Oxoglutarate Concentrations on Canine Slice Ammoniagenesis

Plasma Lipid Profiles and Redox Status are Modulated in a Ketogenic Diet-Induced Chicken Model of Ketosis

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