Effects of methylmalonate and propionate on uptake of glucose and ketone bodies in vitro by brain of developing rats

Dutra, Janice Coelho; Wajner, Moaçir; Wannmacher, C. M. D.; Dutra-Filho, Carlos Severo; Wannmacher, Clóvis Milton Duval

doi:10.1016/0885-4505(91)90008-9

Cited by 25 publications

(20 citation statements)

References 12 publications

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“…We therefore assume that brain lactate release in our assay represents lactate production. Total brain glucose uptake also increased with MMA concentrations in the incubation medium (F(3,28) = 2.215, p < 0.05) (Table 1) in a dose-dependent pattern (regression coefficient 0.774, p < 0.05), thus confirming our previous findings (Dutra et al, 1989(Dutra et al, , 1991. The table also shows that lactate production was proportional to glucose utilization, leading one to speculate that the increment in brain glucose uptake caused by MMA was mainly diverted to lactate.…”

Section: Methodssupporting

confidence: 89%

“…Very little has been done to identify the mechanisms underlying the neurological dysfunction of these patients. We have previously found that MMA induces a higher glucose utilization by brain of fasting young rats (Dutra et al, 1989(Dutra et al, , 1991. Since brain of young mammals releases considerable amounts of lactate into blood (Hawkins et aI., 1971;Cremer and Health, 1974;Dahlquist and Persson, 1976), in this study we investigated the effect of MMA on lactate and CO2 production by rat brain in an attempt to better understand the fate of the augmented brain glucose uptake provoked by this acidic metabolite.…”

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confidence: 95%

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Effect of methylmalonate onin vitro lactate release and carbon dioxide production by brain of suckling rats

Wajner

Dutra

Cardoso

et al. 1991

J of Inher Metab Disea

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Methylmalonate (MMA) accumulates in the tissues of patients with methylmalonic acidaemia, who present severe neurological signs soon after birth and later mental retardation. Attempting to understand the pathophysiology of the disorder, we investigated the effects of MMA on brain glucose uptake, lactate release and CO2 production. Glucose uptake and lactate release were studied by incubating 40 microns wide brain prisms from 15-day-old rats in Krebs-Ringer bicarbonate buffer, pH 7.0, containing 5.0 mmol/L glucose and one of three concentrations of MMA (1.0, 2.5 and 5.0 mmol/L). Controls did not contain MMA in the incubation medium. MMA induced a significant increase of lactate production in a dose-dependent pattern that was proportional to glucose uptake by the brain prisms. We also studied the influence of MMA on brain CO2 production from [2-14C]glucose and [U-14C]acetate by incubating brain prisms in the same buffer in the presence of the substrates with (experimental groups) or without (controls) 5.0 mmol/L MMA. MMA significantly reduced CO2 formation from both substrates.

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Section: Methodssupporting

confidence: 89%

mentioning

confidence: 95%

Effect of methylmalonate onin vitro lactate release and carbon dioxide production by brain of suckling rats

Wajner

Dutra

Cardoso

et al. 1991

J of Inher Metab Disea

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“…Glucose was measured in the medium before and after incubation by the glucose oxidase method [35]. Glucose uptake was determined by subtracting the amount after incubation from the total amount measured before incubation [36]. In some experiments, the NMDA antagonist MK-801 (10 lM) was used alone or in the presence of 5 mM Leu.…”

Section: Glucose Uptakementioning

confidence: 99%

Inhibition of Brain Energy Metabolism by the Branched-chain Amino Acids Accumulating in Maple Syrup Urine Disease

et al. 2007

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In the present work we investigated the in vitro effect of the branched-chain amino acids (BCAA) accumulating in maple syrup urine disease (MSUD) on some parameters of energy metabolism in cerebral cortex of rats. 14CO2 production from [1-14C]acetate, [1-5-14C]citrate and [U-14C]glucose, as well as glucose uptake by the brain were evaluated by incubating cortical prisms from 30-day-old rats in the absence (controls) or presence of leucine (Leu), valine (Val) or isoleucine (Ile). All amino acids significantly reduced 14CO2 production by around 20-55%, in contrast to glucose utilization, which was significantly increased by up to 90%. Furthermore, Leu significantly inhibited the activity of the respiratory chain complex IV, whereas Val and Ile markedly inhibited complexes II-III, III and IV by up to 40%. We also observed that trolox (alpha-tocopherol) and creatine totally prevented the inhibitory effects provoked by the BCAA on the respiratory chain complex activities, suggesting that free radicals were involved in these effects. The results indicate that the major metabolites accumulating in MSUD disturb brain aerobic metabolism by compromising the citric acid cycle and the electron flow through the respiratory chain. We presume that these findings may be of relevance to the understanding of the pathophysiology of the neurological dysfunction of MSUD patients.

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“…Glucose was measured in the medium before and after incubation by the glucose oxidase method (Trinder, 1969). Glucose uptake was determined by subtracting the amount after incubation from the total amount measured before incubation (Dutra et al, 1991). Glucose uptake was calculated as µmol of glucose h −1 g of tissue −1 and expressed as percentage of controls.…”

Section: Glucose Uptakementioning

confidence: 99%

Kynurenines Impair Energy Metabolism in Rat Cerebral Cortex

et al. 2006

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Growing evidence indicates that some metabolites derived from the kynurenine pathway, the major route of L-tryptophan catabolism, are involved in the neurotoxicity associated with several brain disorders, such as Huntington's disease, Parkinson's disease and Alzheimer's disease, as well as in glutaryl-CoA dehydrogenase deficiency (GAI). Considering that the pathophysiology of the brain damage in these neurodegenerative disorders is not completely defined, in the present study, we investigated the in vitro effect of L-kynurenine (Kyn), kynurenic acid (KA), 3-hydroxykynurenine (3HK), 3-hydroxyanthranilic acid (3HA) and anthranilic acid (AA) on some parameters of energy metabolism, namely glucose uptake, 14CO2 production from [U-14C] glucose, [1-14C] acetate and [1,5-14C] citrate, as well as on the activities of the respiratory chain complexes I-IV and Na+,K+-ATPase activity in cerebral cortex from 30-day-old rats. We observed that all compounds tested, except L-kynurenine, significantly increased glucose uptake and inhibited 14CO2 production from [U-14C] glucose, [1-14C] acetate and [1,5-14C] citrate. In addition, the activities of complexes I, II and IV of the respiratory chain were significantly inhibited by 3HK, while 3HA inhibited complexes I and II activities and AA inhibited complexes I-III activities. Moreover, Na+,K+-ATPase activity was not modified by these kynurenines. Taken together, our present data provide evidence that various kynurenine intermediates provoke impairment of brain energy metabolism.

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Effects of methylmalonate and propionate on uptake of glucose and ketone bodies in vitro by brain of developing rats

Cited by 25 publications

References 12 publications

Effect of methylmalonate onin vitro lactate release and carbon dioxide production by brain of suckling rats

Effect of methylmalonate onin vitro lactate release and carbon dioxide production by brain of suckling rats

Inhibition of Brain Energy Metabolism by the Branched-chain Amino Acids Accumulating in Maple Syrup Urine Disease

Kynurenines Impair Energy Metabolism in Rat Cerebral Cortex

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