Der Kohlenhydratstoffwechsel des Gehirns nach Blockade des Pentose-Phosphat-Weges durch 6-Aminonicotinsäureamid

Lange, Klaus; Kolbe, H.; Keller, Konrad; Herken, H.

doi:10.1515/bchm2.1970.351.2.1241

Cited by 61 publications

(11 citation statements)

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“…There is no firm evidence to support this suggestion, either from subsequent work in vivo (Kauffman and Johnson, 1974) or in vitro, which showed no significant increase in the concentration of glucose 6-phosphate (Hothersall et al, 1981). Moreover, the absence of a consistent and significant change in the concentration of fructose phosphate in vivo Lange et al, 1970;Kauffman and Johnson, 1974) and phosphoglycerate in vivo (Lange et al, 1970) or in the extent of labelling of phosphoglycerate in vivo after injection of [U-14C]glucose, reported in the present investigation, makes it unlikely that phosphoglucoisomerase was uniquely involved in slowing glucose metabolism via the Embden-Meyerhof pathway in the brain of 6-AN-treated rats.…”

Section: The Role Of the Hexosemonophosphate Shunt In Brainmentioning

confidence: 89%

“…This observation is in agreement with the original findings of and supports the view that the primary action of 6-AN is the inhibition of 6-phosphogluconate dehydrogenase. The experimental evidence showed that no other enzyme, either dependent on NAD and NADP or otherwise, involved in the metabolism of glucose was inhibited as intensely as the 6-phosphogluconate dehydrogenase (Lange et al, 1970). In addition, by confirming the finding of a dose-dependent increase in the concentration of 6-phosphogluconate in the brain of 6-aminonicotinamide-treated mice (Kauffman and Johnson, 1974), the results of the present investigation gave evidence that the concentrations of glucose and glucose 6-phosphate in the brain were also dose-dependent in 6-AN-treated rats.…”

Section: Inhibition Of the Hexosemonophosphate Shuntmentioning

confidence: 99%

“…2 in the glucose unit of cerebral glycogen, the estimated contribution of the hexosemonophosphate shunt t o the overall glucose utilization was 2.9% in the adult rat brain (Hostetler and Landau, 1967), and 543% in monkey brain stem, cerebellum, hemispheres, and hypothalamus (Hostetler et al, 1970). In the present investigation a direct method was used for the measurement of the rate of utilization of glucose via the hexosemonophosphate shunt. The method is based on the observation that 6-phosphogluconate dehydrogenase in rat brain is selectively inhibited by administration of 6-aminonicotinamide Lange et al, 1970).…”

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confidence: 99%

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The Rate of Utilization of Glucose Via Hexosemonophosphate Shunt in Brain

Gaitonde

Evison

Evans

1983

Journal of Neurochemistry

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The concentration of 6-phosphogluconate in the brain increased from 0-24 nmol/g in the controls to 1430 and 1506 nmol/g in rats treated with 50 mg of 6-aminonicotinamide/kg of body weight. A dose-dependent increase in the concentrations of glucose and glucose 6-phosphate as well as of 6-phosphogluconate was found in the brains of 6-aminonicotinamide-treated rats. The biochemical changes and symptoms of neurological disorder in 6-aminonicotinamide-treated rats were not due to hypothermia. The rate of utilization of glucose via the hexosemonophosphate shunt was determined by isolation of gluconate from 6-phosphogluconate and measurement of its [14C]content at short time intervals after injection of [U-14C]glucose into 6-aminonicotinamide-treated rats; it was 16.5 nmol of glucose utilized/min per g of brain, and represented approximately 2.3% of the overall utilization of glucose in the brain. A highly significant correlation was observed between the concentration of 6-phosphogluconate and the concentration of glucose 6-phosphate and free glucose. The validity of this correlation was supported by the results of previous investigations involving several other treatments.

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Section: The Role Of the Hexosemonophosphate Shunt In Brainmentioning

confidence: 89%

Section: Inhibition Of the Hexosemonophosphate Shuntmentioning

confidence: 99%

mentioning

confidence: 99%

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The Rate of Utilization of Glucose Via Hexosemonophosphate Shunt in Brain

Gaitonde

Evison

Evans

1983

Journal of Neurochemistry

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“…Changes that occur in the neural glycolytic pathway of 6-aminonicotinamide-treated animals have been related to a secondary inhibition of phosphoglucoisomerase, which is known to be inhibited by relatively low concentrations of 6-phosphogluconate. Production of lactate and utilization of glycogen during ischemia were reduced in brains from 6-aminonicotinamide-treated mice, according to the suggestion that glycolysis is inhibited in cerebral tissue by this agent [Kahana et al, 1960;Kohler et al, 1970;Lange et al, 1970;Kauffman and Johnson, 19741. Calcium hopantenate (calcium salt of homopantothenic acid) possesses a low antagonistic action against pantothenic acid.…”

Section: Introductionmentioning

confidence: 99%

Cerebral endogenous substrate utilization during the recovery period after profound hypoglycemia

Benzi

Villa

Dossena

et al. 1984

J of Neuroscience Research

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Markedly decreased levels of energy-rich phosphates were seen in cerebral cortex after severe hypoglycemia, followed by their partial restitution during the recovery period. During hypoglycemia the nonglucose endogenous substrates were provided by glycolytic intermediates, by Krebs cycle intermediates, and by related amino acids. Other potential substrates for brain oxidation were provided by the breakdown of phospholipids and fatty acids. After a 20-min period of posthypoglycemic recovery, partial restoration of carbohydrates and amino acids occurred, although the amino acid pool size was still reduced. The alterations in phospholipids and fatty acids persisted, while there was a tendency toward normalization of the free fatty acid content. During the posthypoglycemic recovery, treatment with some specific metabolic modulators (6-aminonicotinamide, hopantenate, uridine, L-acetylcarnitine) suggested the possibility of an alternative cerebral substrate utilization owing to modulation of the cerebral biochemical machinery. Thus, increased carbohydrate utilization by hopantenate was consistent with decreased lipid breakdown, while increased carbohydrate utilization by uridine was concomitant with decreased amino acid degradation. In this way, decreased cerebral carbohydrate utilization by 6-amino-nicotinamide was associated with increased lipid and amino acid breakdown. Furthermore, the increased loss of cerebral phospholipids and phospholipid-bound fatty acids by L-acetylcarnitine occurred in the presence of a large glucose availability and was associated with an extensive reduction of cerebral glycolytic flux.

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“…2B). Presence of the 6‐phosphogluconate dehydrogenase inhibitor 6‐aminonicotinamide (6AN; Lange et al, 1970) increased the cellular GSSG content to about 60% of GSx after exposure to sustained peroxide stress (Fig. 2B) while exacerbating the peroxide‐induced decrease in GSx (Fig.…”

Section: Resultsmentioning

confidence: 99%

Sustained hydrogen peroxide stress decreases lactate production by cultured astrocytes

Liddell

Zwingmann

Schmidt

et al. 2009

J of Neuroscience Research

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Oxidative stress and disrupted energy metabolism are common to many pathological conditions of the brain. Because astrocytes play an important role in the glucose metabolism of the brain, we have investigated whether sustained oxidative stress affects astroglial glucose metabolism with cultured primary rat astrocytes as a model system. Cultured astrocytes were exposed to a sustained concentration of approximately 50 muM H(2)O(2) in the presence of [U-(13)C]glucose, and cellular and extracellular contents of lactate and glucose were analysed by enzymatic assays and NMR spectroscopy. Exposure of the cells to sustained H(2)O(2) stress for up to 120 min significantly lowered the rate of lactate accumulation in the media to 61% +/- 14% of that in cultures incubated without peroxide. In addition, the ratio of lactate release to glucose consumption was lowered in peroxide-treated astrocytes to 77% +/- 13% of that in control cells, and the specific activity of glyceraldehyde-3-phosphate dehydrogenase had declined to about 10% of control cells within 90 min. In addition, the (13)C enrichment of intracellular and extracellular [(13)C]lactate was about 30% and 95%, respectively, and was not affected by the presence of peroxide, demonstrating that two metabolic pools of lactate are present in cultured astrocytes. The decreased rate of lactate production by astrocytes that have been exposed to peroxide stress is a new example of an alteration by oxidative stress of an important metabolic pathway in astrocytes. Such alterations could contribute to the pathological conditions that have been connected with oxidative stress and disrupted energy metabolism in the brain.

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Der Kohlenhydratstoffwechsel des Gehirns nach Blockade des Pentose-Phosphat-Weges durch 6-Aminonicotinsäureamid

Cited by 61 publications

References 1 publication

The Rate of Utilization of Glucose Via Hexosemonophosphate Shunt in Brain

The Rate of Utilization of Glucose Via Hexosemonophosphate Shunt in Brain

Cerebral endogenous substrate utilization during the recovery period after profound hypoglycemia

Sustained hydrogen peroxide stress decreases lactate production by cultured astrocytes

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