Paths of carbon in gluconeogenesis and lipogenesis: the role of mitochondria in supplying precursors of phosphoenolpyruvate.

Lardy, Henry A.; Paetkau, Verner; Walter, Paul

doi:10.1073/pnas.53.6.1410

Cited by 198 publications

(44 citation statements)

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“…Attempts of Krebs et al [3] to obtain gluconeogenesis in liver homogenates from rats and several other species were not successful and this system as well as the one of Mendicino and Utter [2] has not been used for further studies. Beside these investigations on the whole chain of gluconeogenesis in cellfree systems, some studies on partial sequences in subcellular fractions of rat liver have been made by the group of Lardy [8,9], by McDermott and Veneziale [lo] and by ourselves Recently, liver cells rendered permeable to substrates and effectors by treatment with filipin were proposed as a possible [I 1,121. model for studying metabolic regulation by low molecular weight compounds [13]. A different approach to the same problem is described in the present study which demonstrates the conversion of malate to glucose 6-phosphate at rates comparable to those observed in rat hepatocytes in a cell-free system derived from rat liver.…”

mentioning

confidence: 99%

Gluconeogenesis in vitro

Mörikofer‐Zwez

Stoecklin

Walter

1982

European Journal of Biochemistry

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A cell-free system prepared from rat liver containing cytosol and mitochondria as well as a number of cofactors at near physiological concentrations was shown to form glucose 6-phosphate from malate + 3-phosphoglycerate at a rate of 1.11 0.09 pmol . min-' . g liver-' (mean f SEM, n = 9, 30°C). At least 70% of glucose 6-phosphate formed was derived from malate as calculated from experiments with [U-14C]malate. The indicated rates were measured between 10 min and 30 min incubation time when the system was near steady state with respect to the lactate/pyruvate ratio and to most of the gluconeogenic intermediates.In the absence of mitochondria, the rate of formation of glucose 6-phosphate from malate was about seven times lower than in their presence. A comparison between incubations carried out in presence or absence of mitochondria revealed that mitochondria decreased the lactate/pyruvate ratio and increased the ratio of (ATP + ITP)/(ADP + IDP). It could be shown that under the present incubation conditions, formation of glucose 6-phosphate was closely linked to the ratio of (ATP + ITP)/(ADP + IDP) whereas changing redox ratios had little influence on the gluconeogenic rate.Regulation of gluconeogenesis in liver is known to involve mitochondrial, cytosolic as well as microsomal reactions and has mainly been studied in liver slices, perfused liver or hepatocytes (for a review see [I]). Two early attempts have, however, been made to set up gluconeogenic systems which are readily accessible to low molecular weight effectors in order to obtain more detailed information on regulatory mechanisms. Mendicino and Utter [2] showed that a recombination of purified gluconeogenic enzymes was able to form glucose 6-phosphate from 3-phosphoglycerate or fumarate in the presence of chicken liver mitochondria. Furthermore, the group of Krebs [3,4] described a cell-free system of pigeon liver homogenate which formed glucose from lactate at physiological rates. In both cases, systems were employed where phosphoenolpyruvate carboxykinase is localized within the mitochondria [S,6] which is not the case in rat liver [7]. Attempts of Krebs et al. [3] to obtain gluconeogenesis in liver homogenates from rats and several other species were not successful and this system as well as the one of Mendicino and Utter [2] has not been used for further studies. Beside these investigations on the whole chain of gluconeogenesis in cellfree systems, some studies on partial sequences in subcellular fractions of rat liver have been made by the group of Lardy [8,9], by McDermott and Veneziale [lo] and by ourselves Recently, liver cells rendered permeable to substrates and effectors by treatment with filipin were proposed as a possible [I 1,121. model for studying metabolic regulation by low molecular weight compounds [13]. A different approach to the same problem is described in the present study which demonstrates the conversion of malate to glucose 6-phosphate at rates comparable to those observed in rat hepatocytes in a cell-free system derive...

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mentioning

confidence: 99%

Gluconeogenesis in vitro

Mörikofer‐Zwez

Stoecklin

Walter

1982

European Journal of Biochemistry

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“…Furthermore, the reciprocal changes in aspartate and glutamate observed in livers from Prkce −/− mice are consistent with increased production of oxaloacetate for gluconeogenesis by aspartate transamination, which also produces glutamate [7]. We therefore examined whether diet-and PKCε-dependent changes in amino acids were reflected in alterations in gluconeogenesis.…”

Section: Resultsmentioning

confidence: 94%

Deletion of protein kinase Cε in mice has limited effects on liver metabolite levels but alters fasting ketogenesis and gluconeogenesis

et al. 2012

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Aims/hypothesis Protein kinase Cε (PKCε) is emerging as a key mediator of lipid-induced insulin resistance in liver and hepatic lipid metabolism itself. We investigated whether PKCε plays a role in other metabolic processes, to further examine its suitability as a therapeutic target. Methods We measured amino acid, organic acid and sugar levels by liquid and gas chromatography-mass spectrometry of liver extracts from chow and fat-fed wild-type (WT) and PKCε-deficient (Prkce −/− ) mice. Fed and fasting glucose, ketone and fatty acid levels were measured in blood. Triacylglycerol levels and gluconeogenic and ketogenic enzyme expression were measured in liver.The effect of fasting on epididymal fat pad mass was also determined.Results Metabolomic analysis indicated that the short-term high-fat diet affected over 20 compounds, including a 50% reduction in the glucogenic amino acid alanine. Prkce deletion resulted only in a reduction of 4-hydroxyproline and aspartate and an increase in glutamate. However, upon fasting, Prkce −/− mice were better able to maintain blood glucose levels and also exhibited lower levels of the ketone β-hydroxybutyrate compared with WT mice. Upon fasting, Prkce deletion also resulted in lower liver and plasma lipids and a smaller reduction in fat pad mass. Conclusions/interpretation Metabolomic analysis provided new insights into the effects of a high-fat diet on liver metabolite levels. Glucose homeostasis under fasting conditions is improved in Prkce −/− mice, which, in turn, may reduce the mobilisation of lipid from adipose tissue, reducing the availability of ketogenic substrate in the liver. Together with the protection against fat-diet-induced glucose intolerance previously observed in the fed state, these findings indicate PKCε as a unique therapeutic target for the improvement of glucose homeostasis.Keywords Alanine . Gluconeogenesis .

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“…The Gram-negative bacterial cell wall is a complex structure and its carbohydrate composition can be modified qualitatively by modifying the carbohydrates present in the growth medium (Weidel, Frank & Martin, 1960;Nikaido, 1962). Lactate has been shown to be a precursor of carbohydrates (Krebs, Dierks & Gascoyne, 1964;Lardy, Paetkau & Walter, 1965) and therefore, has the potential of causing such modifications in the cell-wall composition of Haemophilus injluenzae. In addition, competence can be destroyed with sodium periodate (Ranhand & Lichstein, 1966).…”

Section: Results a N D Discussionmentioning

confidence: 99%

Specificity of Lactate for the Development of Competence in Haemophilus influenzae

Ranhand¹

1970

Journal of General Microbiology

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SUMMARYA number of common carbohydrates and polyols were tested to see if they could replace the lactate requirement for the development of competence in cultures of Haemophilus injluenzae. Pyruvate, fructose, and glucose, when tested in the presence of inosine, were slightly stimulatory. They gave respectively, 29, 25 and 13 % of the control value obtained with inosine and lactate. Under similar test conditions, mannose, mannitol, galactose, sorbose, sorbitol, ribose, glucosamine, rhamnose, D (-) arabinose, L (+) arabinose, xylose and fucose were inactive.In combination experiments, glucose, inosine and pyruvate, and fructose, inosine and pyruvate stimulated the development of competence to 50 to 70 % of the inosine and lactate control value. Without inosine, the stimulation due to glucose and pyruvate, and fructose and pyruvate was 3 and 9 %, respectively.

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Paths of carbon in gluconeogenesis and lipogenesis: the role of mitochondria in supplying precursors of phosphoenolpyruvate.

Cited by 198 publications

References 17 publications

Gluconeogenesis in vitro

Gluconeogenesis in vitro

Deletion of protein kinase Cε in mice has limited effects on liver metabolite levels but alters fasting ketogenesis and gluconeogenesis

Specificity of Lactate for the Development of Competence in Haemophilus influenzae

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