Stimulation of pyruvate carboxylation by gastric secretagogues

Pyruvate carboxylation was stimulated by 2 gastric secretagogues, histamine and dibutyryl cyclic AMP, and by butyrate. Thiocyanate, an inhibitor of acid secretion, produced a slight decrease. Avidin significantly reduced acid secretion and this effect was overcome by biotin and oxalacetate. The results suggest that carboxylation of pyruvate is one of the reactions controlling oxidative metabolism and acid secretion in toad gastric mucosa.     

Stimulation of pyruvate carboxylation by gastric secretagogues

Summary Pyruvate carboxylation was stimulated by 2 gastric secretagogues, histamine and dibutyryl cyclic AMP, and by butyrate. Thiocyanate, an inhibitor of acid secretion, produced a slight decrease. Avidin significantly reduced acid secretion and this effect was overcome by biotin and oxalacetate. The results suggest that carboxylation of pyruvate is one of the reactions controlling oxidative metabolism and acid secretion in toad gastric mucosa.This investigation was supported by Consejo de Desarrollo Científico y Humanístico de la Universidad del Zulia, and by CONICIT Grant S1-0455.     

Light stimulated 'shunt-metabolism' succinate-alpha-ketoglutarate-isocitrate cycle and accumulation of citric acid in Aspergillus niger.

Studies with light of the visible range had shown that light plays significant role in the biosynthesis and accumulation of citric acid in Aspergillus niger. Accumulation of 14C-labelled carbon atoms in alpha-ketoglutaric, isocitric, succinic and glycolic acids in the cultures grown under illumination suggest a probable 'shunt-metabolism' leading to the succinate-alpha-ketoglutarate-isocitrate (SKI) cycle. This shunt metabolism minimizes the accumulation of citric acid in cultures due to depletion of intermediates.     

Purine nucleotide cycle as a possible anaplerotic process in rat skeletal muscle

Summary The intermediates of the purine nucleotide cycle (PNC) stimulated pyruvate oxidation by isolated skeletal muscle mitochondria in a system containing mitochondria and cytosol from rat skeletal muscle. Thus, in skeletal muscle the PNC might be involved in the anaplerotic supply of tricarboxylic acid cycle intermediates.Acknowledgment. This work was supported by a grant from the Polish Academy of Science within the project MR II.1.2.4.     

Mitochondrial abnormalities in fibroblast line GM3093 defective in oxidative metabolism

Fibroblast line GM3093 deficient in the activity of the pyruvate dehydrogenase complex, was derived from a patient reported to have an inherited defect affecting the tricarboxylic acid cycle. Our results suggest a generalized defect consisting of few and abnormal mitochondria and low activities of all mitochondrial enzymes examined.     

Increased mitochondrial palmitoylcarnitine/carnitine countertransport by flavone causes oxidative stress and apoptosis in colon cancer cells

Cancer cell metabolism is characterized by limited oxidative phosphorylation in order to minimize oxidative stress. We have previously shown that the flavonoid flavone in HT-29 colon cancer cells increases the uptake of pyruvate or lactate into mitochondria, which is followed by an increase in O₂^−.. production that finally leads to apoptosis. Similarly, a supply of palmitoylcarnitine in combination with carnitine induces apoptosis in HT-29 cells by increasing the mitochondrial respiration rate. Here we show that flavone-induced apoptosis is increased more than twofold in the presence of palmitoylcarnitine due to increased mitochondrial fatty acid transport and the subsequent metabolic generation of O₂^−. in mitochondria is the initiating factor for the execution of apoptosis. Received 12 August 2005; received after revision 12 October 2005; accepted 14 October 2005     

The halophilic properties of pyruvate kinase from Vibrio costicola, a moderate halophile.

Pyruvate kinase from Vibrio costicola, a moderate halophile, appears to be adapted to functioning in the presence of salt. Its stability depends on the ionic strength of the medium. The amino acid composition resembles that of other halophilic enzymes. It is proposed that the halophilic pyruvate kinase utilizes preferentially the Mn++ cofactor which forms more stable complexes in the presence of physiological concentrations of salt.     

Der Atmungsquotient der Tabakblätter

Summary The respiration quotient (R Q) of the tobacco leaves is always higher than one. In contrast to that of the leaves of succulent plants it does not drop below unity during the night. From this it is concluded that the organic acids (malic, oxalic and citric acids), which serve as respiration substrate, cannot be related to the carbohydrate metabolism (tricarbon acid cycle). They must rather be considered as primary assimilation products or as related to the nitrogen metabolism (transamination of the primary assimilation product aspartic acid).     

Die Bedeutung der Mitochondrienstruktur für die Zitronensäuresynthese

Summary Rat liver mitochondria proved to need a structural integrity for optimal citric acid synthesis. Structural impairment leads to an inhibition of the synthetic activity of the mitochondria, the degree of inhibition being inversely related to substrate concentration; it causes, however, no inactivation of the condensing enzyme. The dependence of this reaction upon the structural conditions is the consequence of an interaction between the two mitochondrial enzymes acetyl-CoA deacylase and condensing enzyme.     

Folding and assembly defects of pyruvate dehydrogenase deficiency-related variants in the E1α subunit of the pyruvate dehydrogenase complex

The pyruvate dehydrogenase complex (PDC) bridges glycolysis and the citric acid cycle. In human, PDC deficiency leads to severe neurodevelopmental delay and progressive neurodegeneration. The majority of cases are caused by variants in the gene encoding the PDC subunit E1α. The molecular effects of the variants, however, remain poorly understood. Using yeast as a eukaryotic model system, we have studied the substitutions A189V, M230V, and R322C in yeast E1α (corresponding to the pathogenic variants A169V, M210V, and R302C in human E1α) and evaluated how substitutions of single amino acid residues within different functional E1α regions affect PDC structure and activity. The E1α A189V substitution located in the heterodimer interface showed a more compact conformation with significant underrepresentation of E1 in PDC and impaired overall PDC activity. The E1α M230V substitution located in the tetramer and heterodimer interface showed a relatively more open conformation and was particularly affected by low thiamin pyrophosphate concentrations. The E1α R322C substitution located in the phosphorylation loop of E1α resulted in PDC lacking E3 subunits and abolished overall functional activity. Furthermore, we show for the E1α variant A189V that variant E1α accumulates in the Hsp60 chaperonin, but can be released upon ATP supplementation. Our studies suggest that pathogenic E1α variants may be associated with structural changes of PDC and impaired folding of E1α.     

The halophilic properties of pyruvate kinase fromVibrio costicola,a moderate halophile

Summary Pyruvate kinase fromVibrio costicola, a moderate halophile, appears to be adapted to functioning in the presence of salt. Its stability depends on the ionic strength of the medium. The amino acid composition resembles that of other halophilic enzymes. It is proposed that the halophilic pyruvate kinase utilizes preferentially the Mn⁺⁺ cofactor which forms more stable complexes in the presence of physiological concentration of salt.     

Light stimulated ‘shunt-metabolism’ succinate-α-ketoglutarate-isocitrate cycle and accumulation of citric acid inAspergillus niger

Summary Studies with light of the visible range had shown that light plays a significant role in the biosynthesis and accumulation of citric acid inAspergillus niger. Accumulation of¹⁴C-labelled carbon atoms in -ketoglutaric, isocitric, succinic and glycolic acids in the cultures grown under illumination suggest a probable shunt-metabolism leading to the succinate--ketoglutarate-isocitrate (SKI) cycle. This shunt metabolism minimizes the accumulation of citric acid in cultures due to depletion of intermediates.Acknowledgment. The authors wish to express their gratitude to the International Atomic Energy Agency, Vienna, Austria, for the financial assistance.     

Mitochondrial abnormalities in fibroblast line GM3093 defective in oxidative metabolism

Summary Fibroblast line GM3093 deficient in the activity of the pyruvate dehydrogenase complex, was derived from a patient reported to have an inherited defect affecting the tricarboxylic acid cycle. Our results suggest a generalized defect consisting of few and abnormal mitochondria and low activities of all mitochondrial enzymes examined.Preliminary reports of aspects of this work appeared as abstracts in Trans. Am. Soc. Neurochem.15 (1984) 178, and Soc. Neurosci.10 (1984) 996.Developmental and Metabolic Neurology Branch.Surgical Neurology Branch.     

Oxydation von Bernsteinsäure durch Leber akut urämischer Ratten

Summary The oxydative desamination of amino acids in the liver of acute uremic rats is increased. Simultaneously the citric acid cycle in the liver of these rats is stimulated. It is suggested that the ketone-acids formed by the increased amino acid degradation are removed by the activated citric acid cycle.

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5. Mitteilung über Untersuchungen der Rest-N-fraktionen bei Urämie

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Die vorliegende Arbeit wurde mit Unterstützung des Schweizerischen Nationalfonds durchgeführt.     

Über die Grenzen der metabolischen Adaptationsfähigkeit vonAspergillus niger

Summary The ability ofA. niger to assimilate malonic acid, which we consider to be the way both of obtaining energy (citric acid cycle) and of synthesizing cell substances (glyoxylic acid cycle), is reduced by substitution. While methyl malonic acid is quickly assimilated and ethyl malonic acid more slowly propyl-, dimethyl-, and diethyl malonic acid cannot be used by already formed molds.     

Über den Intermediär-Stoffwechsel vonAspergillus niger

Summary Oxalic acid is only dissimilated if other carbon sources are present (e.g. citric acid, succinic acid), whereas malonic acid is also dissimilated as a single component byA. niger. It is supposed that the latter is used by the mould not only energetically but also for building up cell substance.     

Neuronal calcium signaling: function and dysfunction

Calcium (Ca²⁺) is an universal second messenger that regulates the most important activities of all eukaryotic cells. It is of critical importance to neurons as it participates in the transmission of the depolarizing signal and contributes to synaptic activity. Neurons have thus developed extensive and intricate Ca²⁺ signaling pathways to couple the Ca²⁺ signal to their biochemical machinery. Ca²⁺ influx into neurons occurs through plasma membrane receptors and voltage-dependent ion channels. The release of Ca²⁺ from the intracellular stores, such as the endoplasmic reticulum, by intracellular channels also contributes to the elevation of cytosolic Ca²⁺. Inside the cell, Ca²⁺ is controlled by the buffering action of cytosolic Ca²⁺-binding proteins and by its uptake and release by mitochondria. The uptake of Ca²⁺ in the mitochondrial matrix stimulates the citric acid cycle, thus enhancing ATP production and the removal of Ca²⁺ from the cytosol by the ATP-driven pumps in the endoplasmic reticulum and the plasma membrane. A Na⁺/Ca²⁺ exchanger in the plasma membrane also participates in the control of neuronal Ca²⁺. The impaired ability of neurons to maintain an adequate energy level may impact Ca²⁺ signaling: this occurs during aging and in neurodegenerative disease processes. The focus of this review is on neuronal Ca²⁺ signaling and its involvement in synaptic signaling processes, neuronal energy metabolism, and neurotransmission. The contribution of altered Ca²⁺ signaling in the most important neurological disorders will then be considered.     

Der Einfluss von 2-Deoxy-D-glucose auf die Substratoxydation in Ascites-Tumorzellen

Summary The effect of the glycolytic inhibitor 2-deoxy-D-glucose on the oxidation of¹⁴C-labelled substrates of the tricarboxylic acid cycle was investigated in ascites carcinoma cells of the mouse. In the presence of high concentrations of glucose, deoxyglucose stimulates the oxidation of pyruvate C-2 and C-3 to CO₂, but not the oxidation of succinate C-1,4 to CO₂. While deoxyglucose causes, in the absence of glucose, an inhibition of the oxidation of exogenous palmitate C-1 to CO₂, it causes, in the presence of glucose, a stimulation of the palmitate oxidation. There is a possible correlation between the effect of deoxyglucose on the intracellular ATP metabolism and the effect of deoxyglucose on the palmitate oxidation.