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PubMed1978

Pyruvate metabolism after in vivo exposure to oral arsenic.

This study investigated altered pyruvate metabolism after prolonged oral arsenic exposure. Male rats were given access to deionized drinking water containing 0, 40 or 85 ppm sodium arsenate (As5+) for 3 weeks. Respiration studies with mitochondria isolated from treated animals indicated decreased state 3 respiration (with ADP) and decreased respiratory control ratios (RCR) for pyruvate/malate-mediated respiration, but not for succinate-mediated respiration, as compared to control respiration values. In addition, pyruvate dehydrogenase activity was measured, in both liver and intestine, before and after Mg-activation in vitro. After 3 weeks, the effects of arsenic at the highest dose level were pronounced on the basal pyruvate dehydrogenase activity (before activation) as well as the total pyruvate dehydrogenase (after activation). The inhibition of pyruvate dehydrogenase activity both before and after Mg-activation suggests an arsenic effect on mitochondrial pyruvate metabolism which, in part, involves inhibition of pyruvate decarboxylase. Evidence is also presented which may indicate an arsenic effect on the kinase and/or phosphatase which regulate pyruvate dehydrogenase activity.

Animals↗
PubMed1987

"Pyruvate recycling" and its influence on the estimation of the pentose pathway in intact liver and Morris hepatoma 5123TC cells.

The phenomenon of "pyruvate recycling" is demonstrated in perfused rat liver, rabbit liver in situ and in Morris Hepatoma 5123TC cells and quantitatively measured using [2-14C]pyruvate and the method of Friedmann et al. (1971). Various metabolites, viz. lactate, DHAP, glucose, glucose 6-P and fructose 6-P were isolated and degraded following the metabolism of [2-14C]pyruvate and [2-14C]glycerol in order to assess the 14C-distributions imparted by "pyruvate recycling" reactions. The labelling of DHAP, lactate, glucose and glucose 6-P showed 14C randomizations consistent with the operation and the quantitative extent of "pyruvate recycling". These findings support the proposal that the actions of "pyruvate recycling" may account for the failure to find significant levels of 14C isotope at C-1 of glucose 6-P following the metabolism of [4,5,6-14C]- or [6-14C]glucose by L-type pentose pathway metabolism in aerobic intact tissues. "Pyruvate recycling" diminishes the measured value of the L-type pentose cycle in intact tissues and qualifies one of the mechanistic predictions of the L-type pentose pathway which was unravelled by tracing its reactions with labelled ribose 5-P and liver enzymes (Horecker et al., 1954; Williams et al., 1978a,b) in vitro. The demonstration of an association of L-type pentose pathway reactions with "pyruvate recycling" by way of the common reactions of their triose-P intermediates qualifies the superficial acceptance of the predictions of the L-type pathway in vitro for the distribution of isotopic labels by aerobic tissues in vivo.

Animals↗
PubMed1993

Indole-pyruvic acid treatment reduces damage in striatum but not in hippocampus after transient forebrain ischemia in the rat.

The effects of treatment with indole-pyruvic acid, an endogenous metabolite of tryptophan converted into kynurenic acid in the brain, were studied in rats after transient forebrain ischemia induced by the 4-vessel occlusion procedure. The histological analysis showed a significant protective effect of indole-pyruvic acid treatment on striatal ischemic lesions assessed by the extent of regional atrophy and the area of neuronal disappearance 14 days after ischemia. Striatal neurons were labelled by dopamine and adenosine 3':5' monophosphate regulated phosphoprotein-32 immunoreactivity. Conversely, increased neuronal loss, regional atrophy and glial fibrillary acidic protein immunoreactivity, an index of post-injury astroglial activation, were observed in the hippocampal formation, especially the CA3 field, of indole-pyruvic acid-treated rats when compared with vehicle-treated ischemic rats. The treatment with indole-pyruvic acid did not produce any improving effects in a test assessing short-term impairments after transient ischemia (motor test score at 24 h and 48 h post-ischemia). Furthermore, no significant effects of indole-pyruvic acid treatment were found on performance in water T-maze studied at 7 and 14 days post-ischemia. The opposite effects of indole-pyruvic acid on ischemic lesion in different brain regions may be related to its multiple neurochemical actions in the brain. The protective effect of indole-pyruvic acid on ischemic damage in striatum may be due to its conversion into kynurenic acid, a broad spectrum glutamate receptor antagonist. At hippocampal level, where glutamate receptor antagonists have been proved ineffective in the present lesion model, indole-pyruvic acid-induced changes in monamine availability may lead to a worsening of neuronal damage.

Animals↗
PubMed1987

Effects of insulin on perfused liver from streptozotocin-diabetic and untreated rats: 13C NMR assay of pyruvate kinase flux.

The effects of insulin in vitro on perfused liver from streptozotocin-diabetic rats and their untreated littermates during gluconeogenesis from either [3-13C]alanine + ethanol or [2-13C]pyruvate + NH4Cl + ethanol were studied by 13C NMR. A 13C NMR determination of the rate of pyruvate kinase flux under steady-state conditions of active gluconeogenesis was developed; this assay includes a check on the reuse of recycled pyruvate. The preparations studied provided gradations of pyruvate kinase flux within the confines of the assay's requirement of active gluconeogenesis. By this determination, the rate of pyruvate kinase flux was 0.74 +/- 0.04 of the gluconeogenic rate in liver from 24-h-fasted controls; in liver from 12-h-fasted controls, relative pyruvate kinase flux increased to 1.0 +/- 0.2. In diabetic liver, this flux was undetectable by our NMR method. Insulin's hepatic influence in vitro was greatest in the streptozotocin model of type 1 diabetes: upon treatment of diabetic liver with 7 nM insulin in vitro, a partial reversal of many of the differences noted between diabetic and control liver was demonstrated by 13C NMR. A major effect of insulin in vitro upon diabetic liver was the induction of a large increase in the rate of pyruvate kinase flux, bringing relative and absolute fluxes up to the levels measured in 24-h-fasted controls. By way of comparison, the effects of ischemia on diabetic liver were studied by 13C NMR to test whether changes in allosteric effectors under these conditions could also increase pyruvate kinase flux. A large increase in this activity was demonstrated in ischemic diabetic liver.

Alanine↗
PubMedDate not supplied

Nonlinear dynamics of eucaryotic pyruvate dehydrogenase multienzyme complex: decarboxylation rate, oscillations, and multiplicity.

Pyruvate conversion to acetyl-CoA by the pyruvate dehydrogenase (PDH) multienzyme complex is known as a key node in affecting the metabolic fluxes of animal cell culture. However, its possible role in causing possible nonlinear dynamic behavior such as oscillations and multiplicity of animal cells has received little attention. In this work, the kinetic and dynamic behavior of PDH of eucaryotic cells has been analyzed by using both in vitro and simplified in vivo models. With the in vitro model the overall reaction rate (nu(1)) of PDH is shown to be a nonlinear function of pyruvate concentration, leading to oscillations under certain conditions. All enzyme components affect nu(1) and the nonlinearity of PDH significantly, the protein X and the core enzyme dihydrolipoamide acyltransferase (E2) being mostly predominant. By considering the synthesis rates of pyruvate and PDH components the in vitro model is expanded to emulate in vivo conditions. Analysis using the in vivo model reveals another interesting kinetic feature of the PDH system, namely, multiple steady states. Depending on the pyruvate and enzyme levels or the operation mode, either a steady state with high pyruvate decarboxylation rate or a steady state with significantly lower decarboxylation rate can be achieved under otherwise identical conditions. In general, the more efficient steady state is associated with a lower pyruvate concentration. A possible time delay in the substrate supply and enzyme synthesis can also affect the steady state to be achieved and leads to oscillations under certain conditions. Overall, the predictions of multiplicity for the PDH system agree qualitatively well with recent experimental observations in animal cell cultures. The model analysis gives some hints for improving pyruvate metabolism in animal cell culture.

Acetyl Coenzyme A↗
PubMed1982

Influence of pyruvate on ammonia metabolism by renal cortical mitochondria.

The effect of the tricarboxylic acid (TCA) cycle precursor, pyruvate, on glutamine metabolism by isolated renal cortical mitochondria was assessed by quantitating its key nitrogen and carbon metabolites. When mitochondria from normal rats were incubated at pH 7.4, pyruvate (2 mM) inhibited ammonia production by almost completely erradicating glutamate deamination and by diminishing glutamine deamidation but to a lesser extent. Alpha KG, citrate, and malate accumulation in the incubation medium were increased dramatically reflecting the increased flux of pyruvate through the TCA cycle; the intramitochondrial concentrations of both Alpha KG and glutamate were increased. Thus, pyruvate primarily inhibits flux through glutamate dehydrogenase as a result either of an increase in Alpha KG concentration and/or a decrease in the redox (NAD/NADH) potential secondary to enhanced flux through the TCA cycle. Glutamine deamidation is secondarily inhibited, presumably due to the increased intramitochondrial concentration of glutamate. Citrate (2 mM) produced changes comparable to those observed with pyruvate. Mitochondria from normal rats incubated at pH 7.0 as well as mitochondria from rats with chronic metabolic acidosis responded to pyruvate in a fashion qualitatively similar to normal mitochondria incubated at pH 7.4. Glutamate deamination was inhibited significantly, but a high rate persisted with chronic acidosis despite the presence of pyruvate. Nevertheless, when glutamine metabolism was contrasted with normal mitochondria incubated at pH 7.4, the response to in vitro incubation in an acid pH as well as to chronic metabolic acidosis was similar quantitatively regardless of whether glutamine alone or in combination with pyruvate was present in the incubation medium.

Acidosis↗
PubMed1978

Pyruvate carboxylase from a thermophilic Bacillus. Studies on the specificity of activation by acyl derivatives of coenzyme A and on the properties of catalysis in the absence of activator.

1. Oxaloacetate synthesis catalysed by pyruvate carboxylase from a thermophilic Bacillus in the absence of acetyl-CoA required addition of high concentrations of pyruvate, MgATP(2-) and HCO(3) (-), and at 45 degrees C occurred at a maximum rate approx. 20% of that in the presence of a saturating concentration of acetyl-CoA. The apparent K(m) for HCO(3) (-) at pH7.8 was 400mm without acetyl-CoA, and 16mm with a saturating activator concentration. The relationship between reciprocal initial rate and reciprocal MgATP(2-) concentration was non-linear (convex-down) in the absence of acetyl-CoA, but the extent of deviation decreased as the activator concentration was increased. The relationship between reciprocal initial rate and reciprocal pyruvate concentration was non-linear (convex-down) in the presence or absence of acetyl-CoA. 2. The optimum pH for catalysis of oxaloacetate synthesis was similar in the presence or absence of acetyl-CoA. The variation with pH of apparent K(m) for HCO(3) (-) implicated residue(s) with pK(a) 8.6 in catalysis of the activator-independent oxaloacetate synthesis. 3. Linear Arrhenius and van't Hoff plots were observed for the temperature-dependence of oxaloacetate synthesis in the absence of acetyl-CoA over the range 25-55 degrees C. E(a) (activation energy) was 56.3kJ/mol and DeltaH(double dagger) (HCO(3) (-)) (enthalpy of activation) was -38.6kJ/mol. In the presence of acetyl-CoA, biphasic Arrhenius and van't Hoff plots are observed with a change of slope at 30 degrees C in each case. E(a) was 43.7 and 106.3kJ/mol above and below 30 degrees C respectively. 4. Incubation of Bacillus pyruvate carboxylase with trinitrobenzenesulphonate caused specific inactivation of acetyl-CoA-dependent catalytic activity associated with the incorporation of 1.3+/-0.2 trinitrophenyl residues per subunit. Activator-independent catalysis and regulatory inhibition by l-aspartate were unaffected. The rate of inactivation of acetyl-CoA-dependent catalysis by trinitrobenzenesulphonate was specifically decreased by addition of acetyl-CoA and other acetyl-CoA and other acyl-CoA species, but complete protection was not obtained. 5. All alkylacyl derivatives of CoA tested activated Bacillus pyruvate carboxylase; acetyl-CoA was the most effective. The apparent K(a) exhibited a biphasic relationship with acyl-chain length for the straight-chain homologues. Certain long-chain acyl-CoA species showed additional activation at a high concentration. Weak activation occurred on addition of CoA or adenosine 3',5'-bisphosphate, but carboxyacyl-CoA species and derivatives containing a modified phosphoadenosyl group were inhibitory. Thioesters of CoA with non-carboxylic acids, e.g. methanesulphonyl-CoA, serve as activators of the thermophilic Bacillus and Saccharomyces cerevisiae pyruvate carboxylases, but as inhibitors of pyruvate carboxylases obtained from chicken and rat liver. 6. alpha-Oxoglutarate mimics the effect of l-aspartate as a regulatory inhibitor of the pyruvate carboxylases from both the thermophilic Bacillus and Saccharomyces cerevisiae. l-Glutamate was ineffective in both cases.

Acetyl Coenzyme A↗
PubMed1985

Influence of lesions in the limbic-hypothalamic system on metabolic response of pyruvate to daily repeated cold exposure in rabbits.

The effects of lesions of the limbic-hypothalamic structures on the pyruvate metabolic responses to daily repeated cold exposures in the liver of rabbits have been investigated. The experimental results were as follows: The metabolic pattern of pyruvate and the pyruvate metabolic responses to the 1st cold exposure (cold exposure on the 1st day) were altered by lesions of periventricular arcuate nucleus (ARC), ventromedial hypothalamus (VMH), stria terminalis (ST) and dorsal fornix (FX). The pyruvate metabolic responses to cold exposure were completely abolished by seven times repetition of daily cold exposures in rabbits with lesions of ARC, VMH and FX, as well as in each sham-operated group. In rabbits with ST lesions, the pyruvate metabolic responses to cold exposure remained even after the seven times repetition of daily cold exposures. From these results, it might be suggested that the ARC, VMH, amygdala (AMYG)-ST system and dorsal hippocampus (HPC)-FX system played a certain role in the metabolic regulation of pyruvate and in the mechanisms of pyruvate metabolic responses to the 1st cold exposure, but that only the AMYG-ST system participated in the process of pyruvate metabolic adaptation to daily repeated cold exposures.

Animals↗
PubMed2002

13C NMR isotopomer analysis reveals a connection between pyruvate cycling and glucose-stimulated insulin secretion (GSIS).

Cellular metabolism of glucose is required for stimulation of insulin secretion from pancreatic beta cells, but the precise metabolic coupling factors involved in this process are not known. In an effort to better understand mechanisms of fuel-mediated insulin secretion, we have adapted 13C NMR and isotopomer methods to measure influx of metabolic fuels into the tricarboxylic acid (TCA) cycle in insulinoma cells. Mitochondrial metabolism of [U-13C3]pyruvate, derived from [U-13C6]glucose, was compared in four clonal rat insulinoma cell 1-derived cell lines with varying degrees of glucose responsiveness. A 13C isotopomer analysis of glutamate isolated from these cells showed that the fraction of acetyl-CoA derived from [U-13C6]glucose was the same in all four cell lines (44 +/- 5%, 70 +/- 3%, and 84 +/- 4% with 3, 6, or 12 mM glucose, respectively). The 13C NMR spectra also demonstrated the existence of two compartmental pools of pyruvate, one that exchanges with TCA cycle intermediates and a second pool derived from [U-13C6]glucose that feeds acetyl-CoA into the TCA cycle. The 13C NMR spectra were consistent with a metabolic model where the two pyruvate pools do not randomly mix. Flux between the mitochondrial intermediates and the first pool of pyruvate (pyruvate cycling) varied in proportion to glucose responsiveness in the four cell lines. Furthermore, stimulation of pyruvate cycling with dimethylmalate or its inhibition with phenylacetic acid led to proportional changes in insulin secretion. These findings indicate that exchange of pyruvate with TCA cycle intermediates, rather than oxidation of pyruvate via acetyl-CoA, correlates with glucose-stimulated insulin secretion.

Animals↗
PubMed1994

Role of pyruvate in ischaemia-like conditions on cultured neurons.

In vitro, it is known that neurons in serum free mediums survive in the absence of glucose if pyruvate is present. We exposed cultured neurons on poly-L-lysine coated dishes to 6 different concentrations of pyruvate ranging from 0 to 1000 microM combined with glucose-supplement and normoxia (controls), glucose-deprivation and normoxia (hypoglycaemia), glucose-supplement and hypoxia (hypoxia), and glucose deprivation and hypoxia (ischaemia-like conditions) for 4 h. In all these conditions, lowering pyruvate below 250 microM led to a significant decrease of neuronal survival. Even in controls, there was no surviving neurons exposed to 0 microM of pyruvate. Glucose deprivation alone did not essentially influence the survival rate. Regardless of glucose deprivation, hypoxia led to an additional 23%-100% decrease of neuronal survival. When neurons were cultured above the astrocyte layers, neurons were much more tolerant with exposure to 0 microM of pyruvate for 4 h as compared to neurons on poly-L-lysine. The results indicate that pyruvate rather than glucose is essential for the energy supply to cultured neurons, probably because these neurons are immature and possess yet little capability to gain energy from glycolysis. Astrocytes may protect neurons from pyruvate deprivation by providing energy to neurons. In neuron rich culture, ischaemia is much better simulated by hypoxia-pyruvate deprivation rather than hypoxia-glucose deprivation.

Animals↗
PubMed1994

Comparison of pyruvate uptake by embryos derived from conception and non-conception natural cycles.

The uptake of pyruvate by human embryos derived from natural cycles in the first 24 h following fertilization was examined. Since only one egg was obtained and therefore only one embryo transferred to the woman, it was possible to relate pyruvate consumption by a particular embryo to the outcome of that cycle (pregnancy or no pregnancy). The results showed that embryos have a wide range of pyruvate uptake values (2-53 pmol/embryo/h) but that this variation was reduced significantly to an intermediate range of values in those embryos that were able to implant (10-30 pmol/embryo/h). An association was found between embryo morphology and pyruvate consumption. Morphologically good embryos were more likely to implant if they demonstrated an intermediate pyruvate uptake. However, poor embryos did not implant even if they had a pyruvate uptake of 10-30 pmol/embryo/h. No relationship was found between the type of infertility and pyruvate consumption of individual embryos. It is suggested that the ability of an embryo to implant is multifactorial and that both morphology and pyruvate uptake may be factors.

Embryo, Mammalian↗
PubMed1994

Hemodynamic effects of intravenous pyruvate in the intact, anesthetized dog.

OBJECTIVES: There is evidence from human studies that pyruvate improves skeletal muscle endurance, and from isolated heart preparations that pyruvate is a positive inotrope. We examined the hemodynamic effects of intravenous pyruvate in an intact, anesthetized dog preparation in order to test its effects in an intact animal. Our hypothesis was that pyruvate is a positive inotrope in the intact dog. DESIGN: Prospective, randomized, controlled trial. SETTING: Animal laboratory. SUBJECTS: Ten mongrel dogs. INTERVENTIONS: Two groups of animals were anesthetized with chloralose and urethane, mechanically ventilated, and hemodynamically monitored. The experimental group (n = 6) received an infusion of calcium pyruvate and sodium pyruvate, while the control group (n = 4) received an infusion of calcium chloride and sodium chloride. MEASUREMENTS AND MAIN RESULTS: The intravenous infusion of calcium and sodium pyruvate resulted in increased cardiac output, left ventricular contractility, and mixed venous oxygen saturation values in the experimental group compared with the control group of four dogs. There were no significant detrimental effects except an increase in the mean serum calcium concentrations in both groups. CONCLUSIONS: These data suggest that intravenous pyruvate may be a useful in vivo positive inotrope.

Analysis of Variance↗
PubMed1975

The pyruvate-dehydrogenase complex from Azotobacter vinelandii.

The pyruvate dehydrogenase complex from Axotobacter vinelandii was isolated in a five-step procedure. The minimum molecular weight of the pure complex is 600,000, as based on an FAD content of 1.6 nmol-mg protein-1. The molecular weight is 1.0-1.2 X 10(6), indicating 1 mole of lipoamide dehydrogenase dimer per complex molecule. Sodium dodecylsulphate gel electrophoretical patterns show that apart from pyruvate dehydrogenase (Mr89,000) and lipoamide dehydrogenase (Mrmonomer 56,000) two active transacetylase isoenzymes are present with molecular weight on the gel 82,000 and 59,000 but probably actually lower. The pure complex has a specific activity of the pyruvate-NAD+ reductase (overall) reaction of 10 units-mg protein-1 at 25 degrees C. The partial reactions have the following specific activities in units-mg protein-1 at 25 degrees C under standard conditions: pyruvate-K3Fe(CN)6 reductase 0.14, transacetylase 3.6 and lipoamide dehydrogenase 2.9. The properties of this complex are compared with those from other sources. NADPH reduced the FAD of lipoamide dehydrogenase as well in the complex as in the free form. NADP+ cannot be used as electron acceptor. Under aerobic conditios pyruvate oxidase reaction, dependent on Mg2+ and thiamine pyrophosphate, converts pyruvate into CO2 and acetate; V is 0.2 mumol 02-min-1-mg-1, Km(pyruvate)0.3 mM. The kinetics of this reaction shows a linear 1/velocity-1/[pyruvate] plot. K3Fe(CN)6 competes with the oxidase reaction. The oxidase activity is stimulated by AMP and sulphate and is inhibited by acetyl-CoA. The partially purified enzyme contains considerable phosphotransacetylase activity. The pure complex does not contain this activity. The physiological significance of this activity is discussed.

Acetyltransferases↗
PubMed1982

Pyruvate-dependent diauxic growth of Rhodospirillum rubrum in light.

When Rhodospirillum rubrum mutant C was first exposed to radiant energy after long-term anaerobic dark growth, the cells often exhibited a diauxic growth response. This happened with pyruvate in the medium and when cultures were exposed to a less-than-growth-saturating white light intensity of about 6,460 lx. Under the growth-saturating light condition, mutant C photometabolized and growth was not affected by Na hypophosphite, an inhibitor of pyruvate fermentation. In lower intensity light, in which diauxie occurred, initial (phase I) growth occurred by fermentation of Na pyruvate and was sensitive to Na hypophosphite inhibition. Once pyruvate was depleted, phase I growth stopped, the bacteriochlorophyll content of the cells began to increase from about 3 nmol/mg of protein, and growth finally resumed phototrophically (phase II). The lag period and phase II growth were influenced by radiant energy. By changing the white light intensity from 2,150 to 753 lx between experiments, the duration of both the lag period and the generation time of cells in phase II growth increased. Diauxic growth was pyruvate dependent. It occurred with pyruvate even if malate, a photometabolizable substrate, was added to the growth medium. Moreover, the biphasic growth response was reversible. It was observed not only with R. rubrum mutant C grown cells photosynthetically, but also when other strains of R. rubrum were placed in pyruvate medium under lowered light conditions. Only R. rubrum S1 did not exhibit the typical pyruvate-dependent diauxic growth response.

Acetates↗
PubMed1997

Regulation of synthesis of pyruvate carboxylase in the photosynthetic bacterium Rhodobacter capsulatus.

The synthesis of pyruvate carboxylase (PC) was studied by using quantitative immunoblot analysis with an antibody raised against PC purified from Rhodobacter capsulatus and was found to vary 20-fold depending on the growth conditions. The PC content was high in cells grown on pyruvate or on carbon substrates metabolized via pyruvate (lactate, D-malate, glucose, or fructose) and low in cells grown on tricarboxylic acid (TCA) cycle intermediates or substrates metabolized without intermediate formation of pyruvate (acetate or glutamate). Under dark aerobic growth conditions with lactate as a carbon source, the PC content was approximately twofold higher than that found under light anaerobic growth conditions. The results of incubation experiments demonstrate that PC synthesis is induced by pyruvate and repressed by TCA cycle intermediates, with negative control dominating over positive control. The content of PC in R. capsulatus cells was also directly related to the growth rate in continuous cultures. The analysis of intracellular levels of pyruvate and TCA cycle intermediates in cells grown under different conditions demonstrated that the content of PC is directly proportional to the ratio between pyruvate and C4 dicarboxylates. These results suggest that the regulation of PC synthesis by oxygen and its direct correlation with growth rate may reflect effects on the balance of intracellular pyruvate and C4 dicarboxylates. Thus, this important enzyme is potentially regulated both allosterically and at the level of synthesis.

Aerobiosis↗
PubMed1967

Regulatory effect of pyruvate on the glucose metabolism of Clostridium thermosaccharolyticum.

Whole cells and cell-free extracts of Clostridium thermosaccharolyticum 3814 grown in media containing 0.5% glucose or 0.6% pyruvate were evaluated for their metabolic activities toward these compounds. Glucose-grown cells rapidly fermented glucose with the production of gases (CO(2) and H(2)), acids, and alcohol, but they did not ferment pyruvate well. Pyruvate-grown cells, on the other hand, readily fermented pyruvate, while fermenting glucose at a rate of one-half that of pyruvate. An analysis of the enzyme levels in the two cell culture conditions revealed that pyruvate-grown cells had lower levels of most of the glycolytic enzymes and increased levels of the hexose monophosphate pathway enzymes. Incorporation studies with the use of labeled glucose demonstrated that cells do have a control mechanism(s) whereby they can discriminate between a carbon (glucose) and an energy (pyruvate) source, selectively utilizing glucose in the synthetic pathway while obtaining energy from the phosphoroclastic degradation of pyruvate.

Aldehyde-Lyases↗
PubMed1994

Lactate-pyruvate interconversion in blood: implications for in vivo tracer studies.

We have evaluated lactate and pyruvate kinetics in whole blood or plasma by the addition of [1-13C]lactate (n = 5) or [1-13C]pyruvate (n = 5) and application of compartmental modeling to the resulting data. Pyruvate and lactate concentrations and tracer-to-tracee ratios were measured at frequent intervals for 45 min. Pyruvate and lactate tracer-to-tracee ratios equilibrated almost completely within 3-4 min in whole blood, whereas there was no isotopic exchange in plasma. The average rate of interconversion between unlabeled lactate and pyruvate was four to five times (pyruvate to lactate) and three to four times (lactate to pyruvate) the net production rate of lactate. We conclude that there is a very rapid interconversion between lactate and pyruvate in blood that has to be considered in the interpretation of in vivo tracer studies.

Adult↗
PubMed1999

The importance of pyruvate availability to PDC activation and anaplerosis in human skeletal muscle.

No studies have singularly investigated the relationship between pyruvate availability, pyruvate dehydrogenase complex (PDC) activation, and anaplerosis in skeletal muscle. This is surprising given the functional importance attributed to these processes in normal and disease states. We investigated the effects of changing pyruvate availability with dichloroacetate (DCA), epinephrine, and pyruvate infusions on PDC activation and accumulation of acetyl groups and tricarboxylic acid (TCA) cycle intermediates (TCAI) in human muscle. DCA increased resting PDC activity sixfold (P < 0.05) but decreased the muscle TCAI pool (mmol/kg dry muscle) from 1.174 +/- 0.042 to 0.747 +/- 0.055 (P < 0.05). This was probably a result of pyruvate being diverted to acetyl-CoA and acetylcarnitine after near-maximal activation of PDC by DCA. Conversely, neither epinephrine nor pyruvate activated PDC. However, both increased the TCAI pool (1.128 +/- 0.076 to 1.614 +/- 0.188, P < 0.05 and 1.098 +/- 0.059 to 1.385 +/- 0.114, P < 0.05, respectively) by providing a readily available pool of pyruvate for anaplerosis. These data support the hypothesis that TCAI pool expansion is principally a reflection of increased muscle pyruvate availability and, together with our previous work (J. A. Timmons, S. M. Poucher, D. Constantin-Teodosiu, V. Worrall, I. A. Macdonald, and P. L. Greenhaff. J. Clin. Invest. 97: 879-883, 1996), indicate that TCA cycle expansion may be of little functional significance to TCA cycle flux. It would appear therefore that the primary effect of DCA on oxidative ATP provision is to provide a readily available pool of acetyl groups to the TCA cycle at the onset of exercise rather than increasing TCA cycle flux by expanding the TCAI pool.

Adult↗