Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Pyruvate Synthase”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7Linked to original sources
PubMed1986

Muscle enzyme activity and insulin sensitivity in type 1 (insulin-dependent) diabetes mellitus.

The mechanisms of insulin insensitivity in diabetes are poorly understood. We have therefore assessed the relationship between glucose disposal during a euglycaemic clamp, muscle glycogen formation, and the activities of insulin regulated enzymes within skeletal muscle in five Type 1 (insulin-dependent) diabetic patients, both on conventional injection therapy (HbA1 11.0 +/- 1.0 (SD) %) and after 6 weeks continuous subcutaneous insulin infusion (HbA1 7.6 +/- 1.4%, p less than 0.01). On both regimens, overnight euglycaemia before the clamp was maintained with an intravenous insulin infusion. The increase in clamp glucose requirements (insulin 0.1 U X kg-1 X h-1) between injection therapy and continuous subcutaneous insulin infusion was significant (6.2 +/- 0.9 (SE) to 7.0 +/- 0.9 mg X kg-1 X min-1, p less than 0.05), but small compared to differences between subjects. Glucose requirement remained lower than in control subjects (10.4 +/- 0.7 mg X kg-1 X min-1, p less than 0.05). The increase in muscle glycogen with the clamp was slightly higher on continuous subcutaneous insulin infusion (9.5 +/- 2.5 mg/g protein) than on injection therapy (8.5 +/- 2.4 mg/g, p less than 0.05), but less than in control subjects (17.9 +/- 2.1 mg/g, p less than 0.05). The expressed activity of glycogen synthase and pyruvate dehydrogenase increased significantly between fasting and the end of the clamps in the patients (p less than 0.001 and less than 0.005), but was not significantly different between the two treatment regimens. Expressed glycogen synthase activity at the end of the clamp was lower on both treatments than in control subjects (p less than 0.05). Both enzyme activities were, however, highly correlated with glucose requirement between patients, (r = 0.89-0.94, p less than 0.05-0.02), and glycogen synthase was similarly correlated in the control subjects (r = 0.84, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1979

Pyruvate dehydrogenase, lipoamide dehydrogenase and citrate synthase activity in fibroblasts from patients with Friedreich's and Charlevoix-Saguenay ataxia.

The activity of lipoamide dehydrogenase and two closely related enzymes was studied simultaneously in early, mild, and late passage fibroblast cultures. Friedreich's ataxia fibroblasts tended to lose pyruvate dehydrogenase and citrate synthase activities, while lipoamide dehydrogenase activity remained constant with aging of the cells. Mean pyruvate dehydrogenase activity was lower over-all in fibroblasts from ataxics. Mean citrate synthase activity was higher in ataxic fibroblasts. Present tissue culture media do not represent the best conditions in which to reproduce cofactor binding defects such as those found in other genetic diseases with structural enzyme mutations.

Ataxia↗
PubMed2000

Crystal structure of Escherichia coli malate synthase G complexed with magnesium and glyoxylate at 2.0 A resolution: mechanistic implications.

The crystal structure of selenomethionine-substituted malate synthase G, an 81 kDa monomeric enzyme from Escherichia coli has been determined by MAD phasing, model building, and crystallographic refinement to a resolution of 2.0 A. The crystallographic R factor is 0.177 for 49 242 reflections observed at the incident wavelength of 1.008 A, and the model stereochemistry is satisfactory. The basic fold of the enzyme is that of a beta8/alpha8 (TIM) barrel. The barrel is centrally located, with an N-terminal alpha-helical domain flanking one side. An inserted beta-sheet domain folds against the opposite side of the barrel, and an alpha-helical C-terminal domain forms a plug which caps the active site. Malate synthase catalyzes the condensation of glyoxylate and acetyl-coenzyme A and hydrolysis of the intermediate to yield malate and coenzyme A, requiring Mg(2+). The structure reveals an enzyme-substrate complex with glyoxylate and Mg(2+) which coordinates the aldehyde and carboxylate functions of the substrate. Two strictly conserved residues, Asp631 and Arg338, are proposed to provide concerted acid-base chemistry for the generation of the enol(ate) intermediate of acetyl-coenzyme A, while main-chain hydrogen bonds and bound Mg(2+) polarize glyoxylate in preparation for nucleophilic attack. The catalytic strategy of malate synthase appears to be essentially the same as that of citrate synthase, with the electrophile activated for nucleophilic attack by nearby positive charges and hydrogen bonds, while concerted acid-base catalysis accomplishes the abstraction of a proton from the methyl group of acetyl-coenzyme A. An active site aspartate is, however, the only common feature of these two enzymes, and the active sites of these enzymes are produced by quite different protein folds. Interesting similarities in the overall folds and modes of substrate recognition are discussed in comparisons of malate synthase with pyruvate kinase and pyruvate phosphate dikinase.

Amino Acid Sequence↗
PubMed1990

Fasting hyperglycemia normalizes oxidative and nonoxidative pathways of insulin-stimulated glucose metabolism in noninsulin-dependent diabetes mellitus.

The present studies were undertaken to determine whether fasting hyperglycemia can compensate for decreased insulin-stimulated glucose disposal, oxidation, and storage in noninsulin-dependent diabetes mellitus (NIDDM) as well as to determine whether hyperglycemia normalizes insulin-stimulated skeletal muscle glycogen synthase and pyruvate dehydrogenase (PDH) activities. To accomplish this, we used the glucose clamp technique with isotopic determination of glucose disposal and indirect calorimetry for measuring the pathways of glucose metabolism, and vastus lateralis muscle biopsies to determine the effects of insulin on glycogen synthase and PDH activities. Nine patients with NIDDM and eight matched non-diabetic subjects were infused with insulin (40 mU/m2.min) while plasma glucose was maintained at the prevailing fasting concentration. During insulin infusion, rates of glucose disposal, storage, and oxidation were the same in the two groups. Insulin infusion significantly activated glycogen synthase fractional velocity to the same extent in NIDDM (0.210 +/- 0.056 vs. 0.332 +/- 0.079) and controls (0.192 +/- 0.036 vs. 0.294 +/- 0.050). Insulin infusion increased PDH fractional velocity in controls (from 0.281 +/- 0.022 to 0.404 +/- 0.038), but not in NIDDM (from 0.356 +/- 0.043 to 0.436 +/- 0.060), although the activity of PDH during insulin infusion did not differ between the groups. We conclude that prevailing fasting hyperglycemia normalizes the nonoxidative and oxidative pathways of insulin-stimulated glucose in metabolism in NIDDM and may act as a homeostatic mechanism to normalize muscle glucose metabolism.

Diabetes Mellitus, Type 2↗
PubMed1998

High-temperature perturbation of starch synthesis is attributable to inhibition of ADP-glucose pyrophosphorylase by decreased levels of glycerate-3-phosphate in growing potato tubers

To investigate the short-term effect of elevated temperatures on carbon metabolism in growing potato (Solanum tuberosum L.) tubers, developing tubers were exposed to a range of temperatures between 19 degreesC and 37 degreesC. Incorporation of [14C]glucose (Glc) into starch showed a temperature optimum at 25 degreesC. Increasing the temperature from 23 degreesC or 25 degreesC up to 37 degreesC led to decreased labeling of starch, increased labeling of sucrose (Suc) and intermediates of the respiratory pathway, and increased respiration rates. At elevated temperatures, hexose-phosphate levels were increased, whereas the levels of glycerate-3-phosphate (3PGA) and phosphoenolpyruvate were decreased. There was an increase in pyruvate and malate, and a decrease in isocitrate. The amount of adenine diphosphoglucose (ADPGlc) decreased when tubers were exposed to elevated temperatures. There was a strong correlation between the in vivo levels of 3PGA and ADPGlc in tubers incubated at different temperatures, and the decrease in ADPGlc correlated very well with the decrease in the labeling of starch. In tubers incubated at temperatures above 30 degreesC, the overall activities of Suc synthase and ADPGlc pyrophosphorylase declined slightly, whereas soluble starch synthase and pyruvate kinase remained unchanged. Elevated temperatures led to an activation of Suc phosphate synthase involving a change in its kinetic properties. There was a strong correlation between Suc phosphate synthase activation and the in vivo level of Glc-6-phosphate. It is proposed that elevated temperatures lead to increased rates of respiration, and the resulting decline of 3PGA then inhibits ADPGlc pyrophosphorylase and starch synthesis.

Journal Article↗
PubMed1976

Regulation of malate oxidation in isolated mung bean mitochondria: I. Effects of oxaloacetate, pyruvate, and thiamine pyrophosphate.

In order to investigate the relationship between malate oxidation and subsequent cycle reactions, the effects of oxaloacetate, pyruvate, and thiamine pyrophosphate on malate oxidation in mung bean (Phaseolus aureus var. Jumbo) hypocotyl mitochondria were quantitatively examined. Malate oxidation was optimally stimulated by addition of pyruvate and thiamine pyrophosphate, whose addition lowered the apparent Km for malate from 5 mm to 0.1 mm. Intermediate analysis showed that the stimulatory effect was correlated with removal of oxaloacetate to citrate. Oxaloacetate added alone was shown not to be metabolized until addition of pyruvate and thiamine pyrophosphate; then oxaloacetate was converted in part to pyruvate and also to citrate. These results establish that malate oxidation in mung bean mitochondria is subject to control by oxaloacetate levels, which are primarily determined by the resultant of the activities of malate dehydrogenase, citrate synthase, and pyruvate dehydrogenase.

Journal Article↗
PubMed1995

Glucagon stimulates phosphorylation of different peptides in isolated periportal and perivenous hepatocytes.

The perivenous and periportal zones of the liver acinus differ in enzyme complements and capacities for gluconeogenesis, glycolysis and other metabolic processes. The biochemical factors governing this metabolic zonation are still poorly understood. Glucagon-mediated protein phosphorylation is an important factor in the regulation of hepatic metabolism. Here we show, by comparing the 32P-labelling pattern of isolated periportal and perivenous hepatocytes, that glucagon promotes the phosphorylation of zone-specific peptides as well as three common peptides (glycogen phosphorylase, glycogen synthase and pyruvate kinase) in the two cell types. We propose that the zone-specific phosphorylation of peptides is an important factor governing the shortterm zonation of metabolic processes in the liver.

Animals↗
PubMed1988

Decreased insulin sensitivity and muscle enzyme activity in elderly subjects.

Skeletal muscle glycogen deposition, and the activation of muscle glycogen synthase and pyruvate dehydrogenase during a hyerinsulinaemic euglycaemic clamp have been measured in six young and six elderly males matched for body mass index, physical activity and diet. Clamp glucose requirement (insulin, 0.1 U kg-1 h-1) was significantly lower in the older subjects (8.0 +/- 0.4 mg kg-1 min-1) than in younger subjects (10.5 +/- 0.6 mg kg-1 min-1, P less than 0.02). Although the older subjects had a 6.5% decrease in lean body mass, clamp glucose requirement expressed per unit of lean body mass was also significantly decreased in the older subjects (10.2 +/- 0.5 vs. 12.4 +/- 0.6 mg kg-1 min-1, P less than 0.05). The increase in muscle glycogen with the clamp was decreased by 33% in the older subjects (elderly: 13.1 +/- 1.3 mg g-1 protein, young: 19.6 +/- 2.2 mg g-1 protein; P less than 0.05), and was strongly correlated with clamp glucose requirement (r = 0.72, P less than 0.01). Glucose-6-phosphate independent glycogen synthase activity increased significantly between fasting and the end of the clamps in both groups (P less than 0.001), but was lower at the end of the clamp in the older subjects (P less than 0.05). Glycogen synthase activity at the end of the clamp correlated with both clamp glucose requirement (r = 0.83, P less than 0.01) and muscle glycogen deposition (r = 0.73, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2006

ChREBP binding to fatty acid synthase and L-type pyruvate kinase genes is stimulated by glucose in pancreatic beta-cells.

Pancreatic beta-cell dysfunction is central to the pathogenesis of type 2 diabetes and may involve secretory failure through glucolipotoxity. The relative importance of the transcription factors carbohydrate-responsive element binding protein (ChREBP), sterol-responsive element binding protein-1c (SREBP-1c), and upstream stimulatory factor (USF) in the induction of lipogenic genes by glucose remains unclear. By confocal imaging, we show that ChREBP translocates to the nucleus in MIN6 beta cells in response to glucose. Both ChREBP and SREBP-1c were required for the induction of the fatty acid synthase (FAS) promoter by glucose, and chromatin immunoprecipitation (ChIP) assay revealed that glucose induced the binding of both ChREBP and SREBP-1c to the FAS promoter without affecting USF2 binding. By contrast, ChIP assay revealed that high glucose prompted direct binding of ChREBP, but not SREBP-1c or USF2, to the liver-type pyruvate kinase (L-PK) promoter. This event was indispensable for the induction of the L-PK gene by glucose, as demonstrated by RNA silencing, single-cell promoter analysis, and quantitative real-time PCR. We conclude that ChREBP is a critical regulator of lipogenic genes in the beta cell and may play a role in the development of glucolipotoxicity and beta cell failure through alteration of gene expression in type 2 diabetes.

Active Transport, Cell Nucleus↗
PubMed2004

Electron transfer in acetohydroxy acid synthase as a side reaction of catalysis. Implications for the reactivity and partitioning of the carbanion/enamine form of (alpha-hydroxyethyl)thiamin diphosphate in a "nonredox" flavoenzyme.

Acetohydroxy acid synthases (AHAS) are thiamin diphosphate- (ThDP-) and FAD-dependent enzymes that catalyze the first common step of branched-chain amino acid biosynthesis in plants, bacteria, and fungi. Although the flavin cofactor is not chemically involved in the physiological reaction of AHAS, it has been shown to be essential for the structural integrity and activity of the enzyme. Here, we report that the enzyme-bound FAD in AHAS is reduced in the course of catalysis in a side reaction. The reduction of the enzyme-bound flavin during turnover of different substrates under aerobic and anaerobic conditions was characterized by stopped-flow kinetics using the intrinsic FAD absorbance. Reduction of enzyme-bound FAD proceeds with a net rate constant of k' = 0.2 s(-1) in the presence of oxygen and approximately 1 s(-1) under anaerobic conditions. No transient flavin radicals are detectable during the reduction process while time-resolved absorbance spectra are recorded. Reconstitution of the binary enzyme-FAD complex with the chemically synthesized intermediate 2-(hydroxyethyl)-ThDP also results in a reduction of the flavin. These data provide evidence for the first time that the key catalytic intermediate 2-(hydroxyethyl)-ThDP in the carbanionic/enamine form is not only subject to covalent addition of 2-keto acids and an oxygenase side reaction but also transfers electrons to the adjacent FAD in an intramolecular redox reaction yielding 2-acetyl-ThDP and reduced FAD. The detection of the electron transfer supports the idea of a common ancestor of acetohydroxy acid synthase and pyruvate oxidase, a homologous ThDP- and FAD-dependent enzyme that, in contrast to AHASs, catalyzes a reaction that relies on intercofactor electron transfer.

Acetolactate Synthase↗
PubMed2002

Analysis of gluconeogenic and anaplerotic enzymes in Campylobacter jejuni: an essential role for phosphoenolpyruvate carboxykinase.

Campylobacter jejuni is unable to utilize glucose as a carbon source due to the absence of the key glycolytic enzyme 6-phosphofructokinase. The genome sequence of C. jejuni NCTC 11168 indicates that homologues of all the appropriate enzymes for gluconeogenesis from phosphoenolpyruvate (PEP) are present, in addition to the anaplerotic enzymes pyruvate carboxylase (PYC), phosphoenolpyruvate carboxykinase (PCK) and malic enzyme (MEZ). Surprisingly, a pyruvate kinase (PYK) homologue is also present. To ascertain the role of these enzymes, insertion mutants in pycA, pycB, pyk and mez were generated. However, this could not be achieved for pckA, indicating that PCK is an essential enzyme in C. jejuni. The lack of PEP synthase and pyruvate orthophosphate dikinase activities confirmed a unique role for PCK in PEP synthesis. The pycA mutant was unable to grow in defined medium with pyruvate or lactate as the major carbon source, thus indicating an important role for PYC in anaplerosis. Sequence and biochemical data indicate that the PYC of C. jejuni is a member of the alpha4beta4, acetyl-CoA-independent class of PYCs, with a 65.8 kDa subunit containing the biotin moiety. Whereas growth of the mez mutant was comparable to that of the wild-type, the pyk mutant displayed a decreased growth rate in complex medium. Nevertheless, the mez and pyk mutants were able to grow with pyruvate, lactate or malate as carbon sources in defined medium. PYK was present in cell extracts at a much higher specific activity [>800 nmol x min(-1) x (mg protein)(-1)] than PYC or PCK [<65 nmol x min(-1) x (mg protein)(-1)], was activated by fructose 1,6-bisphosphate and displayed other regulatory properties strongly indicative of a catabolic role. It is concluded that PYK may function in the catabolism of unidentified substrates which are metabolized through PEP. In view of the high K(m) of MEZ for malate (approximately 9 mM) and the lack of a growth phenotype of the mez mutant, MEZ seems to have only a minor anaplerotic role in C. jejuni.

Bacterial Proteins↗
PubMed1985

The protein phosphatases involved in cellular regulation. 1. Modulation of protein phosphatases-1 and 2A by histone H1, protamine, polylysine and heparin.

The phosphorylase phosphatases in rat and rabbit liver cytosol that are markedly stimulated by histone H1, protamine and polylysine were identified as protein phosphatases-2A0, 2A1 and 2A2 by anion-exchange chromatography, gel-filtration and immunotitration experiments. Histone H1 and protamine also stimulated the dephosphorylation of phosphorylase kinase, glycogen synthase, fructose-1,6-bisphosphatase, pyruvate kinase, acetyl-CoA carboxylase and phenylalanine hydroxylase by phosphatases-2A1 and 2A2, and with several of these substrates activation was even more striking (20-100-fold) than that observed with phosphorylase (approximately 5-fold). Activation by basic polypeptides did not involve dissociation of these phosphatases to the free catalytic subunit. The dephosphorylation of phosphorylase by protein phosphatase-1 was suppressed by basic polypeptides, protamine and polylysine being the most potent inhibitors. However, the dephosphorylation of glycogen synthase, pyruvate kinase and acetyl-CoA carboxylase were markedly stimulated by histone H1 and protamine (2-13-fold). Consequently, with the appropriate substrates, protein phosphatase-1 can also be regarded as a basic-polypeptide-activated protein phosphatase. Heparin stimulated (1.5-2-fold) the dephosphorylation of phosphorylase by phosphatases-2A0 and 2A1, provided that Mn2+ was present, but phosphatase-2A2 and the free catalytic subunit of phosphatase-2A were unaffected. Heparin, in conjunction with Mn2+, also stimulated (1.5-fold) the dephosphorylation of glycogen synthase (labelled in sites 3 abc), phosphorylase kinase and phenylalanine hydroxylase by phosphatase-2A1, but not by phosphatase-2A2. By contrast, the dephosphorylation of phosphorylase and phosphorylase kinase by protein phosphatase-1 was inhibited by heparin. However, dephosphorylation of glycogen synthase and pyruvate kinase by phosphatase-1 was stimulated by this mucopolysaccharide. The studies demonstrate that basic proteins can be used to distinguish protein phosphatase-1 from protein phosphatase-2A, but only if phosphorylase is employed as substrate. Optimal differentiation of the two phosphatases is observed at 30 micrograms/ml protamine or at heparin concentrations greater than 150 microM.

Animals↗
PubMed1992

Glutamate-malate metabolism in liver mitochondria. A model constructed on the basis of mitochondrial levels of enzymes, specificity, dissociation constants, and stoichiometry of hetero-enzyme complexes.

The level of aspartate aminotransferase in liver mitochondria was found to be approximately 140 microM, or 2-3 orders of magnitude higher than its dissociation constant in complexes with the inner mitochondrial membrane and the high molecular weight enzymes (M(r) = 1.6 x 10(5) to 2.7 x 10(6)) carbamyl-phosphate synthase I, glutamate dehydrogenase, and the alpha-ketoglutarate dehydrogenase complex. The total concentration of aminotransferase-binding sites on these structures in liver mitochondria was more than sufficient to accommodate all of the aminotransferase. Therefore, in liver mitochondria, the aminotransferase could be associated with the inner mitochondrial membrane and/or these high molecular weight enzymes. The aminotransferase in these hetero-enzyme complexes could be supplied with oxalacetate because binding of aminotransferase to the high molecular weight enzymes can enhance binding of malate dehydrogenase, and binding of both malate dehydrogenase and the aminotransferase facilitated binding of fumarase. The level of malate dehydrogenase was found to be so high (140 microM) in liver mitochondria, compared with that of citrate synthase (25 microM) and the pyruvate dehydrogenase complex (0.3 microM), that there would also be a sufficient supply of oxalacetate to citrate synthase-pyruvate dehydrogenase.

Animals↗
PubMed1976

Heme synthesis in hereditary hemolytic anemias: decreased delta-aminolevulinic acid synthetase in hemoglobin Köln disease.

The activities of delta-aminolevulinic acid (ALA) synthetase and ALA dehydratase in cord blood erythrocytes of newborn infants and peripheral blood red cells of patients with beta-thalassemia major, beta-thalassemia intermedia, hemoglobin Köln (Hb Köln) disease, sickle cell anemia, and pyruvate kinase deficiency were studied. The activity of ALA dehydratase did not vary appreciably with the number of immature RBC (reticulocytes and nucleated red blood cells) or the severity of the hemolytic anemia except in pyruvate kinase deficiency. The activity of ALA synthetase was linearly correlated with the number of immature RBC (r=0.974, p is less than 0.001). The ALA synthetase activity was significantly decreased in the RBC of Hb Köln (p is less than 0.01) when compared with the activity in immature RBC of newborns and of patients with pyruvate kinase deficiency, sickle cell anemia, and thalassemia intermedia.

5-Aminolevulinate Synthetase↗
PubMed1987

Covalently bound pyruvate in phosphopantothenoylcysteine decarboxylase from horse liver.

Horse liver phosphopantothenoylcysteine decarboxylase (EC 4.1.1.36) incorporates nonexchangeable tritium from borotritide with a decrease of the activity. Substrate prevents both tritium incorporation and the decrease in activity. Acid and base hydrolysis of the tritiated protein releases labeled lactate identified by high-voltage paper electrophoresis, paper chromatography and silicic acid chromatography. These results indicate the presence of pyruvate covalently bound through an ester linkage to phosphopantothenoylcysteine decarboxylase which is then another example of a mammalian enzyme in which pyruvate is involved in a catalytic activity.

Amino Acid Transport Systems, Neutral↗
PubMed1991

Effects of amphotericin B on the glucose metabolism in Saccharomyces cerevisiae cells. Studies by 13C-, 1H-NMR and biochemical methods.

A new approach is proposed to investigate the metabolic perturbation induced by drugs in cells. The effects of various concentrations of amphotericin B on the aerobic [1-13C]glucose metabolism in glucose-grown repressed Saccharomyces cerevisiae cells were studied as a function of time using 13C-, 1H-NMR and biochemical methods. The 13C enrichment of different compounds such as ethanol, glycerol and trehalose were determined by 1H-NMR spectroscopy. In the absence of amphotericin B, glycerol diffuses slowly from the internal to the external medium, whereas in its presence this diffusion is greatly facilitated by the formation of pores in the cell membrane. Amphotericin B has been found to exert a marked influence on the glucose consumption and the production of all metabolites; for example, at 1 microM, the glucose consumption and the production of ethanol decrease while the production of glycerol and trehalose increases. The 13C relative enrichments of ethanol, glycerol and trehalose are almost the same with and without the drug. Thus it can be concluded that amphotericin B induces a large effect on the production of these compounds in the cytosol but shows no significant influence on the mechanism of their formation. Upon addition of glucose, all the amino acid concentrations decrease continuously with time; this effect is more pronounced in the presence of the drug. The ratio of the integrated resonances of glutamate (C2 + C3)/C4 reflects the activity of pyruvate carboxylase relative to citrate synthase rather than to pyruvate dehydrogenase. Without amphotericin B, this ratio (approximately 1.0) is practically constant upon addition of glucose which suggests that the activities of pyruvate carboxylase and citrate synthase are equivalent. By contrast, upon coaddition of 25 mM glucose and 1 microM amphotericin B, the glutamate C4 resonance remains virtually unchanged while that of glutamate C2 is much smaller than in its absence and continuously decreases with time. It seems likely that amphotericin B induces a reduction in the activity of pyruvate carboxylase in the mitochondria.

Alanine↗
PubMed1993

Contribution of muscle and liver to glucose-fatty acid cycle in humans.

To examine the influence of elevated free fatty acid (FFA) levels on hepatic glucose production (HGP) and oxidative and nonoxidative pathways of glucose metabolism, 12 healthy subjects participated in two euglycemic insulin-clamp studies performed with and without infusion of Intralipid plus heparin. To elucidate the role of skeletal muscle in this putative interaction, we performed muscle biopsies for the measurement of activities of glycogen synthase (GS), pyruvate dehydrogenase (PDH), and carnitine palmitoyltransferase (CPT). Infusion of Intralipid plus heparin caused an increase in plasma FFA concentrations and rate of lipid oxidation (measured by indirect calorimetry) that was not inhibited by insulin. Suppression of HGP by insulin was impaired by elevated plasma FFA levels. Furthermore, the increase in plasma FFA was associated with a 20% reduction in total glucose metabolism (P < 0.01), which was completely accounted for by a reduction in the rate of glucose oxidation. Although the fractional activity of GS was increased by insulin, elevation of plasma FFA had no influence on this key enzyme of glycogen synthesis. In addition, the activities of PDH and CPT were uninfluenced by the elevation of FFA, suggesting that oxidative processes in skeletal muscle were not a major target for the operative glucose-fatty acid cycle under the current conditions. Taken together, the data indicate that the interaction between FFA and glucose metabolism also involves impaired suppression of HGP by insulin.

Adult↗
PubMed2003

The early ontogeny of digestive and metabolic enzyme activities in two commercial strains of arctic charr (Salvelinus alpinus L.).

The extent to which growth performance is linked to digestive or energetic capacities in the early life stages of a salmonid species was investigated. We compared two strains of Arctic charr known to have different growth potentials during their early development (Fraser and Yukon gold). Trypsin, lipase, and amylase activities of whole alevins were measured at regular intervals from hatching through 65 days of development. To assess catabolic ability, we also measured five enzymes representing the following metabolic pathways: amino acid oxidation (amino aspartate transferase), fatty acid oxidation (beta-hydroxy acyl CoA-dehydrogenase), tricarboxylic acid cycle (citrate synthase), glycolysis (pyruvate kinase), and anaerobic glycolysis (lactate dehydrogenase). The measurement of these enzyme activities in individual fish allowed a clear evaluation of digestive capacity in relation to energetic demand. We also compared triploid and diploid individuals within the Yukon gold strain. For the whole experimental period, diploid Yukon gold fish exhibited the highest growth rate (1.08+/-0.18% length/day) followed by triploid Yukon gold fish (1.00+/-0.28% length/day) and finally Fraser strain fish (0.84+/-0.28% length/day). When differences in enzyme activities were observed, the Fraser strain showed higher enzyme activities at a given length than the Yukon gold strain (diploid and triploid). Higher growth performance appears to be linked to lower metabolic capacity. Our results suggest that fish may have to reach an important increase in the ratio of digestive to catabolic enzyme activities or a leveling off of metabolic enzyme activities before the onset of large increases in mass.

3-Hydroxyacyl CoA Dehydrogenases↗