Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:6.4.1.1 (pyruvate carboxylase)
1,516 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Fatty livers and kidney syndrome (FLKS) was induced in young broiler chickens by giving them a diet composed principally of wheat and meat meal. 2. FLKS resulted in reduced growth and increased liver weight; fasting for 18 h increased mortality, liver lipid and the specific activity of hepatic ATP-citrate lyase compared with birds fed on a commercial diet. The specific activities of hepatic fructose-1,6-diphosphate-1-phosphohydrolase and pyruvate carboxylase were reduced in birds suffering from FLKS and fasted for 18 h. 3. Feeding of the FLKS-inducing diet supplemented with 150 g animal tallow/kg for 54 h considerably reduced mortality while restoring liver composition and enzyme activities towards those observed in birds fed a commercial diet. Investigations indicated that the glycerol component of the fat was not responsible for the observed responses. 4. The present results suggest that in FLKS insufficiencies of biotin are induced in specific enzyme systems, but the syndrome may be alleviated without the use of supplementary biotin. 5. The evidence indicates that, when stressed, birds affected by FLKS diet from the hypoglycaemia occurring as a result of a reduced capacity for gluconeogenesis.
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PMID:A biochemical explanation for the fatty liver and kidney syndrome of broilers: its alleviation by the short-term use of dietary fat. 20 Dec 68

1. Measurements have been made of the activities of enzymes of the glycolytic route, the pentose phosphate pathway, the tricarboxylic acid cycle and lipogenesis in liver and adipose tissue from genetically obese (fa/fa) rats and their lean litter mates (fa/ --). The effect of food restriction for a period of three weeks on the enzyme profile of liver and adipose tissue of the obese rat was also studied. 2. The most striking increases in enzyme activity in livers from obese rats were: (a) among enzymes of lipogenesis; ATP-citrate lyase, acetyl-CoA carboxylase, fatty acid synthetase, malate dehydrogenase (decarboxylating) and cytoplasmic glycerolphosphate dehydrogenase; (b) within the pentose phosphate pathway; glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase; (c) within the glycolytic pathway; glucokinase, pyruvate kinase and lactate dehydrogenase. All of these enzymes showed a significant increase in activity on the basis of U/g liver and U/mg DNA. In adipose tissue all the enzymes of lipogenesis, of the glycolytic route, of the oxidative segment of the pentose phosphate pathway and of the tricarboxylic acid cycle were increased when expressed as U/2 fat pads or as U/mg DNA. 3. The restriction of the food intake of obese rats to that consumed by their lean litter mates for periods of three weeks did not produce the expected adaptive decrease in enzymes of lipogenesis; in adipose tissue, only ATP-citrate lyase and malate dehydrogenase (decarboxylating) showed a marked decrease; no significant change was found in adipose tissue or liver of the activities of acetyl-CoA carboxylase and fatty acid synthetase, when expressed on a cell basis (U/mg DNA). The non-oxidative enzymes of the pentose phosphate pathway and enzymes involved in glycerogenesis (pyruvate carboxylase, malate dehydrogenase and phosphoenolpyruvate carboxykinase) all increased in adipose tissue from limit-fed obese rats. 4. The rate of conversion of specifically labelled glucose to (14C)O2 and 14C-labelled lipid by pieces of adipose tissue and by liver slices was also measured. Insulin caused an increase in the conversion of (1-14C)glucose to (14C)O2 and 14C-labelled lipid in obese rats fed ad libitum, limit-fed rats and in their lean litter mates. 5. The results are discussed in relation to the raised insulin and hypothyroid state of the obese rat. The effect of this altered hormonal status on the activity of cyclic nucleotide phosphodiesterases and cellular levels of adenosine 3' :5'-monophosphate and guanosine 3' :5'-monophosphate and guanosine 3' :5'-monophosphate in relation to the obese syndrome is considered.
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PMID:Adaptive responses of enzymes of carbohydrate and lipid metabolism to dietary alteration in genetically obese Zucker rats (fa/fa). 71 Mar 95

The effect of age and nutritional status on the synthesis of fatty acids from a variety of labeled substrates by human adipose tissue in vitro was investigated. The results of this study clearly demonstrate that, although human adipose tissue is able to oxidize glucose to CO2, its ability to incorporate glucose-carbon into long chain fatty acids is negligible. Although the utilization of acetate for the synthesis of fatty acids by adipose tissue is substantial in the presence of glucose and insulin, its physiologic significance in human under normal dietary conditions is questionable. That the capacity of human adipose tissue is limited is further supported by (1) a negligible incorporation of pyruvate-3-14C (up to 25 mM concentration in the incubation medium) into fatty acids, (2) a lack of stimulation in lipogenesis by human adipose tissue after refeeding a diet high in carbohydrate and very low in fat to a previously starved human, and (3) an extremely low activity of pyruvate carboxylase and ATP-citrate lyase in adipose tissues from humans of varying ages. The activities of other key lipogenic enzymes, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and NADP-malate dehydrogenase, are also low. These enzymes can be stimulated in human adipose tissue after a fasting-refeeding regimen. The activity of phosphoenolpyruvate carboxykinase is also very low in human adipose tissue,and it is suggested that a pathway of glyceroneogenesis may not play a significant role in human adipose tissue. In light of our results, together with previous reports, it is possible to conclude that the capacity of human adipose tissue to utilize a dietary carbohydrate for the synthesis of fatty acids is extremely low and that the liver plays a major role in the biosynthesis of endogenous fatty acids from dietary carbohydrate in the human.
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PMID:Fatty acid synthesis by human adipose tissue. 111 80

The rate of utilization of pyruvate (at various concentrations) was measured in lymphocytes prepared from rat mesenteric lymph nodes. The quantitative contribution of pyruvate to CO2, lactate, aspartate, alanine, citrate, acetate, acetyl-CoA and ketone bodies accounted for the pyruvate metabolized. Pyruvate utilization was depressed by increasing concentrations of pyruvate. The maximum catalytic activities and selected intracellular distributions of the following enzymes of pyruvate, citrate and acetyl-CoA metabolism were measured: citrate synthase, ATP-citrate lyase, lactate dehydrogenase, acetyl-CoA hydrolase, acetylcarnitine transferase, NAD+- and NADP+- isocitrate dehydrogenases, HMG-CoA lyase, HMG-CoA synthase, Pyruvate dehydrogenase, acetoacetyl-CoA thiolase, 3-oxoacid-CoA transferase, 3-hydroxybutyrate dehydrogenase and pyruvate carboxylase. Acetyl-CoA formed from pyruvate did not contribute to the respiratory energy metabolism of resting lymphocytes. Instead acetyl-CoA was converted to acetoacetate by reactions which may favour the pathway catalyzed by acetoacetyl-CoA thiolase and 3-oxoacid-CoA transferase. Acetate, acetyl- and palmitoyl-carnitine inhibited the decarboxylation of [1-14C] pyruvate. These observations may be connected with the suppression of pyruvate utilization by increased pyruvate substrate concentration. Only very small amounts of either pyruvate or acetate were incorporated into lipids in resting lymphocytes. The amounts incorporated were partitioned in approximately the same pattern into FFA, T.G., cholesterol and cholesterol esters. Taken together the data show that pyruvate metabolism is directed inter alia at the formation of acetoacetate which may serve as a lipid synthesis precursor. When pyruvate utilization and metabolism was enhanced by concanavalin A, then acetoacetate formation was not favoured and from this it is proposed that the acetyl units may then be directed into lipid synthesis and may also make a contribution to the energy metabolism of the activated lymphocyte.
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PMID:Pyruvate metabolism by lymphocytes: evidence for an additional ketogenic tissue. 261 47

Fat-cells were prepared from rat and guinea-pig epididymal adipose tissue and compared on the basis of the intracellular distributions and activities of enzymes and with respect to their utilization of various U-(14)C-labelled substrates for lipogenesis. 1. Compared with the rat, guinea-pig extramitochondrial enzyme activities differed in that aconitate hydratase, alanine aminotransferase, ATP-citrate lyase, lactate dehydrogenase, NAD-malate dehydrogenase, NADP-malate dehydrogenase and phosphoenolpyruvate carboxykinase activities were appreciably lower, whereas aspartate aminotransferase, glucose 6-phosphate dehydrogenase, NADP-isocitrate dehydrogenase and 6-phosphogluconate dehydrogenase activities were appreciably higher. Mitochondrial activities of citrate synthase, NADP-isocitrate dehydrogenase and pyruvate carboxylase were appreciably lower, whereas mitochondrial activities of aspartate aminotransferase, glutamate dehydrogenase, NAD-malate dehydrogenase and phosphoenolpyruvate carboxykinase were higher in the guinea pig compared with the rat. 2. In general guinea-pig fat-cells incorporated acetate and lactate into fatty acids more readily than rat fat-cells, whereas rat fat-cells incorporated glucose and pyruvate more readily than guinea-pig fat-cells. 3. Acetate stimulated the incorporation of glucose into fatty acids in rat fat-cells, but had no appreciable effect upon this process in guinea-pig fat-cells. Acetate greatly decreased the incorporation of lactate into fatty acids in cells from both species. 4. Lactate/pyruvate ratios produced by incubation of guinea-pig cells with glucose+insulin were very low compared with those found with rat cells under the same conditions. 5. With glucose (+insulin) or with glucose+acetate (+insulin) as substrates guinea-pig cells produced enough NADPH by the hexose monophosphate pathway to satisfy the NADPH requirements of lipogenesis. In rat fat-cells under the same conditions, hexose monophosphate-pathway NADPH provision was not sufficient to meet the requirements of lipogenesis. 6. These results are discussed, particularly in relationship to the disposition of cytosolic reducing equivalents in the cells.
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PMID:Lipogenesis in rat and guinea-pig isolated epididymal fat-cells. 415 67

1. Superovulated rat ovary was found to contain high activities of NADP-malate dehydrogenase and NADP-isocitrate dehydrogenase. The activity of each enzyme was approximately four times that of glucose 6-phosphate dehydrogenase and equalled or exceeded the activities reported to be present in other mammalian tissues. Fractionation of a whole tissue homogenate of superovulated rat ovary indicated that both enzymes were exclusively cytoplasmic. The tissue was also found to contain pyruvate carboxylase (exclusively mitochondrial), NAD-malate dehydrogenase and aspartate aminotransferase (both mitochondrial and cytoplasmic) and ATP-citrate lyase (exclusively cytoplasmic). 2. The kinetic properties of glucose 6-phosphate dehydrogenase, NADP-malate dehydrogenase and NADP-isocitrate dehydrogenase were determined and compared with the whole-tissue concentrations of their substrates and NADPH; NADPH is a competitive inhibitor of all three enzymes. The concentrations of glucose 6-phosphate, malate and isocitrate in incubated tissue slices were raised at least tenfold by the addition of glucose to the incubation medium, from the values below to values above the respective K(m) values of the dehydrogenases. Glucose doubled the tissue concentration of NADPH. 3. Steroidogenesis from acetate is stimulated by glucose in slices of superovulated rat ovary incubated in vitro. It was found that this stimulatory effect of glucose can be mimicked by malate, isocitrate, lactate and pyruvate. 4. It is concluded that NADP-malate dehydrogenase or NADP-isocitrate dehydrogenase or both may play an important role in the formation of NADPH in the superovulated rat ovary. It is suggested that the stimulatory effect of glucose on steroidogenesis from acetate results from an increased rate of NADPH formation through one or both dehydrogenases, brought about by the increases in the concentrations of malate, isocitrate or both. Possible pathways involving the two enzymes are discussed.
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PMID:The role of nicotinamide-adenine dinucleotide phosphate-dependent malate dehydrogenase and isocitrate dehydrogenase in the supply of reduced nicotinamide-adenine dinucleotide phosphate for steroidogenesis in the superovulated rat ovary. 439 12

1. A method is described for extracting separately mitochondrial and extramitochondrial enzymes from fat-cells prepared by collagenase digestion from rat epididymal fat-pads. The following distribution of enzymes has been observed (with the total activities of the enzymes as units/mg of fat-cell DNA at 25 degrees C given in parenthesis). Exclusively mitochondrial enzymes: glutamate dehydrogenase (1.8), NAD-isocitrate dehydrogenase (0.5), citrate synthase (5.2), pyruvate carboxylase (3.0); exclusively extramitochondrial enzymes: glucose 6-phosphate dehydrogenase (5.8), 6-phosphogluconate dehydrogenase (5.2), NADP-malate dehydrogenase (11.0), ATP-citrate lyase (5.1); enzymes present in both mitochondrial and extramitochondrial compartments: NADP-isocitrate dehydrogenase (3.7), NAD-malate dehydrogenase (330), aconitate hydratase (1.1), carnitine acetyltransferase (0.4), acetyl-CoA synthetase (1.0), aspartate aminotransferase (1.7), alanine aminotransferase (6.1). The mean DNA content of eight preparations of fat-cells was 109mug/g dry weight of cells. 2. Mitochondria showing respiratory control ratios of 3-6 with pyruvate, about 3 with succinate and P/O ratios of approaching 3 and 2 respectively have been isolated from fat-cells. From studies of rates of oxygen uptake and of swelling in iso-osmotic solutions of ammonium salts, it is concluded that fat-cell mitochondria are permeable to the monocarboxylic acids, pyruvate and acetate; that in the presence of phosphate they are permeable to malate and succinate and to a lesser extent oxaloacetate but not fumarate; and that in the presence of both malate and phosphate they are permeable to citrate, isocitrate and 2-oxoglutarate. In addition, isolated fat-cell mitochondria have been found to oxidize acetyl l-carnitine and, slowly, l-glycerol 3-phosphate. 3. It is concluded that the major means of transport of acetyl units into the cytoplasm for fatty acid synthesis is as citrate. Extensive transport as glutamate, 2-oxoglutarate and isocitrate, as acetate and as acetyl l-carnitine appears to be ruled out by the low activities of mitochondrial aconitate hydratase, mitochondrial acetyl-CoA hydrolyase and carnitine acetyltransferase respectively. Pathways whereby oxaloacetate generated in the cytoplasm during fatty acid synthesis by ATP-citrate lyase may be returned to mitochondria for further citrate synthesis are discussed. 4. It is also concluded that fat-cells contain pathways that will allow the excess of reducing power formed in the cytoplasm when adipose tissue is incubated in glucose and insulin to be transferred to mitochondria as l-glycerol 3-phosphate or malate. When adipose tissue is incubated in pyruvate alone, reducing power for fatty acid, l-glycerol 3-phosphate and lactate formation may be transferred to the cytoplasm as citrate and malate.
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PMID:The intracellular localization of enzymes in white-adipose-tissue fat-cells and permeability properties of fat-cell mitochondria. Transfer of acetyl units and reducing power between mitochondria and cytoplasm. 439 82

Cell biological techniques requiring cells attached to surfaces, such as monolayer cell culture, microspectrofluorometry, and confocal microscopy, have not been readily available for use on adipocytes because they float and tend to lyse when attached to charged non-biological surfaces. A new method for attaching freshly isolated rodent adipocytes to thermanox plastic surfaces using Matrigel (a defined mixture of extracellular matrix components that resembles the basal lamina surrounding adipocytes in vivo) is described. The method takes advantage of an unusual physical characteristic of Matrigel, i.e., that it is a liquid at cold temperatures and a hydrated gel at higher temperatures. To attach the isolated cells, chilled thermanox plastic coverslips were coated with a thin uniform layer of ice-cold Matrigel and inverted into warm floating adipocytes. Adipocytes floated up against the liquid Matrigel and became immediately attached when the Matrigel changed to a gel in response to the warmth of the cells and media. Cell volume measurements of the attached versus freshly isolated cells indicate no significant difference in the centroid cell volume of the attached cells. This indicates that the method does not select for small or large cells. Adipocytes maintained for 6 days in culture did not display any change in their size or differentiated microscopic appearance. The relative concentrations of major proteins in silver-stained SDS-PAGE gels and several differentiation state-dependent proteins, including ATP-citrate lyase, carbonic anhydrase III (CA III), adipocyte lipid binding protein (ALBP), and pyruvate carboxylase, were examined. No significant change was observed in the relative concentrations of these proteins when the matrigel-cultured adipocytes were compared to freshly isolated cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Monolayer cell culture of freshly isolated adipocytes using extracellular basement membrane components. 761 29

We have developed and implemented a model that can predict the positional isotopomer distribution of various hepatic metabolites labeled with [U-13C3]lactate and/or [U-13C3]pyruvate for given relative flux rates through the citric acid cycle and gluconeogenesis reactions. Our model includes (i) isotopic exchange between alpha-ketoglutarate and glutamate, (ii) a reversible isocitrate dehydrogenase reaction, (iii) an active ATP-citrate lyase, and (iv) aspartate and malate shuttles with separate cytosolic and mitochondrial pools for oxaloacetate, malate, and fumarate. A parameter estimation routine fit the mass isotopomer distribution of selected metabolites measured by gas chromatography-mass spectrometry to the model predicted distributions. We fit measured mass isotopomer distributions of phosphoenolpyruvate, citrate, alpha-ketoglutarate, glutamate, and pyruvate isolated from fasted rat livers perfused with [U-13C3]lactate + [U-13C3]pyruvate. This fitting yielded rates which we express relative to that of pyruvate carboxylase: citric acid cycle represented by the irreversible alpha-ketoglutarate dehydrogenase = 0.32; citrate synthase = 0.64; reversal of isocitrate dehydrogenase = 0.52; citrate lyase = 0.33, aspartate shuttle = 0.24, and malate shuttle = 0.44. Rates calculated for the cytosolic and mitochondrial fumarate and malate dehydrogenase reactions are subject to uncertainties as indicated by identifiability analyses. Previous forms of our model that did not include pyruvate kinase, exchange of alpha-ketoglutarate with glutamate, reversibility of isocitrate dehydrogenase, and/or ATP-citrate lyase activity were not as successful at predicting our measured values. This model offers a general tool for studying the regulation of the citric acid cycle and gluconeogenesis and can be readily modified for any 13C-labeled lactate or pyruvate substrate.
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PMID:Modeling of liver citric acid cycle and gluconeogenesis based on 13C mass isotopomer distribution analysis of intermediates. 773 Mar 5

Enterocytes from fasted rabbits make glucose from exogenous fructose and dihydroxyacetone at rates of 180 and 91 nmol/min/10(8) cells but do not make glucose from glycerol, aspartate, malate, lactate, alpha-ketoglutarate, glutamate or glutamine. Total activities of phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase and glucose 6-phosphatase in isolated enterocytes are 0.44, 0.60 and 1.90 mumol/min/10(8) cells, and > or = 95% of carboxykinase activity is intramitochondrial. Enterocytes contain marginal glycerol kinase (0.05 mumol/ min/10(8) cells) and essentially no pyruvate carboxylase activities. Enterocyte mitochondria synthesize citrate from exogenous phosphoenolpyruvate and acetylcarnitine at a rate of 2.40 nmol/min/mg protein. Citrate formation is highly dependent on exogenous HCO3 and inhibited strongly by 3-mercaptopicolinate and 1,2,3-benzenetricarboxylate. Citrate synthesis is stimulated consistently by GDP and significantly so by GTP. Citrate production is unaffected by ADP or ATP. Enterocytes from fasted-refed rabbits contain activities of 0.05, 0.12, 0.39 and 0.56 mumol/min/mg cytosolic protein of ATP:citrate lyase, NADP:malate dehydrogenase, glucose 6-phosphate dehydrogenase and NADP:isocitrate dehydrogenase. Activities of NADP:malate dehydrogenase, glucose 6-phosphate dehydrogenase and NADP:isocitrate dehydrogenase are significantly higher in enterocytes from fasted-refed rabbits than those from fasted rabbits. Mitochondrial phosphoenolpyruvate carboxykinase in enterocytes in vivo could convert glycolysis-derived phosphoenolpyruvate to oxaloacetate that, with acetyl CoA, could form citrate for export to support cytosolic lipogenesis as an activator of acetyl CoA carboxylase, a source of carbon via ATP:citrate lyase and of NADPH via NADP:malate dehydrogenase or NADP:isocitrate dehydrogenase.
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PMID:Synthesis of citrate from phosphoenolpyruvate and acetylcarnitine by mitochondria from rabbit enterocytes: implications for lipogenesis. 946 72


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