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Query: EC:2.3.3.1 (citrate synthase)
 4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. In epididymal adipose tissue synthesizing fatty acids from fructose in vitro, addition of insulin led to a moderate increase in fructose uptake, to a considerable increase in the flow of fructose carbon atoms to fatty acid, to a decrease in the steady-state concentration of lactate and pyruvate in the medium, and to net uptake of lactate and pyruvate from the medium. It is concluded that insulin accelerates a step in the span pyruvate-->fatty acid. 2. Mitochondria prepared from fat-cells exposed to insulin put out more citrate than non-insulin-treated controls under conditions where the oxaloacetate moiety of citrate was formed from pyruvate by pyruvate carboxylase and under conditions where it was formed from malate. This suggested that insulin treatment of fat-cells led to persistent activation of pyruvate dehydrogenase. 3. Insulin treatment of epididymal fat-pads in vitro increased the activity of pyruvate dehydrogenase measured in extracts of the tissue even in the absence of added substrate; the activities of pyruvate carboxylase, citrate synthase, glutamate dehydrogenase, acetyl-CoA carboxylase, NADP-malate dehydrogenase and NAD-malate dehydrogenase were not changed by insulin. 4. The effect of insulin on pyruvate dehydrogenase activity was inhibited by adrenaline, adrenocorticotrophic hormone and dibutyryl cyclic AMP (6-N,2'-O-dibutyryladenosine 3':5'-cyclic monophosphate). The effect of insulin was not reproduced by prostaglandin E(1), which like insulin may lower the tissue concentration of cyclic AMP (adenosine 3':5'-cyclic monophosphate) and inhibit lipolysis. 5. Adipose tissue pyruvate dehydrogenase in extracts of mitochondria is almost totally inactivated by incubation with ATP and can then be reactivated by incubation with 10mm-Mg(2+). In this respect its properties are similar to that of pyruvate dehydrogenase from heart and kidney where evidence has been given that inactivation and activation are catalysed by an ATP-dependent kinase and a Mg(2+)-dependent phosphatase. Evidence is given that insulin may act by increasing the proportion of active (dephosphorylated) pyruvate dehydrogenase. 6. Cyclic AMP could not be shown to influence the activity of pyruvate dehydrogenase in mitochondria under various conditions of incubation. 7. These results are discussed in relation to the control of fatty acid synthesis in adipose tissue and the role of cyclic AMP in mediating the effects of insulin on pyruvate dehydrogenase.
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PMID:Regulation of adipose tissue pyruvate dehydrogenase by insulin and other hormones. 515 98

Cells of the aerotolerant anaerobe Giardia lamblia respire in the presence of oxygen. Endogenous respiration is stimulated by glucose but not by other carbohydrates and Krebs cycle intermediates. Endogenous and glucose-stimulated respiration are insensitive to cyanide, malonate, and 2,4-dinitrophenol, but are inhibited by atabrin and iodoacetamide. G. lamblia produces ethanol, acetate and CO2 both aerobically and anaerobically either from endogenous reserves or exogenous glucose. Molecular hydrogen is not produced. The following enzyme activities were detected in homogenates: hexokinase, fructose-biphosphate aldolase, pyruvate kinase, phosphoenolpyruvate carboxykinase, malate dehydrogenase, malate dehydrogenase (decarboxylating), pyruvate synthase, acetyl-CoA synthetase, alcohol dehydrogenase (NADP+), NADH dehydrogenase, NADPH dehydrogenase, NADPH oxidoreductase and superoxide dismutase. The enzymes of energy and carbohydrate metabolism are nonsedimentable (109 000 x g for 30 min). Activities of lactate dehydrogenase, hydrogenase, phosphate acetyltransferase, acetate kinase, citrate synthase, succinate dehydrogenase, fumarate hydratase and catalase were below the limits of detection. The results suggest the occurrence of glycolysis, energy production by substrate level phosphorylation and a flavin, iron-sulfur protein mediated electron transport system as well as the absence of cytochrome mediated oxidative phosphorylation and functional Krebs cycle.
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PMID:Energy metabolism of the anaerobic protozoon Giardia lamblia. 610 7

Aldosterone-dependent changes in citrate synthase (CS) activity have been used as an index of mineralocorticoid target sites. However, adrenalectomy (ADX) resulted in a fall in activity of CS and several other enzymes in rabbit heart, a tissue with glucocorticoid-but not mineralocorticoid-specific receptors. The enzymes included CS (2.03-1.36 U/mg protein, normal----ADX, P less than 0.001), isocitrate dehydrogenase-NADP+ (1.10-0.80 U/mg, P less than 0.002), isocitrate dehydrogenase-NAD+ (0.034-0.020 U/mg, P less than 0.01), and hydroxymethylglutaryl-CoA lyase (0.072 to 0.035 U/mg, P less than 0.001); in contrast, mitochondrial malate dehydrogenase levels were not significantly reduced by adrenal loss. There was also a decrease after surgery in sarcolemmal Na-K-(17.30-12.31 mumol Pi . mg protein-1 . h-1, P less than 0.002) and Mg-ATPase activities (14.16-12.11 mumol Pi . mg protein-1 . h-1, P less than 0.05). However, ADX did not result in a significant change in heart weight per kilogram body weight or recovery of mitochondrial protein per gram heart. CS was also assayed in hearts from ADX animals following acute (90 min) and chronic (3 day) steroid replacement. Although neither acute intravenous aldosterone (10 micrograms/kg) nor dexamethasone (100 micrograms/kg) increased activity, exposure to multiple subcutaneous injections of either steroid over a 3-day period significantly elevated CS above ADX values. The coordinate changes in the levels of several myocardial enzymes associated with energy metabolism is discussed in terms of an adaptation to chronic alterations in energy demands as opposed to specific mineralocorticoid or glucocorticoid receptor-mediated processes.
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PMID:Influence of adrenalectomy and steroid replacement on heart citrate synthase levels. 614 77

The activities of NAD-specific and NADP-specific isocitrate dehydrogenases were measured in early and term human placenta. In both tissues the activity of NADP-specific isocitrate dehydrogenase was severalfold higher than that of the NAD-dependent enzyme. Subcellular distribution of these two enzymes in the placental tissue was estimated. About 60% of the total NADP-specific isocitrate dehydrogenase activity was found in the mitochondrial fraction and about 40% in the cytosol fraction. Insignificant amounts of the total activity were bound to the microsomal fraction. The whole of the NAD-specific isocitrate dehydrogenase activity was localized in the mitochondrial fraction. The total mitochondrial NADP-specific isocitrate dehydrogenase activity in both early and term placenta was also estimated from the mitochondrial specific activity of this enzyme and the amount of mitochondrial protein in wet tissue, calculated from the activities of citrate synthase or cytochrome c oxidase assayed in the isolated mitochondrial fraction and in the tissue of early and term human placenta.
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PMID:Subcellular distribution of isocitrate dehydrogenase in early and term human placenta. 631 Nov 81

The sub-cellular localisation of enzymes has been defined by latency analysis, and fractionation by differential centrifugation, in cell-free extracts prepared from the mycelium of Aspergillus nidulans by growth in the presence of 2-deoxyglucose followed by treatment with a mixture of beta-glucuronidase, sulphatase and beta-glucanase and exposure to N2 cavitation at 5.2 PMa. In such extracts pyruvate carboxylase and NAD-dependent and NADP-dependent glutamate dehydrogenases are exclusively localised in the cytosol whereas all the other enzymes studied have sub-cellular localisation patterns similar to those described for mammalian liver. Electrophoretic analysis has established the presence of unique mitochondrial and cytosolic isoenzymes for many of the enzymes, e.g. NAD--malate dehydrogenase, NADP--isocitrate dehydrogenase, glutamate/oxaloacetate transaminase, fumarase, which show a marked extent of incomplete latency and the presence of significant activity in the mitochondrial and cytosolic fractions prepared by differential centrifugation. A novel method is described for detection of citrate synthase activity following electrophoresis of the cell-free extract. Application of this method confirms the absence of a unique cytosolic isoenzyme of citrate synthase and hence shows that citrate synthase activity detected in the soluble fraction results from damage to the mitochondria during isolation. A scheme is proposed on the basis of these data to describe the organisation of lipid and amino acid synthesis from glucose in an organism which possesses a cytosolic pyruvate carboxylase.
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PMID:The sub-cellular localisation of pyruvate carboxylase and of some other enzymes in Aspergillus nidulans. 634 55

The binding of two similar spin-labeled fatty acyl-CoA analogues, one short chain, 6-doxyloctanoyl-CoA (S-(2-(5-carboxybutyl)-2-ethyl-4, 4-dimethyl-3-oxazolidinyl-N-oxyl)-CoA) and one long chain, 6-doxylstearoyl-CoA (S-(2-(5-carboxybutyl)-2-dodecyl-4, 4-dimethyl-3-oxazolidinyl-N-oxyl)-CoA) to pig heart citrate synthase (citrate oxaloacetate-lyase (pro-3S-CH2COO- leads to acetyl-CoA) EC 4.1.3.7) has been compared. The binding of the short chain analogue could be satisfactorily fit by a classical treatment (independent, noninteracting sites) with well defined stoichiometry: 2 mol of spin label bound per mol of dimeric enzyme. Binding of the long chain analogue was complex and in excess of 2 mol/dimer. Competitive binding experiments using either analogue in the presence of various nucleotides and substrates revealed differences in the binding of the long and short chain analogues. These additional studies, together with kinetic measurements, implied isosteric binding of acyl-CoA, ATP, NADPH, NADH, NADP+, acetyl-CoA, and partial isosteric binding of the long chain acyl-CoA. Binding of NADPH and NADP+ to the same form of the enzyme, perhaps through overlapping sites, was kinetically verified even though these nucleotides had differing effects on the binding of the spin-labeled analogues. Oxalacetate was shown to decrease the binding of the long chain analogue but to have no effect on the binding of the short chain. This result was supported by kinetic measurements. The competitive binding experiments with the long chain analogue suggested that its complex isotherm resulted from binding in two classes of sites, i.e. two cooperative nucleotide sites and other sites. An empirical mathematical model employing this rationale provided a satisfactory fit for the binding of fatty acyl-CoA to citrate synthase. A spin-labeled fatty acid which was not bound by the native enzyme was appreciably bound in the presence of additional palmitoyl-CoA. This binding might be identified with one of the two sets of binding sites proposed in the model. These and previous results on acyl-CoA binding were correlated with the properties of the CoA binding site defined crystallographically (Remington, S., Wiegand, G., and Huber, R. (1982) J. Mol. Biol. 158, 111-152).
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PMID:Regulation of enzymes by fatty acyl coenzyme A. Interactions of short and long chain spin-labeled acyl-CoA with the acetyl-CoA site on pig heart citrate synthase. 669 13

The activity of 22 enzymes of energy metabolism was determined in m. vastus lateralis quadricipitis of 14 adolescents aged 13-15 years (7 girls) and 14 adults aged 22 to 42 years (7 female subjects). The measurements were performed kinetically, at 37 degrees C, using optimal or near-to-optimal procedures. With the exception of one enzyme, enolase, no differences between sexes were observed in the two age groups. Glycolytic enzymes, including fructose-6-phosphate kinase, showed no significant differences in their activity in adults as compared to adolescents. The activity of enolase was lower in females of both age groups, but no difference due to age was found in this respect. Of the oxidative enzymes studied, only citrate synthase showed no significant difference in adults vs adolescents, whereas the activities of lipoamide dehydrogenase (+ 40%), NADP-isocitrate dehydrogenase (+ 44%), fumarase (+ 24.5%), total malate dehydrogenase (+ 42.2%) and NADH-dehydrogenase (+ 39%) were all significantly higher in the latter group. Aspartate aminotransferase was also 44% higher in adolescents. The possible physiological importance of these observations is discussed with regard to the functional capacity of the skeletal muscle. The hypothesis was considered that adolescents of this age may have a glycolytic capacity comparable to adults, but that they may oxidize pyruvate at a rate higher than adults.
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PMID:Enzyme activities in skeletal muscle of 13-15 years old adolescents. 705 78

The developmental and senescent patterns of a number of heart enzyme activities linked to energy metabolism have been studied in rats aged between 4 days and 21 months. A morphometric study of mitochondrial volume fractions and numbers has been also carried out. Developmental changes result in a rise of most mitochondrial enzymes (NADP+-isocitrate dehydrogenase, malic enzyme, succinate dehydrogenase, citrate synthase) and mitochondrial volume fractions. Exceptions are NAD+-isocitrate dehydrogenase, which declines from 4 days onwards, and NAD+-malate dehydrogenase, which declines and then rises over the same period. Senescent changes follow two different trends. While pyruvate kinase and those mitochondrial enzymes lying between citrate formation and isocitrate oxidation (citrate synthase, NADP+-and NAD+-isocitrate dehydrogenases) decline to some degree, mitochondrial succinate dehydrogenase and NAD+-malate dehydrogenase activities increase over the same period. This could point towards a partial impairment of Krebs cycle function, and a reduced energy-producing capacity in the aged rat heart.
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PMID:Comparison between developmental and senescent changes in enzyme activities linked to energy metabolism in rat heart. 726 74

Activities of citrate synthase, aconitase, NAD- and NADP-dependent isocitrate dehydrogenases were studied in mitochondria of heart and skeletal muscles of embryos and adult rabbits. Activity of these enzymes was some times lower in embryonal skeletal muscles as compared with the muscles of adult animals. Differences in activities of citrate synthase, aconitase and NADP-dependent isocitrate dehydrogenase were unsignificant in heart muscles of embryos and adult animals. Activity of NAD-dependent isocitrate dehydrogenase was distinctly higher in embryonal heart than in adult rabbits. The kinetic parameters enabled to conclude that in vitro regulation of NAD-dependent oxidation of isocitrate by substrate and activator ADP, characteristic for the enzyme from tissues of adult animals, was also found in embryos.
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PMID:[Enzymes of citrate and isocitrate conversion in the heart and skeletal muscle mitochondria of embryos and adult rabbits]. 742 88

The purpose of this study was to investigate whether vitamin D3 deficiency and 1,25-dihydroxyvitamin D3 treatment affect some aspects of heart metabolism in the rat. To this end, five experimental groups were studied: (1) the control group of the vitamin D3 supplemented rats (Group A); (2) rachitic rats (Group B); (3) rachitic rats treated with 1,25-dihydroxyvitamin D3 (Group C); (4) rats fed a vitamin D-deficient diet (Group D); (5) rats fed a vitamin D-deficient diet and treated with 1,25-dihydroxyvitamin D3 (Group E). The five groups were compared by checking in the heart some metabolic parameters, i.e. citrate content, and enzyme activities in cytosol and mitochondria. Citrate content was higher in the heart of treated animals when compared with the control. As regards the enzymatic activities in heart mitochondria, NAD(+)-dependent isocitrate dehydrogenase remarkably decreased in Group B rats and 1,25-dihydroxyvitamin D3 restored quite normal values. NADP(+)-dependent isocitrate dehydrogenase decreased in Group B and Group D animals, and 1,25-dihydroxyvitamin D3 treatment was effective in restoring control values. Cytochrome c oxidase activity did not change, while citrate synthase showed an increase in all the treated rats. As regards the cytosolic enzymes, fructose-6-phosphate kinase increased in the two groups of vitamin D-deplete rats in comparison with the control. Glyceraldehyde-3-phosphate dehydrogenase and 3-phosphoglycerate kinase showed a similar trend: an increase in all the treated animals. In heart homogenate, acylphosphatase and acid phosphatase activities were also determined. Acylphosphatase increased in the treated rats, while acid phosphatase decreased in the rats injected with 1,25-dihydroxyvitamin D3. These results support the hypothesis of a participation of 1,25-dihydroxyvitamin D3 in some aspects of heart metabolism.
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PMID:Effect of vitamin D deficiency and 1,25-dihydroxyvitamin D3 on rat heart metabolism. 789 66


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