Gene/Protein Disease Symptom Drug Enzyme Compound
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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)

Citrate synthase and cytochrome c increase in soleus muscle of rats in response to excess thyroid hormones. The half times of the increase in the levels of citrate synthase and cytochrome c in soleus muscle during induction are greater than the half times of the decline in enzyme levels after cessation of treatment (15 days vs. 7 days for citrate synthase). Denervation of the soleus does not prevent the increase in citrate synthase in response to thyrotoxicosis. This provides evidence that thyroid hormones affect the muscle directly and not via the motor nerves. ATP concentration is reduced in liver, but not in soleus muscle in response to thyrotoxicosis. Creatine phosphate is not significantly altered in soleus muscle. Cyclic AMP is slightly lower in thyrotoxic soleus muscle. Simultaneous treatment with thyroid hormones and propranolol does not affect the increase in citrate synthase in response to excess thyroid hormones. It is concluded that the increase in muscle mitochondria associated with thyrotoxicosis is not mediated via the nervous system or by a cAMP-regulated process.
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PMID:Time course of the T3- and T4-induced increase in rat soleus muscle mitochondria. 21 61

Much has been learned about FACES of the endoplasmic reticulum since its discovery in the early 1960s. FACES consists of four component reactions, requires the fatty acid to be activated in the form of a CoA derivative, utilizes reducing equivalents in the form of NADH or NADPH, is induced by a fat-free diet, resides on the cytoplasmic surface of the endoplasmic reticulum, appears to function in concert with the desaturase system and appears to exist in multiple forms (either multiple condensing enzymes connected to a single pathway or multiple pathways). FACES has been found in all tissues investigated, namely, liver, brain, kidney, lung, adrenals, retina, testis, small intestine, blood cells (lymphocytes and neutrophils) and fibroblasts, with one exception--the heart has no measurable activity. Yet, much more needs to be learned. The critical, inducible and rate-limiting condensing enzyme has resisted solubilization and purification; the purification of the other components has met with limited success. We know nothing about the site of synthesis of each component of FACES. How is each component enzyme integrated into the endoplasmic reticulum membrane? Is there a single mRNA directing synthesis of all four components or are there four separate mRNAs? How are elongation and desaturation coordinated? What is (are) the physiological regulator(s) of FACES--ADP, AMP, IP3, G-proteins, phosphorylation, CoA, Ca2+, cAMP, none of these? The molecular biology of FACES is only in the fetal stage of development. We are only scratching the surface--it is an undiscovered country.
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PMID:The fatty acid chain elongation system of mammalian endoplasmic reticulum. 164 95

A transcript analysis of the citrate synthase and succinate dehydrogenase genes (gltA-sdhCDAB) of Escherichia coli was done by nuclease S1 mapping. Evidence was obtained for two monocistronic gltA transcripts extending anti-clockwise, to a common terminus, from independent promoters with start points 196 bp (major) and 299 bp (minor) upstream of the gltA coding region. Evidence was also obtained for two polycistronic sdh transcripts, sdhCDAB (minor) and sdhDAB (major), extending clockwise, from sites 219 bp upstream of sdhC and 1455 bp upstream of sdhD (i.e. within sdhC), to a common terminus. The synthesis of all of the transcripts was repressed by growth in the presence of glucose, and this is consistent with the well-established fact that both enzymes are subject to catabolite repression. Sequences resembling known binding sites for the cAMP-CRP (cyclic AMP-cyclicAMP receptor protein) complex occur in the vicinity of each promoter suggesting that they are activated by the cAMP-CRP complex.
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PMID:Transcript analysis of the citrate synthase and succinate dehydrogenase genes of Escherichia coli K12. 330 32

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

Thirty-two female Sprague-Dawley rats were assigned to one of four groups: control (CON); exercise training (TR); exercise training + clenbuterol treatment (0.8 mg kg body wt(-1) d(-1)) (TR + CL) or exercise training + clenbuterol treatment + 2% beta-guanidinoproprionic acid diet (TR + CL + beta) to examine whether alterations in the high energy phosphate state of the muscle mediates exercise training-induced increases in skeletal muscle GLUT4 protein concentration and citrate synthase activity. Exercise training consisted of running the rats 5 d week(-1) for 8 weeks on a motor-driven treadmill (32 m min(-1), 15% grade). Gastrocnemius GLUT4 protein concentration and citrate synthase activity were significantly elevated in the TR animals, but these adaptations were attenuated in the TR + CL animals. Providing beta-GPA in combination with clenbuterol enabled training to elevate GLUT4 protein concentration and citrate synthase activity, with the increase in GLUT4 being greater than that observed for the TR animals. Skeletal muscle ATP levels were reduced in the TR + CL + beta animals while ATP levels in the TR + CL animals were significantly elevated compared with CON. An acute 40-min bout of electrical stimulation of the sciatic nerve was found to lower skeletal muscle ATP levels by approximately 50% and elevate cAMP levels in all groups. No difference in post-contraction cAMP levels were observed among groups. However, post-contraction ATP levels in the TR + CL animals were significantly greater than the other groups. Collectively, these findings suggest that exercise training-induced increases in skeletal muscle GLUT4 protein concentration and citrate synthase activity are initiated in response to a reduction in the skeletal muscle ATP concentration.
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PMID:Attenuating the decline in ATP arrests the exercise training-induced increases in muscle GLUT4 protein and citrate synthase activity. 1007

In Saccharomyces cerevisiae the Ras/cAMP/PKA signalling pathway controls multiple metabolic pathways, and alterations in the intracellular concentrations of cAMP through modification of signalling pathway factors can be lethal or result in severe growth defects. In this work, the important role of Ras2p in metabolic regulation during growth on the non-fermentable carbon source glycerol is further investigated. The data show that the overexpression of RAS2 suppresses the growth defect of the glyoxylate cycle citrate synthase mutant, cit2Delta. The overexpression results in enhanced proliferation and biomass yield when cells are grown on glycerol as sole carbon source, and increases citrate synthase activity and intracellular citrate concentration. Interestingly, the suppression of cit2Delta and the enhanced proliferation and biomass yield are only observed when RAS2 is overexpressed and not in strains containing the constitutively active allele RAS2(val19). However, both RAS2 and RAS2(val19)upregulated citrate synthase activity. We propose that the RAS2 overexpression results in a combination of general upregulation of respiratory growth capacity and an increase in mitochondrial citrate/citrate synthases, which together, complement the metabolic requirements of the cit2Delta mutant. The data therefore provide new evidence for the role of Ras2p as a powerful modulator of metabolism during growth on a non-fermentable carbon source.
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PMID:Regulation of respiratory growth by Ras: the glyoxylate cycle mutant, cit2Delta, is suppressed by RAS2. 1683 79

Saccharopolyspora erythraea has three citrate synthases encoded by gltA-2, citA, and citA4. Here, we characterized and identified the expression and regulatory properties of these synthases. Three pleiotropic global regulatory proteins of S. erythraea - CRP, GlnR, and DasR - are involved in carbon metabolism, nitrogen metabolism, and amino-sugar (chitin and GlcNAc) metabolism. Using electrophoretic mobility shift assays (EMSAs), we identified these regulators as proteins that bind directly to the promoter regions of all citrate synthase genes (gltA-2, citA, and citA4). Footprinting assays indicated the exact protect sequences of CRP, GlnR, and DasR on the promoter region of gltA-2, revealing binding competition between GlnR and DasR. Moreover, by comparing the transcription levels of citrate synthase genes between parental and glnR mutant or dasR mutant strains, or by comparing the transcription response of citrate synthases under various nutrient conditions, we found that GlnR and DasR negatively regulated citA and citA4 transcription but had no regulatory effects on the gltA-2 gene. Although no CRP mutant was available, the results indicated that CRP was a cAMP-binding receptor affecting gltA-2 transcription when the intracellular cAMP concentration increased. Thus, an overall model of CS regulation by C and/or N metabolism regulators and cAMP receptor protein was proposed.
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PMID:Three genes encoding citrate synthases in Saccharopolyspora erythraea are regulated by the global nutrient-sensing regulators GlnR, DasR, and CRP. 2529 17

A positional isomer of 3',5'-cAMP, 2',3'-cAMP, is produced by kidneys in response to energy depletion, and renal 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) metabolizes 2',3'-cAMP to 2'-AMP; 2',3'-cAMP is a potent opener of mitochondrial permeability transition pores (mPTPs), which can stimulate autophagy. Because autophagy protects against AKI, it is conceivable that inhibition of CNPase protects against ischemia-reperfusion (IR) -induced AKI. Therefore, we investigated renal outcomes, mitochondrial function, number, area, and autophagy in CNPase-knockout (CNPase(-/-)) versus wild-type (WT) mice using a unique two-kidney, hanging-weight model of renal bilateral IR (20 minutes of ischemia followed by 48 hours of reperfusion). Analysis of urinary purines showed attenuated metabolism of 2',3'-cAMP to 2'-AMP in CNPase(-/-) mice. Neither genotype nor IR affected BP, heart rate, urine volume, or albumin excretion. In WT mice, renal IR reduced (14)C-inulin clearance (index of GFR) and increased renal vascular resistance (measured by transit time nanoprobes) and urinary excretion of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. IR did not affect these parameters in CNPase(-/-) mice. Histologic analysis revealed that IR induced severe damage in kidneys from WT mice, whereas histologic changes were minimal after IR in CNPase(-/-) mice. Measurements of renal cardiolipin levels, citrate synthase activity, rotenone-sensitive NADH oxidase activity, and proximal tubular mitochondrial and autophagosome area and number (by transmission electron microscopy) indicted accelerated autophagy/mitophagy in injured CNPase(-/-) mice. We conclude that CNPase deletion attenuates IR-induced AKI, in part by accelerating autophagy with targeted removal of damaged mitochondria.
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PMID:Renal 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase Is an Important Determinant of AKI Severity after Ischemia-Reperfusion. 2657 47