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)

Twelve pairs of healthy sedentary males matched for their body mass index (BMI) with either a low insulin response (LIR; a stage of prediabetes) or a high (HIR; controls) to a standardized glucose infusion test (GIT) were studied in respect to their exercise capacities (W(OBLA), W(SL) and relative W(OBLA):W(OBLA) x W(SL)(-10 x 100), muscle fiber composition (%ST), muscle citrate synthase activity (CS), muscle ubiquinone (MUQ), MUQ over %ST (muscle quality index, MQI), and peripheral insulin sensitivity (PIS) as described with insulin-clamp techniques (SIGITmean). LIR and HIR displayed normal PIS and positive relationships versus exercise capacity. LIR's but not HIR's relative W(OBLA) was related to CS as earlier only documented in endurance athletes but at a lower level than in athletes. This pointed at a poor peripheral oxygen delivery in LIR. LIR's MQI decreased relative to HIR's the higher the muscle CS indicating radical related muscle trauma in LIR as in athletes. LIR representing prediabetes described muscle anomalies, which could represent prestages of the lesions observed in type-2 diabetes. They are claimed to be responsible for insulin-, glucose-, lipid-resistance, and peripheral circulatory resistance.
Mol Cell Biochem 1998 Jan
PMID:Muscle metabolism and quality (MQI) in prediabetic sedentary man. 954 83

Fatty acids are the preferred substrate of ischemic, reperfused myocardium and may account for the decreased cardiac efficiency during aerobic recovery. Neonatal cardiac myocytes in culture respond to hypoxia/serum- and glucose-free medium by a slow decline in ATP which reverses upon oxygenation. This model was employed to examine whether carnitine palmitoyltransferase I (CPT-I) modulates high rates of beta-oxidation following oxygen deprivation. After 5 h of hypoxia, ATP levels decline to 30% control values and CPT-I activity is significantly stimulated in hypoxic myocytes with no alteration in cellular carnitine content or in the release of the mitochondrial matrix marker, citrate synthase. This stimulation was attributed to an increase in the affinity of hypoxic CPT-I for carnitine, suggesting that the liver CPT-I isoform is more dominant following hypoxia. However, there was no alteration in hypoxic CPT-I inhibition by malonyl-CoA. DNP-etomoxiryl-CoA, a specific inhibitor of the liver CPT-I isoform, uncovered identical Michaelis kinetics of the muscle isoform in control and hypoxic myocytes with activation of the liver isoform. Northern blotting did not reveal any change in the relative abundance of mRNA for the liver vs. the muscle CPT-I isoforms. The tyrosine phosphatase inhibitor, pervanadate, reversed the hypoxia-induced activation of CPT-I and returned the affinity of cardiac CPT-I for carnitine to control. Reoxygenation was also associated with a return of CPT-I activity to control levels. The data demonstrate that CPT-I is activated upon ATP depletion. Lower enzyme activities are present in control and reoxygenated cells where ATP is abundant or when phosphatases are inhibited. This is the first suggestion that phosphorylation may modulate the activity of the liver CPT-I isoform in heart.
Mol Cell Biochem 1998 Mar
PMID:The liver isoform of carnitine palmitoyltransferase I is activated in neonatal rat cardiac myocytes by hypoxia. 954 43

We have investigated the effect of chronic exposure of rats to an hypoxic environment (10% O2; 3 weeks), on the first step of the intracellular energy transfer process in the myocardium, i.e. the transfer at mitochondrial level of high energy bonds from ATP to creatine. In the left ventricles from rats adapted to normobaric hypoxia, we observed, using the permeabilized fiber technique, that the stimulatory effect of creatine on the mitochondrial respiration in presence of a low ADP concentration (0.1 mM) was attenuated when compared to control. Furthermore, the creatine-induced decrease of the apparent K(m) for ADP of the mitochondrial respiration, which is observed in control, was significantly reduced. Both the basal and maximal respiratory rates of the fibers were unchanged by the hypoxic exposure of the rats. A significant decrease of the total creatine kinase activity from 755 to 630 IU/g wet weight (for control and hypoxic rats, respectively) was detected and was accompanied by a 25% decrease in mitochondrial isoform activity (mitoCK) and in the mitoCK/citrate synthase ratio. In the right ventricles, identical alterations in the effect of creatine on apparent K(m) for ADP were observed while we did not detect any changes in CK activity. The decrease in mitoCK activity and the fall in the reactivity of respiration to creatine could be interpreted as a mechanism for downregulating oxygen demand during chronic hypoxia. The consequences of such alterations on energy metabolism of cardiomyocytes under conditions of reduced oxygen supply are discussed.
J Mol Cell Cardiol 1998 Jul
PMID:Chronic exposure of rats to hypoxic environment alters the mechanism of energy transfer in myocardium. 971 Jul 98

We used the minitransposon TnhlyAs [Gentschev, I., Maier, G., Kranig, A. and Goebel, W. (1996) Mol. Gen. Genet. 252, 266-274] for random insertion of the secretion signal (HlyAs) of Escherichia coli hemolysin (HlyA) into chromosomal genes. Four mini-TnhlyAs derivatives bearing the gltA (citrate synthase), deoC (2 deoxyribose-5 phosphate aldolase), tig (trigger factor) genes and an unknown ORF fused to hlyAs were identified and characterized. Our data suggest that TnhlyAs-generated hemolysin fusion proteins are secreted efficiently by the HlyB/HlyD/TolC hemolysin secretion machinery and that this can be useful for studies of gene expression or function.
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PMID:Construction of chromosomally encoded secreted hemolysin fusion proteins by use of mini-TnhlyAs transposon. 971 56

Muscle deconditioning is a common observation in patients with congestive heart failure (CHF), chronic obstructive pulmonary disease, neuromuscular diseases or prolonged bed rest. To gain further insight into metabolic and mechanical properties of deconditioned slow-twitch (soleus) or fast-twitch (EDL) skeletal muscles, we induced experimental muscle deconditioning by hindlimb suspension (HS) in rats for 3 weeks. Cardiac muscle was also studied. Besides profound muscle atrophy, increased proportion of fast type II fibers as well as fast myosin isoenzymes, we found decreased calcium sensitivity of Triton X-100 skinned fiber bundles of soleus muscle directed towards the fast muscle phenotype. Glycolytic enzymes such as hexokinase and pyruvate kinase were increased, and the LDH isoenzyme pattern was clearly shifted from an oxidative to an anaerobic profile. Creatine kinase (CK) and myokinase activities were increased in HS soleus towards EDL values. Moreover, the M-CK mRNA level was greatly increased in soleus, with no change in EDL. However, oxygen consumption rate assessed in situ in saponin skinned fibers (12.5 +/- 0.8 in C and 15.1 +/- 0.9 micromol O2/min/g dw in HS soleus compared to 7.3 +/- 1.3 micromol O2/min/g dw in control EDL), as well as mitochondrial CK (mi-CK) and citrate synthase activities, were preserved in HS soleus. Following deconditioning no change in Km for ADP of mitochondrial respiration, either in the absence (511 +/- 92 in C and 511 +/- 111 microM in HS soleus compared to 9 +/- 4 microM in control EDL) or presence of creatine (88 +/- 10 in C and 95 +/- 16 microM in HS soleus compared to 32 +/- 9 microM in control EDL), was found. The results show that muscle deconditioning induces a biochemical and functional slow to fast phenotype transition in myofibrillar and cytosolic compartments of postural muscle, but not in the mitochondrial compartment, suggesting that these compartments are differently regulated under conditions of decreased activity.
J Mol Cell Cardiol 1998 Nov
PMID:Muscle unloading induces slow to fast transitions in myofibrillar but not mitochondrial properties. Relevance to skeletal muscle abnormalities in heart failure. 992 74

Total and peroxisomal palmitate oxidation capacities and mitochondrial enzyme activities were compared in tissues from growing rats, preruminant calves and 15-month-old bulls. Total palmitate oxidation rates were 1.9-5.2-fold higher in rat than in bovine tissues and 1.7-fold higher in the heart and muscles from calves than from growing bulls. The peroxisomal contribution to palmitate oxidation was similar between rats and bovines (i.e. calves and bulls) in liver (35-51%), heart (26%) but not in muscles (14 +/- 3% in rats vs 33 +/- 4.5% in bovines, P < 0.05). Mitochondrial enzyme activities were 1.8-4.8-fold higher in rat than in bovine tissues but the citrate synthase to cytochrome-c oxidase ratio was the highest in the liver (17-38), intermediate in the heart and muscles from calves and rats (6-10) and the lowest in heart and muscles from bulls (2-3, P < 0.05). In all tissues and animal groups, palmitate oxidation rates were similar per unit cytochrome-c oxidase activity, but not always per unit citrate synthase activity. Therefore, differences in mitochondrial contents (as between rats and bovines) or in mitochondrial characteristics (as between liver and muscles) relate to the differences in palmitate oxidation capacity.
Comp Biochem Physiol B Biochem Mol Biol 1998 Oct
PMID:Contribution of mitochondria and peroxisomes to palmitate oxidation in rat and bovine tissues. 997 94

Examination of the ways side-chain carboxylate and amide groups in high-resolution protein crystal structures form hydrogen bonds with main-chain atoms reveals that the most common category is a two-hydrogen-bond four to five residue motif with an aspartate or asparagine (Asx) at the first residue, for which we propose the name Asx-motif. Similar motifs with glutamate or glutamine residues at that position are rare. Asx-motifs occur typically as (1) a common feature of the N termini of alpha-helices called the Asx N-cap motif; (2) an independent motif, usually a beta-turn with an appropriately hydrogen-bonded Asx as the first residue; and (3) a motif incorporated in a beta-bulge loop. Asx-motifs are common, there being just under two-and-a-half in an average-sized protein subunit; of these, about 55 % are Asx N-cap motifs. Because they occur often in many situations, it seems that these motifs have an inherent propensity to form on their own rather than just being a feature stabilised at the end of a helix. Asx-motifs also occur in functionally interesting situations in aspartyl proteases, citrate synthase, EF hands, haemoglobins, lipocalins, glutathione reductase and the alpha/beta hydrolases.
J Mol Biol 1999 Mar 12
PMID:A natural grouping of motifs with an aspartate or asparagine residue forming two hydrogen bonds to residues ahead in sequence: their occurrence at alpha-helical N termini and in other situations. 1006 20

We report a new type of fatal mitochondrial disorder caused by selective deficiency of mitochondrial ATP synthase (ATPase). A hypotrophic newborn from a consanguineous marriage presented severe lactic acidosis, cardiomegaly and hepatomegaly and died from heart failure after 2 days. The activity of oligomycin-sensitive ATPase was only 31-34% of the control, both in muscle and heart, but the activities of cytochrome c oxidase, citrate synthase and pyruvate dehydrogenase were normal. Electrophoretic and western blot analysis revealed selective reduction of ATPase complex but normal levels of the respiratory chain complexes I, III and IV. The same selective deficiency of ATPase was found in cultured skin fibroblasts which showed similar decreases in ATPase content, ATPase hydrolytic activity and level of substrate-dependent ATP synthesis (20-25, 18 and 29-33% of the control, respectively). Pulse-chase labelling of patient fibroblasts revealed low incorporation of [(35)S]methionine into assembled ATPase complexes, but increased incorporation into immunoprecipitated ATPase subunit beta, which had a very short half-life. In contrast, no difference was found in the size and subunit composition of the assembled and newly produced ATPase complex. Transmitochondrial cybrids prepared from enucleated fibroblasts of the patient and rho degrees cells derived from 143B. TK(-)human osteosarcoma cells fully restored the ATPase activity, ATP synthesis and ATPase content, when compared with control cybrids. Likewise, the pattern of [(35)S]methionine labelling of ATPase was found to be normal in patient cybrids. We conclude that the generalized deficiency of mitochondrial ATPase described is of nuclear origin and is caused by altered biosynthesis of the enzyme.
Hum Mol Genet 1999 Oct
PMID:A novel deficiency of mitochondrial ATPase of nuclear origin. 1048 64

Prior studies have shown that partial outlet obstruction of the rabbit bladder causes a progressive increase in bladder mass, a progressive decrease in the contractile response to different forms of stimulation, and a selective decrease in the activity of mitochondrial enzymes. In this investigation the contractile responses to field stimulation and bethanechol were directly correlated with the activity of citrate synthase as a function of both the duration of obstruction and the bladder mass. Partial bladder outlet obstruction was surgically induced in twenty New Zealand White rabbits. The bladders were then rapidly excised at 30, 40, 90, 105 or 150 days post obstruction. The contractile responses to field stimulation (32 Hz) and bethanechol (250 microM) were determined. The remainder of the bladders were frozen and used for citrate synthase activity determinations. The data were grouped for analysis both by the duration of obstruction and by the bladder mass. Chronic partial outlet obstruction caused a parallel decline in the activity of citrate synthase and in the response of the obstructed tissue to stimulation.
Mol Cell Biochem 1999 Oct
PMID:Metabolic basis for contractile dysfunction following chronic partial bladder outlet obstruction in rabbits. 1056 77

HtrA, which has a high molecular mass of about 500 kDa, is a periplasmic heat shock protein whose proteolytic activity is essential for the survival of Escherichia coli at high temperatures. To determine the structural organization of HtrA, we have used electron microscopy and chemical cross-linking analysis. The averaged image of HtrA with end-on orientation revealed a six-membered, ring-shaped structure with a central cavity, and its side-on view showed a two-layered structure. Thus, HtrA behaves as a dodecamer consisting of two stacks of hexameric ring. HtrA can degrade thermally unfolded citrate synthase and malate dehydrogenase but cannot when in their native form. HtrA degraded partially unfolded casein more rapidly upon increasing the incubation temperature. However, it hydrolyzed oxidized insulin B-chain, which is fully unfolded, at nearly the same rate at all of the temperatures tested. HtrA also rapidly degraded reduced insulin B-chain generated by treatment of insulin with dithiothreitol but not A-chain or intact insulin. Moreover, HtrA degraded fully unfolded alpha-lactalbumin, of which all four disulfide bonds were reduced, but not the native alpha-lactalbumin and its unfolded intermediates containing two or three disulfide bonds. These results indicate that unfolding of the protein substrates, such as by exposure to high temperatures or reduction of disulfide bonds, is essential for their access into the inner chamber of the double ring-shaped HtrA, where cleavage of peptide bonds may occur. Thus, HtrA with a self-compartmentalizing structure may play an important role in elimination of unfolded proteins in the periplasm of Escherichia coli.
J Mol Biol 1999 Dec 17
PMID:Selective degradation of unfolded proteins by the self-compartmentalizing HtrA protease, a periplasmic heat shock protein in Escherichia coli. 1060 Mar 91


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