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)

The activities (Vmax) of hexokinase, glycogen phosphorylase, glucose-6-phosphate dehydrogenase, phosphofructokinase, lactate dehydrogenase, citrate synthase, cytochrome c oxidase, and 3-OH-acyl-CoA dehydrogenase in human skeletal muscles were compared with the in vitro utilization of glucose and palmitic acid assessed under optimal conditions. Statistically significant correlations between substrate fluxes and enzyme activities were found suggesting that the substrate incorporation rate in vitro in some way reflects the capacity of metabolic pathways. The incorporation rate of leucine into muscle proteins was also statistically significantly correlated to the RNA concentration in the muscle tissue. Glycolytic and glycogenolytic enzymes correlated significantly to each other and correlations were also found between aerobic enzymes supporting the validity of constant proportions between certain key enzymes in human skeletal muscles.
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PMID:Incorporation rate of glucose carbon, palmitate carbon and leucine carbon into metabolites in relation to enzyme activities and RNA levels in human skeletal muscles. 17 28

Fatty acid synthetase was covalently labelled with [14C]palmitic acid from [14C]palmityl-CoA. Tryptic and peptic digestion of the [14C]palmityl enzyme resulted in the formation of radioactive palmityl peptides carrying the long-chain acyl residue both in oxygen-ester and thio-ester linkage. The lipophilic palmityl peptides were purified by column and thin-layer chromatography using organic lolvent systems. Peptides arising from the acyl carrier protein, the condensing enzyme and the palmityl transferase were identified and characterized. The amino acid sequence of a 4'-phosphopant-etheine-containing peptide was established. It comprises 13 residues and shows a high degree of homology with the acyl carrier protein from Escherichia coli. A heptapeptide and an octapeptide from the palmityl transferase active site were partially sequenced. The identical amino acid composition of palmityl transferase and malonyl transferase core peptides is briefly discussed.
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PMID:The palmityl binding sites of fatty acid synthetase from yeast. 33 65

To evaluate the peroxisomal requirement for beta-oxidation of hydroxyeicosatetraenoic acids (HETES), we tested 5-, 12- and 15-HETE oxidation in wild-type and mutant Chinese hamster ovary (CHO) cells. Mutant CHO cells contain peroxisomal ghosts, have random cytosolic localization of catalase and lack two of the enzymes necessary for peroxisomal beta-oxidation. Reverse-phase HPLC indicated that 33% of 12-HETE radioactivity was converted by wild-type CHO cells during a 2 h incubation to one major and several minor polar metabolites. Wild-type CHO cells also converted 15-HETE to one major and several minor polar metabolites. Neither 12- nor 15-HETE were converted to any metabolites by the mutant CHO cell lines, despite appreciable cellular uptake of these hydroxyeicosanoids. 5-HETE was not converted to any metabolic products by either the wild-type or the mutant CHO cells. Docosahexaenoic acid beta-oxidation was substantially reduced in the mutants as compared to the wild-type cells, palmitic acid beta-oxidation was reduced to an intermediate extent in the mutants, but octanoate beta-oxidation and citrate synthase activity were not impaired. Protein immunoblotting for mitochondrial manganese superoxide dismutase indicated a single band of identity at 20 kDa in both wild-type and mutant CHO cells. Since mutant CHO cells fail to convert 12- and 15-HETE to oxidative metabolites but contain normal mitochondrial enzymatic activities, intact peroxisomes appear to be the organelle responsible for HETE oxidation.
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PMID:Hydroxyeicosatetraenoic acid oxidation in Chinese hamster ovary cells: a peroxisomal metabolic pathway. 189 74

1. Palmitate oxidation rates and activities of creatine kinase, cytochrome c oxidase and citrate synthase were determined in homogenates of three different human muscles and their derived muscle cell cultures. Palmitate oxidation was also assayed in intact cultured cells (myotubes). 2. Biopsies obtained from m. rectus abdominis exhibited a lower palmitate oxidation rate and lower activities of citrate synthase and cytochrome c oxidase than those from m. gluteus and m. quadriceps. In contrast, cell cultures obtained from the three muscles were mutually comparable with regard to these mitochondrial activities. 3. Although cell cultures only reached a low differentiation grade (judged by the total creatine kinase activity and percentage isoenzyme-MM) they are well comparable with the original biopsies with respect to citrate synthase activity and capacity of palmitate oxidation. The activity of cytochrome c oxidase was clearly lower in the cultured cells. 4. Palmitate was more completely oxidized in intact myotubes than in homogenates of myotubes. Apparent Km and Vmax values of palmitate oxidation did not differ significantly in homogenates and intact preparations of myotubes.
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PMID:Palmitate oxidation and some enzymes of energy metabolism in human muscles and cultured muscle cells. 342 77

Human muscle cell cultures were examined for capacities to oxidize several substrates, and for activities of some enzymes related to intermediate metabolism. The results indicate that mitochondrial activities attained appreciable degrees of maturity. The specific activity of creatine kinase increased during myoblast fusion. In contrast, parameters of oxidative metabolism (palmitate and pyruvate oxidation, and cytochrome c oxidase and citrate synthase) did not significantly change throughout myogenesis and thereafter. In differentiated cells (myotubes) the oxidation capacities were pyruvate greater than 2-oxoglutarate greater than malate (+ acetylcarnitine) greater than malate (+ pyruvate), as in muscle biopsies. With regard to protein the cultured human muscle cells showed higher activities than the original biopsies (= 100%) with respect to citrate synthase (179%), but lower values for cytochrome c oxidase (50%) and creatine kinase (7%). Palmitate oxidation capacities were the same in both systems. The presence of antimycin and rotenon inhibited to a comparable extent the palmitate oxidation in cultured muscle and biopsies.
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PMID:Oxidative metabolism of cultured human skeletal muscle cells in comparison with biopsy material. 396 49

Actual and total branched-chain 2-oxo acid dehydrogenase activities were determined in homogenates of incubated diaphragms from fed and starved rats. Incubation in Krebs-Ringer buffer increased the activity state, but caused considerable loss of total activity. Palmitate oxidation rates and citrate synthase activities did not significantly change on incubation. Starved muscles showed a higher extent of activation after 15 min of incubation (not after 30 and 60 min) and a smaller loss of total activity. Experiments with the transaminase inhibitor amino-oxyacetate confirm that the contribution of endogenous amino acids to the oxidation precursor pool is also smaller in diaphragms from starved rats on incubation in vitro. These phenomena together cause the higher 14CO2 production from 14C-labelled branched-chain amino acids and 2-oxo acids in muscles from starved than from fed rats. High concentrations of branched-chain 2-oxo acids, and the presence of 2-chloro-4-methyl-pentanoate, octanoate or ketone bodies, increase the extent of activation of the dehydrogenase complex; glucose and pyruvate had no effect. The observed changes of the activity state by these metabolites are discussed in relation to their interaction with branched-chain 2-oxo acid oxidation in incubated hemidiaphragms.
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PMID:Increase of the activity state and loss of total activity of the branched-chain 2-oxo acid dehydrogenase in rat diaphragm during incubation. 651 61

The evaluating of palmitate oxidation in muscle tissue may be a useful screening test for detecting defects in fatty acid metabolism in human neuromuscular disease. If the test is to be useful, it is necessary to obtain data on a wide variety of muscle illnesses for comparative purposes. We report our experience with palmitate oxidation, muscle carnitine, and carnitine palmityl transferase (CPT) activity in 148 muscles biopsies from a variety of illnesses. The efficacy of using total protein, citrate synthase, and (1-14C) pyruvate oxidation as internal references was investigated. Palmitate oxidation was significantly less than normal (P less than or equal to 0.01) in Duchenne muscular dystrophy, congenital nonprogressive myopathy, congenital muscular dystrophy, malignant hyperpyrexia, and denervation, depending on the internal reference used. Muscle carnitine levels followed a similar pattern, however, CPT activity did not. The possibility of these findings being secondary to inactivity is discussed.
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PMID:Palmitate oxidation in human muscle: comparison to CPT and carnitine. 708 21

Intramuscular lipid pool turnover [triacylglycerols (TG), phospholipids (PL), mono- and diacylglycerols (MG, DG)] and the oxidation of endogenous and exogenous lipids were determined with pulse-chase studies in incubated muscles of varied oxidative potential [soleus strips (SOL)--> epitrochlearis --> flexor digitorum brevis]. Incorporation of palmitate into TG and PL pools and its oxidation were linearly related to time and exogenous palmitate concentration in all muscles. Total palmitate incorporation (deposition and oxidation) was greatest in SOL. However, palmitate incorporation into TG was similar in all muscles when expressed as a percentage of the total incorporation. In contrast, palmitate incorporation into PL was greatest in the least oxidative muscle. Palmitate oxidation, incorporation into TG, and citrate synthase activity were all strongly correlated with muscle cytosolic fatty acid-binding protein content (r = 0.96, 1.0, and 0.98, respectively). During the chase, reducing exogenous palmitate from 1.0 mM to 0.5 or 0 mM resulted in a significant (approximately 30%) loss of [(14)C]palmitate from the TG pool in SOL and a significant increase in (14)CO(2) production from endogenous stores. No significant loss of (14)C label from lipid pools occurred in the less oxidative muscles, suggesting a closely regulated interaction between energy provision from exogenous and endogenous lipid pools in oxidative muscle. Glucose oxidation increased significantly in all muscles in the absence of palmitate. The loss of (14)C label from TG in SOL during the chase without palmitate was not accompanied by a significant change in TG content. This suggests that, during rest, there is a small subpool of TG with a relatively rapid turnover.
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PMID:Functional differences in lipid metabolism in resting skeletal muscle of various fiber types. 912 37

We examined the effects of 8 wk of intense endurance training on free fatty acid (FFA) transporters and metabolism in resting and contracting soleus muscle using pulse-chase procedures. Endurance training increased maximal citrate synthase activity in red muscles (+54 to +91%; P </= 0.05) but failed to increase cytosolic fatty acid binding protein content, mRNA for fatty acyl-CoA synthase, and the putative FFA transporters or transport of palmitic acid into giant sarcolemmal vesicles. At rest, only triacylglycerol (TG) synthesis was significantly increased by training (+100.9 +/- 8.7 vs. +66.6 +/- 6.7 nmol/g wet wt; P </= 0.05). Muscle contraction increased TG synthesis (+46%; P </= 0.05) and palmitate oxidation (+115%; P </= 0.05) in untrained rats. Endurance training further enhanced synthesis of monoacylglycerol (MG), diacylglycerol (DG) and TG during contraction (+36, +69 and +71%, respectively; P </= 0.05), as well as exogenous palmitate oxidation (+41%; P </= 0.05) relative to untrained rats. Compared with those in untrained rats, TG breakdown and oxidation during contraction were reduced after training by 49 and 30%, respectively (P </= 0.05). In conclusion, endurance training 1) increases FFA oxidation and incorporation into endogenous lipid pools during contraction and 2) reduces the rate of intramuscular TG utilization during contraction when exogenous FFA availability is adequate. The enhanced FFA uptake subsequent to training appears to be independent of altered maximal transport rates of FFA into the muscle cell.
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PMID:Endurance training increases FFA oxidation and reduces triacylglycerol utilization in contracting rat soleus. 1078 Sep 32

The purpose of this study was to discern cellular mechanisms that contribute to the suppression of lipid oxidation in the skeletal muscle of obese individuals. Muscle was obtained from obese [body mass index (BMI), 38.3 +/- 3.1 kg/m(2)] and lean (BMI, 23.8 +/- 0.9 kg/m(2)) women, and fatty acid oxidation was studied by measuring (14)CO(2) production from (14)C-labeled fatty acids. Palmitate oxidation, which is at least partially dependent on carnitine palmitoyltransferase-1 (CPT-1) activity, was depressed (P < 0.05) by approximately 50% with obesity (6.8 +/- 2.2 vs. 13.7 +/- 1.4 nmole CO(2).g(-1).h(-1)). The CPT-1-independent event of palmitoyl carnitine oxidation was also depressed (P < 0.01) by approximately 45%. There were significant negative relationships (P < 0.05) for adiposity with palmitate (r = -0.76) and palmitoyl carnitine (r = -0.82) oxidation. Muscle CPT-1 and citrate synthase activity, an index of mitochondrial content, were also significantly (P < 0.05) reduced ( approximately 35%) with obesity. CPT-1 (r = -0.48) and citrate synthase (r = -0.65) activities were significantly (P < 0.05) related to adiposity. These data suggest that lesions at CPT-1 and post-CPT-1 events, such as mitochondrial content, contribute to the reduced reliance on fat oxidation evident in human skeletal muscle with obesity.
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PMID:Lipid oxidation is reduced in obese human skeletal muscle. 1105 58


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