Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been hypothesized that some of the functional impairments associated with aging are the result of increasing oxidative damage to mitochondrial DNA that produces defects in oxidative phosphorylation. To test this hypothesis, we examined the enzymes that catalyze oxidative phosphorylation in crude mitochondrial preparations from frontoparietal cortex of 20 rhesus monkeys (5-34 years old). Samples were assayed for complex I, complex II-III, complex IV, complex V, and citrate synthase activities. When enzyme activities were corrected for citrate synthase activities (to account for variable degrees of mitochondrial enrichment), linear regression analysis demonstrated a significant negative correlation of the activities of complex I (p < 0.002) and complex IV (p < 0.03) with age but no significant change in complex II-III or complex V activities. Relative to animals 6.9 +/- 0.9 years old (n = 7), the citrate synthase-corrected activity of complex I was reduced by 17% in animals 22.5 +/- 0.9 years old (n = 6) (p < 0.05) and by 22% in animals 30.7 +/- 0.9 years old (n = 7) (p < 0.01). Similar age-related reductions in the activities of complexes I and IV were obtained when enzyme activities were corrected for complex II-III activity. These findings show an age-associated progressive impairment of mitochondrial complex I and complex IV activities in cerebral cortices of primates.
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PMID:Age-dependent impairment of mitochondrial function in primate brain. 847 11

The heat-shock protein Cpn60 (chaperonin, GroEL homologue) from the phototrophic bacterium Rhodobacter capsulatus B10 was purified to homogeneity and biochemically characterized. Native Cpn60 from R. capsulatus was shown to be a tetradecamer of 840 kDa similar to that of homologous chaperones characterized so far. Cpn60 possesses ATPase activity and promotes refolding of chaotropically denatured citrate synthase. The groESL operon of R. capsulatus was cloned using a degenerate oligonucleotide and sequenced. Two open reading frames (285 and 1,635 bp) were found; they encode Cpn10 and Cpn60, with corresponding deduced molecular masses of 10.6 and 57.6 kDa. The deduced amino acid sequences coincided perfectly with those of the amino terminus and of three tryptic peptides of purified Cpn60 from R. capsulatus. Strong evidence that R. capsulatus encodes only one copy of the groESL operon was obtained. Primer-extension analysis revealed that the groESL operon is transcribed by a -35/-10-type promoter, and that transcription was initiated from the same positions before and after heat-shock under both chemotrophic and phototrophic conditions. The major initiation site is immediately followed by the inverted repeat structure CIRCE, which has been found upstream of many bacterial heat-shock operons. A second minor transcript starts just after the CIRCE element. Although heat-shock induction of a groEL-lacZ fusion failed because of thermal inactivation of the fusion protein, Western blot analysis revealed a two- to threefold induction of cellular Cpn60 levels 45-75 min after shifting from 28 degrees C to 39 degrees C. Deletion mapping of the groESL promoter identified upstream of the promoter a 19-bp element that enhances groESL transcription eightfold and contains the AT-rich sequence dAAATTTTT, which is found at similar positions in heat-shock operons of other gram-negative bacteria.
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PMID:Molecular analysis of the Rhodobacter capsulatus chaperonin (groESL) operon: purification and characterization of Cpn60. 870 96

Specific mitochondrial enzyme activities, mitochondrial DNA copy number, and mRNA levels were measured in heart, brain, and liver tissues of a group of alcohol-fed rats and compared with a control group. The results show a significant increase in mitochondrial enzyme activities (citrate synthase, complex IV, complex III, complex I, and complex V), as well as an increase in mitochondrial DNA in the cardiac tissue of the alcohol-fed animals. These data are indicative of an increase in mitochondrial number in the cardiac tissue that may occur as the result of an adaptive response to the alcoholic insult. However, in the liver and brain of the alcohol-treated rat, specific mitochondrial activities were decreased, in particular, complex III and ATP synthase, whereas levels of other mitochondrial enzymes (e.g., citrate synthase, specific mitochondrial transcripts, and mitochondrial DNA levels) do not seem to be affected. These data suggest that a tissue-specific response to alcohol exists that may have a common molecular mechanism in brain and liver, but is different in the heart.
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PMID:Heart mitochondria response to alcohol is different than brain and liver. 874 11

To determine whether expression of a nuclear gene encoding a mitochondrial fatty acid oxidation enzyme is regulated in parallel with skeletal muscle fibre-type-specific energy substrate preference, expression of the gene encoding medium-chain acyl-CoA dehydrogenase (MCAD) was delineated in canine latissimus dorsi muscle subjected to chronic motor nerve stimulation. In predominantly fast-twitch canine latissimus dorsi muscle, MCAD mRNA levels were regulated by chronic stimulation in a biphasic pattern. During the 1st wk of stimulation, steady-state MCAD mRNA levels decreased to 50% of unstimulated levels. MCAD mRNA levels began to increase during the 3rd wk of stimulation to reach a level 3.0-fold higher than levels in unstimulated contralateral control muscle by day 70. Immunodetectable MCAD mRNA levels throughout the stimulation period. The temporal pattern and magnitude of MCAD mRNA accumulation in response to muscle stimulation was distinct from that of mRNAs encoding other enzymes known to be regulated by this stimulus, including glyceraldehyde phosphate dehydrogenase, citrate synthase, and sarcoplasmic reticulum Ca-ATPase, but paralleled the protein levels of the peroxisome proliferator-activated receptor (PPAR), an orphan member of the nuclear hormone receptor superfamily known to regulate genes encoding fatty acid oxidation enzymes in liver. The skeletal muscle expression pattern of PPAR was also similar to that of MCAD in unstimulated rat skeletal muscles with distinct fiber-type compositions. These results demonstrate that a nuclear gene encoding a mitochondrial beta-oxidation enzyme is dynamically regulated in a pattern that parallels skeletal muscle fiber-type-specific energy substrate utilization and implicate an orphan nuclear receptor transcription factor as a candidate transducer of this response.
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PMID:Activation of a novel metabolic gene regulatory pathway by chronic stimulation of skeletal muscle. 896 42

In the proximal convoluted tubule (PCT) of rat kidney, reabsorption is known to take place during fetal life, but no data on Na-K-ATPase and mitochondrial energy metabolism enzymes in this epithelium were available at fetal and neonatal stages. With use of the quantitative histochemistry approach, Na-K-ATPase, citrate synthase (tricarboxylic acid cycle), 3-ketoacid CoA-transferase and thiolase (ketone body oxidation), beta-hydroxyacyl-CoA dehydrogenase (fatty acid oxidation), and acetylcarnitine transferase (acetyl-CoA transport through mitochondrial membrane) were microassayed in PCT and metanephric mesenchyme of fetal and newborn rat kidney. The data indicate that, during fetal life, PCT differentiation involves concomitant increases in Na-K-ATPase and oxidative enzyme activities, supporting the hypothesis that mitochondria could play an active role in cellular ATP turnover when reabsorptive functions develop. Birth resulted in marked increases in the activities of Na-K-ATPase and of fatty acid and ketone body oxidation enzymes in the PCT, whereas no changes in enzyme activities occurred in the metanephric mesenchyme between the fetal and the newborn stage.
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PMID:Birth-related changes in energy metabolism enzymes and Na-K-ATPase in kidney proximal convoluted tubule cells. 912 12

Bacterial periplasmic substrate-binding proteins are initial receptors in the process of active transport across cell membranes and/or chemotaxis. Each of them binds a specific substrate (e.g. sugar, amino acid, or ion) with high affinity. For transport, each binding protein interacts with a cognate membrane complex consisting of two hydrophobic proteins and two subunits of a hydrophilic ATPase. For chemotaxis, binding proteins interact with specific membrane chemotaxis receptors. We report, herewith, that the oligopeptide-binding protein OppA of Escherichia coli, the maltose-binding protein MalE of E. coli, and the galactose-binding protein MglB of Salmonella typhimurium interact with unfolded and denatured proteins, such as the molecular chaperones that are involved in protein folding and protein renaturation after stress. These periplasmic substrate-binding proteins promote the functional folding of citrate synthase and alpha-glucosidase after urea denaturation. They prevent the aggregation of citrate synthase under heat shock conditions, and they form stable complexes with several unfolded proteins, such as reduced carboxymethyl alpha-lactalbumin and unfolded bovine pancreatic trypsin inhibitor. These chaperone-like functions are displayed by both the liganded and ligand-free forms of binding proteins, and they occur at binding protein concentrations that are 10-100-fold lower than their periplasmic concentration. These results suggest that bacterial periplasmic substrate-binding proteins, in addition to their function in transport and chemotaxis, might be implicated in protein folding and protection from stress in the periplasm.
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PMID:Chaperone properties of the bacterial periplasmic substrate-binding proteins. 918 48

These experiments examined the myosin phenotype and bioenergetic enzyme activities in rat respiratory muscles. Muscle samples were removed from adult female Sprague-Dawley rats (N = 8) and analyzed to determine the myosin heavy chain (MHC) and light chain (MLC) isoform content as well as the activities of myofibrillar ATPase (mATPase), citrate synthase (CS; Krebs cycle enzyme), and lactate dehydrogenase (LDH; glycolytic enzyme). Analysis revealed that CS activity and the % type I MHC and %IId MHC isoforms were greater in the costal diaphragm (CO-D) compared with those in the crural diaphragm (CR-D). In contrast, the % type IIb MHC was higher in the CR-D compared with that in the CO-D. LDH and mATPase activity were lower in both the CO-D and CR-D compared with that in the parasternal intercostals (PI), external intercostals (EI), internal intercostals (II), rectus abdominis (RA), and sternomastoid (SM) muscles. CS activity, % type I MHC, %IIa MHC, and the ratio of slow to total alkali MLC (1s/1s + 1f + 3f) were greater in the CO-D and CR-D compared with those in all other respiratory muscles. The RA contained the highest (P < 0.05) % type IIb MHC and lowest CS activity compared with that in all other muscles. Finally, CS activity, mATPase activity, and MHC phenotype did not differ among the PI, EI, II, and SM muscles. These differences in biochemical properties provide the muscles of the respiratory pump with great versatility in functional properties.
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PMID:Myosin phenotype and bioenergetic characteristics of rat respiratory muscles. 943 89

Little information is presently available concerning mitochondrial respiratory and oxidative phosphorylation function in the normal human heart during growth and development. We investigated the levels of specific mitochondrial enzyme activities and content during cardiac growth and development from the early neonatal period (10-20 days) to adulthood (67 years). Biochemical analysis of enzyme specific activities and content and mitochondrial DNA (mtDNA) copy number was performed with left ventricular tissues derived from 30 control individuals. The levels of cytochrome c oxidase (COX) and complex V specific activity, mtDNA copy number and COX subunit II content remained unchanged in contrast to increased citrate synthase (CS) activity and content. The developmental increase in CS activity paralleled increasing CS polypeptide content, but was neither related to overall increases in mitochondrial number nor coordinately regulated with mitochondrial respiratory enzyme activities. Our findings of unchanged levels of cardiac mitochondrial respiratory enzyme activity during the progression from early childhood to older adult contrasts with the age-specific regulation found with CS, a Krebs cycle mitochondrial enzyme.
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PMID:Human mitochondrial function during cardiac growth and development. 954 45

To examine the effects of unweighting on the structural and metabolic adaptations of a non-postural muscle, deltoideus muscle biopsies were taken in seven male healthy subjects, before and after a 37 day bedrest. Myofibrillar ATPase histochemistry demonstrated no change in fibre type distributions (I, IIA, IIB), in fibre cross-sectional areas nor in capillary supply. No difference was noted in enzyme activities of oxidative metabolism (citrate synthase, 3-hydroxy-acyl-CoA dehydrogenase), and glycolysis (hexokinase, lactate dehydrogenase). Electron microscopy showed a decrease in the volume density of lipids but no change in mitochondrial volume density and distribution. The results indicate that bedrest induces no major morphological and biochemical changes in deltoideus muscle, contrary to what was previously reported in vastus lateralis muscle. This lack of changes is probably related to an unaltered deltoideus muscle use.
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PMID:Effects of bedrest on deltoideus muscle morphology and enzymes. 955 Feb 25

A gene encoding 544 amino acids for a subunit of group II chaperonin (thermosome) was cloned from a thermophilic methanogen, Methanococcus thermolithotrophicus. The deduced amino acid sequence showed 66.5, 56.1, and 20.1% similarities to those of Methanopyrus kandleri and Thermoplasma acidophilum and group I chaperonin of Escherichia coli, respectively. We call this chaperonin MTTS (M. thermolithotrophicus thermosome). The MTTS gene was expressed in E. coli. The purified recombinant MTTS seemed to be monomeric on gel filtration in the absence of Mg2+ and ATP. The monomer assembled to an oligomer (complex) in the presence of 50 mM MgCl2, 0.25 mM ATP, and 0.3 M (NH4)2SO4. It was eluted immediately before the elution volume of E. coli GroEL tetradecamer on gel filtration with a TSKgel G3000SWXL column. This reconstructed MTTS complex showed the cylindrical structure with two stacked rings in electron microscopy. The MTTS complex formed filamentous structures in the presence of Mg2+ and ATP at the protein concentration above 3.0 mg/ml. This filament formation was reversible. The MTTS filament was dissociated to the complex by dilution to the protein concentration of 0.2 mg/ml, even in the presence of Mg2+ and ATP. The MTTS complex exhibited weak ATPase activity with the hydrolysis rate of 74 mol of ATP hydrolysis/mol of MTTS complex/min at 70 degreesC. The MTTS complex promoted the refolding of chemically denatured thermophilic archaeal citrate synthase and glucose dehydrogenase at 50 degreesC in an ATP-dependent fashion. The analysis of nucleotide specificity of chaperone activity of MTTS suggested that it was coupled with hydrolysis of ATP, CTP, or UTP.
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PMID:Group II chaperonin in a thermophilic methanogen, Methanococcus thermolithotrophicus. Chaperone activity and filament-forming ability. 977 67


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