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)

Previous studies in our laboratory demonstrated significant changes in bovine heart mitochondrial bioenergetics during fetal growth and development. To further understand mitochondrial biogenesis in early human development, the activity and subunit content levels of specific mitochondrial enzymes in fetal and neonatal heart were determined. Comparing early gestation (EG, 45-65 day) later gestation (LG, 85-110 day) and neonate (birth-1 month), specific activity of citrate synthase (CS), a Krebs cycle enzyme showed a 2 fold increase from EG to LG and a 2 fold increase from LG to neonate. Specific activities of complex IV and complex V increased similarly 1.8-2 fold from EG to LG. However during the later fetal period from LG to neonate, complex IV activity increased only 1.3 fold and complex V showed no significant increase. Peptide content of COX-II subunit increased 2 fold from EG to LG and by 3.5 fold from LG to neonate. Levels of COX-IV and ATP synthase alpha subunits were undetectable in EG hearts, clearly detectable in LG heart and 3 fold increased from LG to neonate. Unexpectedly, mitochondrial transcription factor A (mt-TFA) levels were not significantly different during these developmental stages. Mitochondrial DNA (mtDNA) levels increased 1.8 fold from EG to LG, and 3.8 fold increase from EG to neonate and correlated with CS activity levels. In conclusion, these data indicate coordinated regulation of some nuclear-encoded (COX-IV and CS activity) and mitochondrial components (COX-II and mtDNA), and strongly suggest that mitochondrial content increases particularly during the early fetal cardiac development and reveal a distinct pattern of regulation for mt-TFA.
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PMID:Heart mitochondrial DNA and enzyme changes during early human development. 1097 57

IscU, a NifU-like Fe/S-escort protein, binds to and stimulates the ATPase activity of Hsc66, a hsp70-type molecular chaperone. We present evidence that stimulation arises from interactions of IscU with the substrate-binding site of Hsc66. IscU inhibited the ability of Hsc66 to suppress the aggregation of the denatured model substrate proteins rhodanese and citrate synthase, and calorimetric and surface plasmon resonance measurements showed that ATP destabilizes Hsc66.IscU complexes in a manner expected for hsp70-substrate complexes. Studies on the interaction of IscU with Hsc66 truncation mutants further showed that IscU does not bind the isolated ATPase domain of Hsc66 but does bind and stimulate a mutant containing the ATPase domain and substrate binding beta-sandwich subdomain. These results support a role for IscU as a substrate for Hsc66 and suggest a specialized function for Hsc66 in the assembly, stabilization, or transfer of Fe/S clusters formed on IscU.
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PMID:The Fe/S assembly protein IscU behaves as a substrate for the molecular chaperone Hsc66 from Escherichia coli. 1105 47

Intrinsic changes in skeletal muscle are being increasingly suspected as part of the underlying cause of exercise intolerance in patients with chronic heart failure (CHF). The objective of the present study was to determine whether differences existed between CHF patients and age-matched healthy controls in the concentration of skeletal muscle Na(+)-K(+)-ATPase (adenosine triphosphatase), a cation pump that functions to restore Na(+)-K(+) gradients and protect membrane excitability. Moreover, given the potency for physical activity in altering long-term regulation of the pump, an additional objective was to examine the role of activity level in pump expression in CHF patients. Na(+)-K(+)-ATPase concentration (pmol/g wet wt) determined in the vastus lateralis muscle of 27 CHF males (ejection fraction, 23 +/- 1.6%), using the vanadate facilitated [(3)H] ouabain binding technique, was not different (264 +/- 10) from 10 sedentary controls (268 +/- 19,P > 0.05). Similarly, no differences (P > 0.05) could be found between female patients (228 +/- 16, n = 7) and controls (243 +/- 13, n = 9). Differences between untrained control (294 +/- 20, n = 7), chronically active (251 +/- 20, n = 9), and trained (252 +/- 16, n = 6) CHF groups in Na(+)-K(+) pump expression were also insignificant. This study indicates that long-term regulation of Na(+)-K(+)-ATPase concentration is not altered in moderate CHF patients, regardless of the history of regular activity. However, the positive correlations (P < 0.05) that were observed between peak aerobic power (VO(2) peak) and Na(+)-K(+)-ATPase (r = 0.422) and VO(2) peak and maximal citrate synthase activity (r = 0.404) suggests a role for the skeletal muscle in explaining exercise intolerance in CHF patients.
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PMID:Normal skeletal muscle Na(+)-K(+) pump concentration in patients with chronic heart failure. 1115 Sep 68

Thermogenic capabilities of red-winged blackbirds improve markedly during their 10-12-day nestling period, especially between day 5 and day 8. The time course of improvements may be determined by the maturation of skeletal muscles involved in shivering thermogenesis, particularly the pectoralis muscles. To test this hypothesis, morphological and biochemical changes in pectoral and leg muscles were measured in young and adult blackbirds. Both muscles grew disproportionately relative to body mass. The pectoralis consisted entirely of fast-twitch fibers, predominantly fast oxidative glycolytic. In contrast, the gastrocnemius muscle consisted of a mixture of slow and fast fibers (predominantly fast glycolytic). Although fiber composition was constant, both cross-sectional area and density of fibers increased with age in both muscles. Catabolic capacities of the pectoralis increased significantly (approximately 7-8-fold) throughout the nestling period, most abruptly after day 3 (citrate synthase, CS) or day 4 (3-hydroxacyl-CoA-dehydrogenase, HOAD). Myofibrillar ATPase activities in the pectoralis were initially low, but increased after day 5. Further increases in CS and myofibrillar ATPase activities occurred in the pectoralis after fledging. CS and HOAD activities in the leg were much lower, but myofibrillar ATPase activities were remarkably similar in the two muscles, differing only in adults. These results are consistent with the hypothesis that the development of endothermy is dependent on the morphological and biochemical maturation of skeletal muscles important in thermogenesis.
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PMID:Ontogeny of catabolic and morphological properties of skeletal muscle of the red-winged blackbird (Agelaius phoeniceus). 1168 11

As in many other fleshy fruits, the predominant organic acids in ripe peach (Prunus persica (L.) Batsch) fruit are malic and citric acids. The accumulation of these metabolites in fruit flesh is regulated during fruit development. Six peach fruit-related genes implicated in organic acid metabolism (mitochondrial citrate synthase; cytosolic NAD-dependent malate dehydrogenase, and cytosolic NADP-dependent isocitrate dehydrogenase) and storage (vacuolar proton translocating pumps: one vacuolar H+-ATPase, and two vacuolar H+-pyrophosphatases) were cloned. Five of these peach genes were homologous to genes isolated from fruit in other fleshy fruit species. Phylogenetic and expression analyses suggested the existence of a particular vacuolar pyrophosphatase highly expressed in fruit. The sixth gene was the first cytosolic NAD-dependent malate dehydrogenase gene isolated from fruit. Gene expression was studied during the fruit development of two peach cultivars, a normal-acid (Fantasia) and a low-acid (Jalousia) cultivar. The overall expression patterns of the organic acid-related genes appeared strikingly similar for the two cultivars. The genes involved in organic acid metabolism showed a stronger expression in ripening fruit than during the earlier phases of development, but their expression patterns were not necessarily correlated with the changes in organic acid contents. The tonoplast proton pumps showed a biphasic expression pattern more consistent with the patterns of organic acid accumulation, and the tonoplast pyrophosphatases were more highly expressed in the fruit of the low-acid cultivar during the second rapid growth phase of the fruit.
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PMID:Isolation and characterization of six peach cDNAs encoding key proteins in organic acid metabolism and solute accumulation: involvement in regulating peach fruit acidity. 1190 73

A mechanism decreasing oxidative metabolism during normal cell division and growth is expected to direct substrates toward biosyntheses rather than toward complete oxidation to CO(2). Hence, any event decreasing oxidative phosphorylations (OXPHOS) could provide a proliferating advantage to a transformed or tumor cell in an oxidative tissue. To test this hypothesis, we studied mitochondrial enzymes, DNA and OXPHOS protein content in three types of renal tumors from 25 patients. Renal cell carcinomas (RCCs) of clear cell type (CCRCCs) originate from the proximal tubule and are most aggressive. Chromophilic RCCs, from similar proximal origin, are less aggressive. The benign renal oncocytomas originate from collecting duct cells. Mitochondrial enzyme and DNA contents in all tumor types or grades differed significantly from normal tissue. Mitochondrial impairment increased from the less aggressive to the most aggressive RCCs, and correlated with a considerably decreased content of OXPHOS complexes (complexes II, III, and IV of the respiratory chain, and ATPase/ATP synthase) rather than to the mitochondrial content (citrate synthase and mitochondrial (mt)DNA). In benign oncocytoma, some mitochondrial parameters (mtDNA, citrate synthase, and complex IV) were increased 4- to 7-fold, and some were slightly increased by a factor of 2 (complex V) or close to normal (complexes II and III). A low content of complex V protein was found in all CCRCC and chromophilic tumors studied. However F(1)-ATPase activity was not consistently decreased and its impairment was associated with increased aggressiveness in CCRCCs. Immunodetection of free F(1)-sector of complex V demonstrated a disturbed assembly/stability of complex V in several CCRCC and chromophilic tumors. All results are in agreement with the hypothesis that a decreased OXPHOS capacity favors faster growth or increased invasiveness.
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PMID:Low mitochondrial respiratory chain content correlates with tumor aggressiveness in renal cell carcinoma. 1201 48

The use of tamoxifen (TAM) has been questioned on the chemotherapy and chemoprevention of breast cancer due to several estrogen receptor-independent cytotoxic effects. As an alternative, its more active metabolite 4-hydroxytamoxifen (OHTAM) has been proposed with presumed lower side effects. In this work, the potential OHTAM toxicity on rat liver mitochondrial bioenergetics in relation to the multiple deleterious effects of TAM was evaluated. OHTAM, at concentrations lower than those putatively reached in tissues following the administration of TAM, does not induce significant perturbations on the respiratory control ratio (RCR), ADP/O, transmembrane potential (DeltaPsi), phosphorylative capacity and membrane integrity of mitochondria. However, at high concentrations, OHTAM depresses the DeltaPsi, RCR and ADP/O, affecting the phosphorylation efficiency, as also inferred from the DeltaPsi fluctuations and pH changes associated with ADP phosphorylation. Moreover, OHTAM, at concentrations that stimulate the rate of state 4 respiration in parallel to the decrease in the DeltaPsi and phosphorylation rate, causes mitochondrial swelling and stimulates both ATPase and citrate synthase activities. However, the OHTAM-observed effects, at high concentrations, are not significant relatively to the damaging effects promoted by TAM and suggest alterations to mitochondrial functions due to proton leak across the mitochondrial inner membrane.
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PMID:4-Hydroxytamoxifen induces slight uncoupling of mitochondrial oxidative phosphorylation system in relation to the deleterious effects of tamoxifen. 1227 May 94

The aims of this study were (i) to assess the differences between men and women in maximal activities of selected enzymes of aerobic and anaerobic pathways involved in skeletal muscle energy production, and (ii) to assess the relationships between maximal enzyme activities, body composition, muscle cross-sectional area (CSA) and fibre type composition. Muscle biopsies were obtained from the tibialis anterior (TA) muscle of 15 men and 15 women (age 20-31 years) with comparable physical activity levels. The muscle CSA was determined by magnetic resonance imaging (MRI). Maximal activities of lactate dehydrogenase (LDH), phosphofructokinase (PFK), beta-hydroxyacyl-coenzyme A dehydrogenase (HAD), succinate dehydrogenase (SDH) and citrate synthase (CS), were assayed spectrophotometrically. The proportion, mean area and relative area (proportion x area) of type 1 and type 2 fibres were determined from muscle biopsies prepared for enzyme histochemistry [myofibrillar adenosine triphosphatase (mATPase)]. The men were significantly taller (+6.6%; P < 0.001) and heavier (+19.1%; P < 0.001), had significantly larger muscle CSA (+19.0%; P < 0.001) and significantly larger areas and relative areas of both type 1 and type 2 fibres (+20.5-31.4%; P = 0.007 to P < 0.001). The men had significantly higher maximal enzyme activities than women for LDH (+27.6%; P = 0.007) and PFK (+25.5%; P = 0.003). There were no significant differences between the men and the women in the activities of HAD (+3.6%; ns), CS (+21.1%; P = 0.084) and SDH (+7.6%; ns). There were significant relationships between height and LDH (r = 0.41; P = 0.023), height and PFK (r = 0.41; P = 0.025), weight and LDH (r = 0.45; P = 0.013), and weight and PFK (r = 0.39; P = 0.032). The relationships were significant between the muscle CSA and the activities of LDH (r = 0.61; P < 0.001) and PFK (r = 0.56; P = 0.001), and between the relative area of type 2 fibres and the activities of LDH (r = 0.49; P = 0.006) and PFK (r = 0.42; P = 0.023). There were no significant relationships between HAD, CS and SDH, and height, weight, muscle CSA and fibre type composition, respectively. These data indicate that the higher maximal activities of LDH and PFK in men are related to the height, weight, muscle CSA and the relative area of type 2 fibres, which are all significantly larger in men than women.
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PMID:Enzyme activities in the tibialis anterior muscle of young moderately active men and women: relationship with body composition, muscle cross-sectional area and fibre type composition. 1239 1

We have cloned, purified to homogeneity, and characterized as a molecular chaperone the Escherichia coli YedU protein. The purified protein shows a single band at 31 kDa on SDS-polyacrylamide gels and forms dimers in solution. Like other chaperones, YedU interacts with unfolded and denatured proteins. It promotes the functional folding of citrate synthase and alpha-glucosidase after urea denaturation and prevents the aggregation of citrate synthase under heat shock conditions. YedU forms complexes with the permanently unfolded protein, reduced carboxymethyl alpha-lactalbumin. In contrast to DnaK/Hsp70, ATP does not stimulate YedU-dependent citrate synthase renaturation and does not affect the interaction between YedU and unfolded proteins, and YedU does not display any peptide-stimulated ATPase activity. We conclude that YedU is a novel chaperone which functions independently of an ATP/ADP cycle.
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PMID:Characterization of the Escherichia coli YedU protein as a molecular chaperone. 1256 79

We report the characterization of the first chaperonin (Mm-cpn) from a mesophilic archaeon, Methanococcus maripaludis. The single gene was cloned from genomic DNA and expressed in Escherichia coli to produce a recombinant protein of 543 amino acids. In contrast with other known archaeal chaperonins, Mm-cpn is fully functional in all respects under physiological conditions of 37 degrees C. The complex has Mg(2+)-dependent ATPase activity and can prevent the aggregation of citrate synthase. It promotes a high-yield refolding of guanidinium-chloride-denatured rhodanese in a nucleotide-dependent manner. ATP binding is sufficient to effect folding, but ATP hydrolysis is not essential.
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PMID:Nucleotide-dependent protein folding in the type II chaperonin from the mesophilic archaeon Methanococcus maripaludis. 1262


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