Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Proteolytic activities in bovine adrenocortical mitochondria were investigated using [14C-methyl]casein as a substrate. Washed mitochondria showed a low proteolytic activity at pH 7.5 or 8.2. ATP (5 mM) plus MgCl2 (7.5 mM) stimulated the proteolysis 9 times at pH 8.2. It was further demonstrated unequivocally by various approaches that the ATP-dependent proteolytic activity localizes in mitochondrial matrix. The activity of the solubilized protease was sensitive to N-ethylmaleimide, mersalyl acid, phenylmethylsulfonyl fluoride, o-vanadate, m-vanadate, vanadyl sulfate, and quercetin but not by oligomycin and ouabain. The ATP-dependent proteolytic activity was eluted at the position of 650,000 daltons on an Ultrogel AcA 22 column as a single symmetrical peak. The gel-filtered enzyme showed high specificity to ATP. GTP and UTP partially substituted ATP. ADP, AMP, tripolyphosphate, alpha, beta-methylene ATP, and beta, gamma-methylene ATP had little or no stimulating activity. ATP did not stimulate the activity in the absence of MgCl2. We measured ATP-dependent proteolytic activities in mitochondrial fractions from several tissues in rat and bovine. Adrenal cortex was one of the tissues of highest activity. In addition, we investigated the effect of adrenal atrophy on the ATP-dependent protease activity in rat adrenal. The ATP-dependent protease activity/adrenal decreased by dexamethasone treatment. The extent of the decrease was similar to that of cytochrome oxidase and succinate dehydrogenase, but smaller than that of cytochrome P-450.
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PMID:ATP-dependent protease in bovine adrenal cortex. Tissue specificity, subcellular localization, and partial characterization. 298 96

1. The particulate form of lactating bovine mammary lactose synthetase activity is shown to be more highly organized than previously reported. 2. A novel method of shattering frozen mammary tissue with effective cell disruption is described. 3. The apparent subcellular distribution of lactose synthetase was shown to reflect the method of homogenization. 4. After mild homogenization particles associated with a high content of intact lactose synthetase activity sedimented in the lysosome size range between 5x10(4) and 3x10(5)g-min. 5. Lactose synthetase was dissociated and solubilized by VirTis homogenization and ultrasonic treatment. The activities and behaviour of UDP-galactose hydrolase, succinate dehydrogenase, beta-glucuronidase and phosphodiesterase I were compared. 6. Inhibition of UDP-galactose hydrolase by UTP and alpha-lactalbumin was observed.
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PMID:The lactose synthetase particles of lactating bovine mammary gland. Preparation of particles with intact lactose synthetase. 430 May 6

A particulate fraction consisting of heavy organelles such as nuclei and mitochondria was prepared from Ehrlich ascites tumor cells. From this fraction we have purified a GTP-binding protein with a molecular mass of 33 kDa (MTG33) by guanidine hydrochloride extraction followed by four steps of column chromatography. The Kd value of MTG33 for GTP was 17 nM. [alpha-32P]GTP-binding to MTG33 was inhibited by GTP and GDP, but not appreciably by ATP, CTP, UTP, or GMP. MTG33 hydrolyzed GTP to GDP at a rate of 4.5 mmol/min/mol protein. Subcellular fractionation analysis of mouse liver revealed that the heavy mitochondrial fraction contained the highest level of MTG33. Furthermore, dual immunofluorescence examination indicated that the staining of NIH 3T3 cells with anti-MTG33 antibody is coincident with the distribution of mitochondrial succinate dehydrogenase. Of the mouse organs examined, the heart contained the highest level of MTG33. These results strongly suggest that MTG33 is a GTP-binding protein located in mitochondria.
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PMID:Purification of a GTP-binding protein localized in mitochondria. 811 21

Physiologically, a postprandial glucose rise induces metabolic signal sequences that use several steps in common in both the pancreas and peripheral tissues but result in different events due to specialized tissue functions. Glucose transport performed by tissue-specific glucose transporters is, in general, not rate limiting. The next step is phosphorylation of glucose by cell-specific hexokinases. In the beta-cell, glucokinase (or hexokinase IV) is activated upon binding to a pore protein in the outer mitochondrial membrane at contact sites between outer and inner membranes. The same mechanism applies for hexokinase II in skeletal muscle and adipose tissue. The activation of hexokinases depends on a contact site-specific structure of the pore, which is voltage-dependent and influenced by the electric potential of the inner mitochondrial membrane. Mitochondria lacking a membrane potential because of defects in the respiratory chain would thus not be able to increase the glucose-phosphorylating enzyme activity over basal state. Binding and activation of hexokinases to mitochondrial contact sites lead to an acceleration of the formation of both ADP and glucose-6-phosphate (G-6-P). ADP directly enters the mitochondrion and stimulates mitochondrial oxidative phosphorylation. G-6-P is an important intermediate of energy metabolism at the switch position between glycolysis, glycogen synthesis, and the pentose-phosphate shunt. Initiated by blood glucose elevation, mitochondrial oxidative phosphorylation is accelerated in a concerted action coupling glycolysis to mitochondrial metabolism at three different points: first, through NADH transfer to the respiratory chain complex I via the malate/aspartate shuttle; second, by providing FADH2 to complex II through the glycerol-phosphate/dihydroxy-acetone-phosphate cycle; and third, by the action of hexo(gluco)kinases providing ADP for complex V, the ATP synthetase. As cytosolic and mitochondrial isozymes of creatine kinase (CK) are observed in insulinoma cells, the phosphocreatine (CrP) shuttle, working in brain and muscle, may also be involved in signaling glucose-induced insulin secretion in beta-cells. An interplay between the plasma membrane-bound CK and the mitochondrial CK could provide a mechanism to increase ATP locally at the KATP channels, coordinated to the activity of mitochondrial CrP production. Closure of the KATP channels by ATP would lead to an increase of cytosolic and, even more, mitochondrial calcium and finally to insulin secretion. Thus in beta-cells, glucose, via bound glucokinase, stimulates mitochondrial CrP synthesis. The same signaling sequence is used in the opposite direction in muscle during exercise when high ATP turnover increases the creatine level that stimulates mitochondrial ATP synthesis and glucose phosphorylation via hexokinase. Furthermore, this cytosolic/mitochondrial cross-talk is also involved in activation of muscle glycogen synthesis by glucose. The activity of mitochondrially bound hexokinase provides G-6-P and stimulates UTP production through mitochondrial nucleoside diphosphate kinase. Pathophysiologically, there are at least two genetically different forms of diabetes linked to energy metabolism: the first example is one form of maturity-onset diabetes of the young (MODY2), an autosomal dominant disorder caused by point mutations of the glucokinase gene; the second example is several forms of mitochondrial diabetes caused by point and length mutations of the mitochondrial DNA (mtDNA) that encodes several subunits of the respiratory chain complexes. Because the mtDNA is vulnerable and accumulates point and length mutations during aging, it is likely to contribute to the manifestation of some forms of NIDDM.(ABSTRACT TRUNCATED)
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PMID:Mitochondria and diabetes. Genetic, biochemical, and clinical implications of the cellular energy circuit. 854 53

Impairments in mitochondrial energy metabolism are thought to be involved in most neurodegenerative diseases, including Huntington's disease (HD). Chronic administration of 3-nitropropionic acid (3-NP), a suicide inhibitor of succinate dehydrogenase, causes prolonged energy impairments and replicates most of the pathophysiological features of HD, including preferential striatal degeneration. In this study, we analyzed one of the mechanisms that could account for this selective 3-NP-induced striatal degeneration. In chronically 3-NP-infused rats, the time course of motor behavioral impairments and histological abnormalities was determined. Progressive alterations of motor performance occurred after 3 d. By histological analysis and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end-labeling staining, we found a selective neurodegenerescence in the striatum, occurring first in its dorsolateral (DL) part. Activation of c-Jun N-terminal kinase (JNK) was analyzed from brain sections of these rats, using immunocytochemical detection of its phosphorylated form. Activation of JNK occurred progressively and selectively in the DL of the striatum and was followed by c-Jun activation and expression in the same striatal region. To elucidate the role of the JNK/c-Jun module in 3-NP-induced striatal degeneration, we then used primary striatal neurons in culture, in which we replicated neuronal death by application of 3-NP. We found strong nuclear translocation of activated JNK that was rapidly followed by phosphorylation of the transcription factor c-Jun. Overexpression of a dominant negative version of c-Jun, lacking its transactivation domain and phosphorylation sites for activated JNK, completely abolished 3-NP-induced striatal neurodegeneration. We thus conclude that a genetic program controlled by the JNK/c-Jun module is an important molecular event in 3-NP-induced striatal degeneration.
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PMID:The mitochondrial toxin 3-nitropropionic acid induces striatal neurodegeneration via a c-Jun N-terminal kinase/c-Jun module. 1189 57