Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Brain mitochondrial enzyme activities were examined in 15-day-old suckling mice which were daily injected with D-penicillamine (DP), a chelating agent of copper. Newborn mice treated with DP (1 g/kg/day) showed retarded weight gain, hyperelasticity of skin, and a bizarre forelimb posture with subcutaneous edema on experimental day (ED) 7. Paraparesis or dragging of the hindlimbs was observed by ED 15. Brain copper contents of DP-treated mice decreased to 34% of the controls of ED 15. Cytochrome c oxidase activity (complex IV) in the brain showed 51% decrease of the controls, on the contrary, rotenone-sensitive NADH cytochrome c reductase (complex I + III) and succinate cytochrome c reductase (complex II + III) were normal. Histochemistry of cytochrome c oxidase in the cerebellum of DP-treated mice disclosed diffuse reduction of staining, especially in Purkinje cells. These data show that DP-induced copper deficiency in the brain subsequently disturbs mitochondrial electron transport system, selectively cytochrome c oxidase activity. This seems to be a useful animal model not only for Menkes' kinky hair disease but also for mitochondrial encephalomyopathy.
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PMID:D-penicillamine-induced copper deficiency in suckling mice: neurological abnormalities and brain mitochondrial enzyme activities. 217 57

We report the clinical and autopsy findings in a young man of 18 with a chronic progressive disorder comprised of lactic acidosis, mental deterioration, and epileptic seizures which were sometimes accompanied by stroke-like episodes with transient hemiparesis and cortical blindness. He died of congestive heart failure. The autopsy showed lesions of the gray matter of the brain. Both the putamen and parieto-occipital cortex showed loss of neurons and proliferation of macrophages, astrocytes and vessels. There was marked loss of neurons in the inferior olives, and slight reduction of the number of Purkinje cells. Skeletal muscle studies revealed ragged-red fibers and structurally abnormal mitochondria. The heart was enlarged: accumulations of mitochondria occurred in the muscle fibers. The liver exhibited marked fatty degeneration. Biochemical analyses showed normal activities of pyruvate dehydrogenase in thrombocytes, pyruvate carboxylase in lymphocytes, biotinidase in serum as well as succinate dehydrogenase and cytochrome c oxidase. The features of this disorder differ in many respects from cases of mitochondrial encephalomyopathy previously reported and cannot be assigned to any specific disease entity.
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PMID:Mitochondrial encephalomyopathy. A variant with heart failure and liver steatosis. 367 21

A 16-year-old boy with mitochondrial encephalomyopathy had seizures, short stature, muscle weakness, progressive hearing loss, mental retardation, and myoclonus. His cranial computed tomography showed progressive calcification in the basal ganglia and cerebral atrophy. Muscle biopsy revealed many ragged-red fibers with variable cytochrome c oxidase activity and some strongly succinate dehydrogenase-reactive blood vessels. Sequence analysis of the entire mitochondrial DNA revealed a novel point mutation in the tRNA-Thr gene at nucleotide pair 15915. Serum lactate levels were decreased by high-dose coenzyme Q10 (CoQ10) therapy. The spectral power density, a parameter of background activity on electroencephalography, was markedly improved after additional administration of idebenone. After initiation of combined CoQ10 and idebenone therapy, the clinical abnormalities did not progress for 16 months.
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PMID:Mitochondrial encephalomyopathy with 15915 mutation: clinical report. 936 99

A 40-year-old woman who developed intestinal dysmobility was found, at rectal biopsy, to have marked microvacuolation of mucosal muscle layer cells, which corresponded to increased accumulation of abnormal mitochondria. Skeletal muscle biopsy specimens showed ragged-red fibers, vessels strongly reactive for succinic dehydrogenase, and focal deficiency of cytochrome c oxidase. Autopsy performed at the age of 50 revealed prominent accumulation of abnormal mitochondria in the intestinal smooth muscle cells with a mottled distribution of focal necrosis, multiple small cerebral infarcts with diffuse neuronal loss, and rarefaction of the perivascular white matter. Mitochondrial DNA analysis showed a point mutation at position 3243. This case, showing features of both mitochondrial neurogastrointestinal encephalomyopathy and mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), indicates that routine intestinal biopsy can detect mitochondrial encephalomyopathy with gastrointestinal involvement. The main intestinal changes were extensive accumulation of abnormal mitochondria in the leiomyocytes and scattered focal necrosis.
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PMID:Mitochondrial encephalomyopathy showing prominent microvacuolation and necrosis of intestinal smooth muscle cells: a case diagnosed by rectal biopsy. 967 17

We report a 15-year-old boy who presented with recurrent headaches associated with numbness, confusion, and speech difficulty. Brain magnetic resonance imaging (MRI) revealed diffuse bilateral white-matter hyperintensity on fluid-attenuated inversion-recovery and T2-weighted images in the internal capsule, periventricular and subcortical white matter, base of the pons, and middle cerebellar peduncles. Lesions were isointense on T1-weighted images and nonenhancing. Muscle biopsy showed changes consistent with a mitochondrial myopathy. Mitochondrial respiratory chain enzyme activity analysis revealed a significant reduction in complex II activity. Genetic testing was negative. We conclude that mitochondrial encephalomyopathy may present with unusual diffuse supratentorial and infratentorial white-matter changes on MRI.
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PMID:Diffuse magnetic resonance imaging white-matter changes in a 15-year-old boy with mitochondrial encephalomyopathy. 1191 71

A deficiency of succinate dehydrogenase is a rare cause of mitochondrial encephalomyopathy. Three patients, 2 sisters and 1 boy from an unrelated family, presented with symptoms and magnetic resonance imaging signs of leukoencephalopathy. Localized proton magnetic resonance spectroscopy indicated a prominent singlet at 2.40ppm in cerebral and cerebellar white matter not present in gray matter or basal ganglia. The signal was also elevated in cerebrospinal fluid and could be identified as originating from the two equivalent methylene groups of succinate. Subsequently, an isolated deficiency of complex II (succinate:ubiquinone oxidoreductase) was demonstrated in 2 patients in muscle and fibroblasts. One of the sisters died at the age of 18 months. Postmortem examination showed the neuropathological characteristics of Leigh syndrome. Her younger sister, now 12 months old, is also severely affected; the boy, now 6 years old, follows a milder, fluctuating clinical course. Magnetic resonance spectroscopy provides a characteristic pattern in succinate dehydrogenase deficiency.
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PMID:Succinate in dystrophic white matter: a proton magnetic resonance spectroscopy finding characteristic for complex II deficiency. 1211 45

'Myofibrillar myopathy' defines a myopathic condition with focal myofibrillar destruction and accumulation of degraded myofibrillar elements. Despite the fact that a number of mutations in different genes as well as cytotoxic agents lead to the disease, abnormal accumulation of desmin is a typical, common feature. Pathological changes of mitochondrial morphology and function have been observed in animal models with intermediate filament pathology. Therefore, in the present study we tested for mitochondrial pathology in skeletal muscle of five patients with the pathohistological diagnosis of myofibrillar myopathy. Screening for large-scale mtDNA deletions and the frequent MERRF (myoclonic epilepsy; ragged red fibres) and MELAS (mitochondrial encephalomyopathy; lactic acidosis; stroke) point mutations was negative in all patients. Histologically, all muscle biopsies showed nonspecific abnormalities of the oxidative/mitochondrial enzyme stainings (histochemistry for reduced nicotinamide adenine dinucleotide, succinic dehydrogenase, cytochrome c oxidase), only one of them had ragged red fibres and a significant number of cytochrome c oxidase-negative fibres. Upon biochemical investigation, four of our patients showed pathologically low respiratory chain complex I activities. Only one of our patients had a pathologically low complex IV activity, while the measurements of the others were within low normal range. The single patient with pathological values for both complex I and IV was the one with the clear histological hallmarks (ragged red and cytochrome c oxidase-negative fibres) of mitochondrial pathology. She also was the only patient with clinical signs hinting at a mitochondrial disorder. Together with data from observations in desmin- and plectin-deficient mice, our results support the view that desmin intermediate filament pathology in these cases is closely linked to mitochondrial dysfunction in skeletal muscle.
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PMID:Mitochondrial dysfunction in myofibrillar myopathy. 1258 39

Humanin (HN) was originally identified as an endogenous peptide that protects neuronal cells from apoptosis induced by various types of Alzheimer's disease-related insults. We have previously indicated that HN increases cellular ATP levels and speculated that this peptide may rescue energy-deficient cells in mitochondrial disorders. Here, we report, for the first time, increased HN expression in skeletal muscles from patients with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS). HN was strongly positive in all ragged-red fibers (RRFs) and some non-RRFs, and most of them were type 1 fibers generally requiring higher energy than type 2 fibers. HN in these fibers was localized in mitochondria. HN expression was also increased in small arteries that strongly reacted for succinate dehydrogenase. Our experiments on muscular TE671 cells indicated the possibility that synthesized HN increases cellular ATP levels by directly acting on mitochondria. From these in vivo and in vitro findings, we propose that HN expression might be induced in response to the energy crisis within affected fibers and vessels in MELAS muscles and further be a possible therapeutic candidate for MELAS.
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PMID:Humanin detected in skeletal muscles of MELAS patients: a possible new therapeutic agent. 1575 34

Numerous mitochondrial DNA mutations cause mitochondrial encephalomyopathy: a collection of related diseases for which there exists no effective treatment. Mitochondrial encephalomyopathies are complex multisystem diseases that exhibit a relentless progression of severity, making them both difficult to treat and study. The pathogenic and compensatory metabolic changes that are associated with chronic mitochondrial dysfunction are not well understood. The Drosophila ATP6(1) mutant models human mitochondrial encephalomyopathy and allows the study of metabolic changes and compensation that occur throughout the lifetime of an affected animal. ATP6(1)animals have a nearly complete loss of ATP synthase activity and an acute bioenergetic deficit when they are asymptomatic, but surprisingly we discovered no chronic bioenergetic deficit in these animals during their symptomatic period. Our data demonstrate dynamic metabolic compensatory mechanisms that sustain normal energy availability and activity despite chronic mitochondrial complex V dysfunction resulting from an endogenous mutation in the mitochondrial DNA. ATP6(1)animals compensate for their loss of oxidative phosphorylation through increases in glycolytic flux, ketogenesis and Kreb's cycle activity early during pathogenesis. However, succinate dehydrogenase activity is reduced and mitochondrial supercomplex formation is severely disrupted contributing to the pathogenesis seen in ATP6(1) animals. These studies demonstrate the dynamic nature of metabolic compensatory mechanisms and emphasize the need for time course studies in tractable animal systems to elucidate disease pathogenesis and novel therapeutic avenues.
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PMID:Modes of metabolic compensation during mitochondrial disease using the Drosophila model of ATP6 dysfunction. 2199 65

Mitochondrial disease is a group of rare disorders, caused by mitochondrial dysfunction. They are usually the result of mutations of either mitochondrial DNA or nuclear DNA. A3243G transition in the tRNALeu is one the most frequent mutations of the mitochondrial DNA. Phenotypic expression of this mutation varies. The most well-recognized phenotype is Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. Isolated myopathy with respiratory muscle weakness in this mutation has been rarely documented. The authors reported a 20-year-old Asian female presenting with a fulminant hypoventilatory respiratory failure with mild weakness of the limbs. Electrophysiologic study showed evidences of myopathy. Restrictive physiology of the lungs was demonstrated by pulmonary function test. Subsarcolemmal accumulation of mitochondria was demonstrated by Gomori trichrome and succinate dehydrogenase stains. Genetic study revealed the A3243G mutation in mitochondrial DNA in peripheral blood Isolated mitochondrial myopathy severely affecting respiratory muscles may be considered as an uncommon clinical spectrum of A3243G mitochondrial disease.
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PMID:Fulminant respiratory muscle paralysis, an expanding clinical spectrum of mitochondrial A3243G tRNALeu mutation. 2496 90


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