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

We describe two brothers, 25 and 19 years-old, with muscle pain and decreased strength after prolonged exercise; these symptoms are worsened by cold whether of fasting. One of the patients developed recurrent myoglobinuria and had one episode of renal failure. Laboratory investigations were normal between the crises, but during myoglobinuria, serum creatine kinase activity increased 100 times. Electromyography was suggestive of denervation. Muscle biopsy showed increased lipid droplets by the "oil red O" stain and increased activity of succinic dehydrogenase histochemical reaction. Lactate production during ischemia was normal. Biochemical analysis showed decreased carnitine-palmityl-transferase activity in muscle (7.23 and 10.58 nmoles/min/gr; normal range 66.7 +/- 17.3), with normal values for carnitine-octanoyl-transferase and carnitine-acetyl-transferase. The metabolic pathway of fatty acid utilization as an energy source for muscle during exercise in normal and in pathological conditions is discussed.
 ...
PMID:[Myopathy due to carnitine palmitoyltransferase deficiency. Report of 2 cases with enzymatic analyses on muscle tissue]. 666 Nov 2

We report on a 33-yr-old female patient with myalgia, CK values up to 3500 Ul-1 and proximal weakness. An initial muscle biopsy showed myositis. One year later an enlarged lymph node was investigated and sarcoidosis diagnosed. In a second muscle biopsy inflammatory cells and morphological characteristics of mitochondrial myopathy were found. Biochemical analyses indicated a 50% reduction in complex II activity of the respiratory chain. Due to failure in clinical improvement a third muscle biopsy was performed in 1990 where only 19% of normal complex II activity was present. Southern blot analysis of the mitochondrial genome was normal. Thus for the first time we describe a patient with sarcoid myopathy and a complex II deficiency. Our interpretation is that a pre-existing complex II defect became clinically relevant because of additional sarcoid myopathy.
 ...
PMID:Sarcoid myopathy and mitochondrial respiratory chain defects: clinicopathological, biochemical and molecular biological analyses. 758 Feb 39

Three patients with chronic progressive external ophthalmoplegia of adult-onset, generalized muscle atrophy and myalgia are described. Two patients fulfilled the histological criteria for centronuclear myopathy, the third those for fiber-type disproportion. Additionally, typical ragged red fibers were found in all muscle specimens, and several muscle fibers were cytochrome c oxidase negative. NADH and succinate dehydrogenase stains showed increased subsarcolemmal accumulation of mitochondria. To determine whether these findings are coincidental or whether they indicated an additional mitochondrial disorder, all patients were investigated using biochemical analysis of the respiratory chain, molecular genetics, magnetic resonance spectroscopy of quadriceps muscle and ergometry. These tests suggested an additional mitochondrial dysfunction. Mitochondrial dysfunction seems to be more common in this group of myopathies than previously estimated, and may be of importance in the pathogenesis of these disorders.
 ...
PMID:Mitochondrial dysfunction in adult-onset myopathies with structural abnormalities. 773 87

Skeletal muscle specimens from three patients with inclusion body myositis, aged 39, 60 and 71 years, respectively, were investigated. Enzyme histochemical staining of cytochrome c oxidase (COX), succinate dehydrogenase and myofibrillar ATPase, and in situ hybridization of transcripts of mitochondrial DNA (mtDNA) were performed on consecutive sections. In all three cases a proportion of muscle fibres (2-5%) showed low or absent COX activity in spite of medium or high succinate dehydrogenase activity (COX deficient muscle fibres). Two probes detecting transcripts of different segments of mtDNA were used for the in situ hybridization. One of the probes (ND4 probe) detected transcripts of a segment of the NADH dehydrogenase subunit 4 gene, which is known to be affected in most cases of mitochondrial myopathy with large deletions of mtDNA. There was reduced hybridization of the ND4 probe in many COX deficient muscle fibres compared with adjacent normal fibres. The other probe (ND2 probe) detected transcripts of a segment of the NADH dehydrogenase subunit 2 gene, which usually is not included in mtDNA deletions. There was accumulation of transcripts corresponding to the ND2 probe in COX deficient fibres in all three cases. These findings demonstrate that deleted mtDNA had accumulated in COX deficient muscle fibres in patients with inclusion body myositis. Southern blot analysis of mtDNA in muscle revealed a 16.6 kb fragment corresponding to normal mtDNA in all three cases. In one case two additional less abundant fragments of smaller size, corresponding to deleted mtDNA, were detected. Ultrastructural investigation showed abnormal mitochondria in all three cases. Control muscle specimens were obtained from nine patients, aged 63-71 years, with muscle pain but without morphological evidence of muscle disease. Occasional COX deficient fibres (< 1%) were found in three of the control cases. The other six control cases showed no COX deficient fibres. Our results show that mtDNA deletions may be involved in the pathogenesis of inclusion body myositis and cause respiratory chain dysfunction in muscle fibre segments.
 ...
PMID:Mitochondrial DNA deletions in inclusion body myositis. 838 16

Formoterol, a selective beta 2-adrenoceptor agonist, has been introduced recently in the treatment of poorly controlled asthma. A patient is presented who developed myalgia and muscle weakness, associated with an elevation of creatine kinase (CK) during treatment with formoterol. Subsequent muscle biopsy demonstrated atrophic fibres lacking cytochrome C-oxidase and succinate dehydrogenase, suggestive of mitochondrial dysfunction. There were no inflammatory changes. Immunocytochemical analysis using antibodies to alpha-actinin-2 and alpha-actinin-3 demonstrated positive staining of 'rod-like' bodies in atrophic fibres. Clinical and biochemical improvement occurred following withdrawal of formoterol. Possible mechanisms involved in the development of myopathy are explored.
 ...
PMID:Mitochondrial dysfunction and rod-like lesions associated with administration of beta2 adrenoceptor agonist formoterol. 1514 39

To investigate fibre-type abnormalities in women with work-related myalgia (WRM), tissue samples were extracted from their trapezius (TRAP) and the extensor carpi radialis brevis (ECRB) muscles and compared with healthy controls (CON). For the ECRB samples (CON, n = 6; WRM, n = 11), no differences (P > 0.05) were found between groups for any of the properties examined, namely fibre-type (I, IIA, IIX, IIAX) distribution, cross-sectional fibre area, capillary counts (CC), capillary to fibre area ratio, and succinic dehydrogenase activity. For the TRAP samples (CON, n = 6; WRM, n = 8), the only difference (P < 0.05) observed between groups was for CC (CON > WRM), which was not statistically significant (P > 0.05) when age was used a covariant. A comparison of the properties of these 2 muscles in the CON group indicated a higher (P < 0.05) and lower (P < 0.05) percentage of type I and type IIA fibres, respectively, in the TRAP as well as higher (P < 0.05) CC, which was not specific to fibre type. These preliminary results suggest that the properties employed to characterize fibre types do not differentiate CON from WRM for either the TRAP or ECRB. As a consequence, the role of inherent fibre-type differences between these muscles in the pathogenesis of WRM remains uncertain.
...
PMID:A pilot study to determine whether differences exist in histochemical properties between the trapezius and extensor carpi radialis brevis muscles in women with work-related myalgia. 2470 14

HDL and apolipoprotein A1 (apoA1) concentrations inversely correlate with risk of death from ischemic heart disease; however, the role of apoA1 in the myocardial response to ischemia has not been well defined. To test whether apoA1, the primary HDL apolipoprotein, has an acute anti-inflammatory role in ischemic heart disease, we induced myocardial infarction via direct left anterior descending coronary artery ligation in apoA1 null (apoA1(-/-)) and apoA1 heterozygous (apoA1(+/-)) mice. We observed that apoA1(+/-) and apoA1(-/-) mice had a 52% and 125% increase in infarct size as a percentage of area at risk, respectively, compared with wild-type (WT) C57BL/6 mice. Mitochondrial oxidation contributes to tissue damage in ischemia-reperfusion injury. A substantial defect was present at baseline in the electron transport chain of cardiac myocytes from apoA1(-/-) mice localized to the coenzyme Q (CoQ) pool with impaired electron transfer (67% decrease) from complex II to complex III. Administration of coenzyme Q10 (CoQ10) to apoA1 null mice normalized the cardiac mitochondrial CoQ pool and reduced infarct size to that observed in WT mice. CoQ10 administration did not significantly alter infarct size in WT mice. These data identify CoQ pool content leading to impaired mitochondrial function as major contributors to infarct size in the setting of low HDL/apoA1. These data suggest a previously unappreciated mechanism for myocardial stunning, cardiac dysfunction, and muscle pain associated with low HDL and low apoA1 concentrations that can be corrected by CoQ10 supplementation and suggest populations of patients that may benefit particularly from CoQ10 supplementation.
...
PMID:Apolipoprotein A1 regulates coenzyme Q10 absorption, mitochondrial function, and infarct size in a mouse model of myocardial infarction. 2475 32

Mitochondrial myopathy with episodic hyper-creatine kinase (CK)-emia (MIMECK) is a new disease entity characterized by episodic or persistent muscle weakness and elevated CK levels. We herein report two cases of MIMECK with the findings of histopathological studies. Histopathological examinations revealed strongly succinate dehydrogenase-reactive vessels. Electron microscopy showed abnormal mitochondria in the vessels and proliferating and vacuolated mitochondria under the sarcolemma. Both patients exhibited recurrent severe myalgia, weakness and increased CK levels. L-arginine treatment significantly ameliorated their muscle symptoms. These findings indicate that mitochondrial angiopathy plays an important role in the pathophysiology of MIMECK. L-arginine may be a potential therapeutic agent for this disorder.
...
PMID:Clinical and Electron Microscopic Findings in Two Patients with Mitochondrial Myopathy Associated with Episodic Hyper-creatine Kinase-emia. 2666 15

Defects in iron-sulphur [Fe-S] cluster biogenesis are increasingly recognized as causing neurological disease. Mutations in a number of genes that encode proteins involved in mitochondrial [Fe-S] protein assembly lead to complex neurological phenotypes. One class of proteins essential in the early cluster assembly are ferredoxins. FDX2 is ubiquitously expressed and is essential in the de novo formation of [2Fe-2S] clusters in humans. We describe and genetically define a novel complex neurological syndrome identified in two Brazilian families, with a novel homozygous mutation in FDX2. Patients were clinically evaluated, underwent MRI, nerve conduction studies, EMG and muscle biopsy. To define the genetic aetiology, a combination of homozygosity mapping and whole exome sequencing was performed. We identified six patients from two apparently unrelated families with autosomal recessive inheritance of a complex neurological phenotype involving optic atrophy and nystagmus developing by age 3, followed by myopathy and recurrent episodes of cramps, myalgia and muscle weakness in the first or second decade of life. Sensory-motor axonal neuropathy led to progressive distal weakness. MRI disclosed a reversible or partially reversible leukoencephalopathy. Muscle biopsy demonstrated an unusual pattern of regional succinate dehydrogenase and cytochrome c oxidase deficiency with iron accumulation. The phenotype was mapped in both families to the same homozygous missense mutation in FDX2 (c.431C > T, p.P144L). The deleterious effect of the mutation was validated by real-time reverse transcription polymerase chain reaction and western blot analysis, which demonstrated normal expression of FDX2 mRNA but severely reduced expression of FDX2 protein in muscle tissue. This study describes a novel complex neurological phenotype with unusual MRI and muscle biopsy features, conclusively mapped to a mutation in FDX2, which encodes a ubiquitously expressed mitochondrial ferredoxin essential for early [Fe-S] cluster biogenesis.
 ...
PMID:A novel complex neurological phenotype due to a homozygous mutation in FDX2. 3001 Jul 96