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 studied the effect of riboflavin treatment on the clinical status and on the activities of beta-oxidation and respiratory chain enzymes in a 69-year-old patient with late-onset myopathy. Before treatment, she was very weak and wasted in the limbs and trunk muscles; also, she could not walk or attend to daily activities. Marked lipid storage was present in the muscle biopsy. The activities of short-chain acyl coenzyme A (acyl-CoA) dehydrogenase (SCAD), medium-chain acyl-CoA dehydrogenase (MCAD), and long-chain acyl-CoA dehydrogenase (LCAD) in isolated muscle mitochondria were reduced to less than 10% of control values. This defect in fatty acid oxidation was associated with a marked deficiency of two flavin-dependent respiratory chain complexes: complex I activity was 20% and complex II activity was 25% of control values. By contrast, the activities of the nonflavin-dependent complex III and complex IV were normal. Western blot analysis of the patient's muscle mitochondrial extracts with antibodies raised against purified SCAD, MCAD, and the alpha- and beta-subunits of the electron transfer flavoprotein (ETF) showed absence of SCAD cross-reacting material (CRM), markedly decreased MCAD-CRM, and normal amounts of both alpha- and beta-ETF-CRM. After riboflavin treatment, the patient's clinical status dramatically improved and morphologic changes in muscle disappeared. SCAD activity increased to 55% of control values, whereas MCAD, LCAD, and complex I and complex II activities normalized. SCAD and MCAD immunoreactivity was restored to normal. On the basis of our experience and the data in the literature, we concluded that some lipid storage myopathies can show dramatic response to riboflavin.
 ...
PMID:Late-onset riboflavin-responsive myopathy with combined multiple acyl coenzyme A dehydrogenase and respiratory chain deficiency. 796 76

The mitochondrial oxidative phosphorylation and fatty acid oxidation pathways have traditionally been considered independent major sources of cellular energy production; however, case reports of patients with specific enzymatic defects in either pathway have suggested the potential for a complex interference between the two. This study documents a new site of interference between the two pathways, a site in respiratory complex II capable of producing clinical signs of a block in fatty acid oxidation and reduced in vitro activity of acyl-CoA dehydrogenases. The initial patient, and later her newborn sibling, had mildly dysmorphic features, lactic acidosis and a defect in mitochondrial respiratory complex II associated with many biochemical features of a block in fatty acid oxidation. Results of in vitro probing of intact fibroblasts from both patients with methyl[2H3]palmitate and L-carnitine revealed greatly increased [2H3]butyrylcarnitine; however, the ratio of dehydrogenase activity with butyryl-CoA with anti-MCAD inactivating antibody (used to reveal SCAD-specific activity) to that with octanoyl-CoA was normal, excluding a selective SCAD or MCAD deficiency. Respiratory complex II was defective in both patients, with an absent thenoyltrifluoroacetone-sensitive succinate Q reductase activity that was partially restored by supplementation with duroquinone. Although secondary, the block in fatty acid oxidation was a major management problem since attempts to provide essential fatty acids precipitated acidotic decompensations. This study reinforces the need to pursue broadly the primary genetic defect within these two pathways, making full use of increasingly available functional and molecular diagnostic tools.
 ...
PMID:Respiratory complex II defect in siblings associated with a symptomatic secondary block in fatty acid oxidation. 1470 14