Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to investigate clinical, biochemical, and genetic features in 7 probands (a total of 11 patients) with nicotine-amide adenine dinucleotide (NADH) dehydrogenase (complex I) deficiency. We screened the mitochondrial DNA for mutations and found pathogenic mutations in complex I genes (mitochondrial NADH dehydrogenase subunit (MTND) genes) in three probands. The 10191T>C mutation in MTND3 and the 14487T>C mutation in MTND6 were present in two probands with Leigh's-like and Leigh's syndrome, respectively. Four siblings with a syndrome consisting of encephalomyopathy with hearing impairment, optic nerve atrophy, and cardiac involvement had the 11778G>A mutation in MTND4, previously associated with Leber hereditary optic neuropathy. These findings demonstrate that mutations in MTND genes are relatively frequent in patients with complex I deficiency. Biochemical measurements of respiratory chain function in muscle mitochondria showed that all patients had a moderate decrease of the mitochondrial adenosine triphosphate production rate. Interestingly, the complex I deficiency caused secondary metabolic alterations with decreased oxaloacetate-induced inhibition of succinate dehydrogenase (complex II) and excretion of Krebs cycle intermediates in the urine. Our results thus suggest that altered regulation of metabolism may play an important role in the pathogenesis of complex I deficiency.
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PMID:Secondary metabolic effects in complex I deficiency. 1604 24

Extracellular and intraneuronal formation of amyloid-beta (Abeta) deposits have been demonstrated to be involved in the pathogenesis of Alzheimer's disease (AD). However, the precise mechanism of Abeta neurotoxicity is not completely understood. Previous studies suggest that binding of Abeta with a number of targets have deleterious effects on cellular functions. It has been shown that Abeta directly interacted with intracellular protein ERAB (endoplasmic reticulum amyloid beta-peptide-binding protein) also known as ABAD (Abeta-binding alcohol dehydrogenase) resulting in mitochondrial dysfunction and cell death. In the present study we have identified another mitochondrial enzyme, ND3 of the human complex I, that binds to Abeta1-42 by the screening of a human brain cDNA library expressed on M13 phage. Our results indicated a strong interaction between Abeta and a phage-displayed 25 amino acid long peptide TTNLPLMVMSSLLLIIILALSLAYE corresponding to C-terminal peptide domain of NADH dehydrogenase, subunit 3 (MTND3) encoded by mitochondrial DNA (mtDNA). This interaction may explain, in part, the inhibition of complex I activity in astrocytes and neurons in the presence of Abeta, described recently. To our knowledge, the present study is the first demonstration of interaction between Abeta and one of the subunits of the human complex I.
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PMID:Identification of amyloid-beta 1-42 binding protein fragments by screening of a human brain cDNA library. 1638 38