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

---

Query: EC:1.6.5.3 (complex I)
8,901 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The electron transfer complexes, succinate: ubiquinone reductase, ubiquinone: cytochrome c reductase, and cytochrome c: O2 oxidase were isolated from the mitochondrial membranes of Neurospora crassa by the following steps. Modification of the contents of the complexes in mitochondria by growing cells on chloramphenicol; solubilisation of the complexes by Triton X-100; affinity chromatography on immobilized cytochrome c and ion exchange and gel chromatography. Ubiquinone reductase was obtained in a monomeric form (Mr approximately 130 000) consisting of a flavin subunit (Mr 72 000) an iron-sulfur subunit (Mr 28 000) and a cytochrome b subunit (Mr probably 14 000). Cytochrome c reductase was obtained in a dimeric form (Mr approximately 550 000), the monomeric unit comprising the cytochromes b (Mr each 30 000), a cytochrome c1 (Mr 31 000), the iron-sulfur subunit (Mr 25 000), and six subunits without known prosthetic groups (Mr 9000, 11 000, 14 000, 45 000, 45 000, and 52 000). Cytochrome c oxidase was also isolated in a dimeric form (Mr approximately 320 000) comprising two copies each of seven subunits (Mr 9000, 12 000, 14 000, 18 000, 21 000, 29 000, and 40 000). The complexes were essentially free of phospholipid. Each bound one micelle of Triton X-100 (Mr approximately 90 000). After isolation, the bound Triton X-100 could be replaced by other nonionic detergents such as: alkylphenyl polyoxyethylene ethers, alkyl polyoxyethylene ethers and acyl polyoxyethylene sorbitan esters.
...
PMID:Isolation of mitochondrial succinate: ubiquinone reductase, cytochrome c reductase and cytochrome c oxidase from Neurospora crassa using nonionic detergent. 22 65

Bovine mitochondrial NADH-ubiquinone reductase (complex I), the first enzyme in the electron-transport chain, is a membrane-bound assembly of more than 30 different proteins, and the flavoprotein (FP) fraction, a water-soluble assembly of the 51-, 24-, and 10-kDa subunits, retains some of the catalytic properties of the enzyme. The 51-kDa subunit binds the substrate NAD(H) and probably contains both the cofactor, FMN, and also a tetranuclear iron-sulfur center, while a binuclear iron-sulfur center is located in the 24- or 10-kDa proteins. The 75-kDa subunit is the largest of the six proteins in the iron-sulfur protein (IP) fraction, and its sequence indicates that it too contains iron-sulfur clusters. Partial protein sequences have been determined at the N-terminus and at internal sites in the 51-kDa subunit, and the corresponding cDNA encoding a precursor of the protein has been isolated by using a novel strategy based on the polymerase chain reaction. The mature protein is 444 amino acids long. Its sequence, and those of the 24- and 75-kDa subunits, shows that mitochondrial complex I is related to a soluble NAD-reducing hydrogenase from the facultative chemolithotroph Alcaligenes eutrophus H16. This enzyme has four subunits, alpha, beta, gamma, and delta, and the alpha gamma dimer is an NADH oxidoreductase that contains FMN. The gamma-subunit is related to residues 1-240 of the 75-kDa subunit of complex I, and the alpha-subunit sequence is a fusion of homologues of the 24- and 51-kDa subunits, in the order N- to C-terminal. The most highly conserved regions are in the 51-kDa subunit and probably form parts of nucleotide binding sites for NAD(H) and FMN. Another conserved region surrounds the sequence motif CysXXCysXXCys, which is likely to provide three of the four ligands of a 4Fe-4S center, possibly that known as N-3. Characteristic ligands for a second 4Fe-4S center are conserved in the 75-kDa and gamma-subunits. This relationship with the bacterial enzyme implies that the 24- and 51-kDa subunits, together with part of the 75-kDa subunit, constitute a structural unit in mitochondrial complex I that is concerned with the first steps of electron transport.
...
PMID:Relationship between mitochondrial NADH-ubiquinone reductase and a bacterial NAD-reducing hydrogenase. 190 Jan 94

Naturally occurring quinones and quinone-containing extracts of seeds of the toxic plant Cassia obtusifolia (sicklepod) affected muscle mitochondrial function. Aqueous suspensions and organic extracts of C. obtusifolia seeds slightly elevated plasma creatine kinase levels of Sprague-Dawley rats. These extracts were analyzed by fused silica capillary gas chromatography and found to contain nine anthraquinones and three anthrones. Urinary metabolites primarily consisted of beta-glucuronide conjugates of the anthraquinones. The three anthrones or conjugate analogues were not present in the urine in detectable amounts. Emodin, doxorubicin and organic extracts of C. obtusifolia inhibited NADH:cytochrome c oxidoreductase activity of bovine heart mitochondrial particles and NADH:CoQ oxidoreductase activity of porcine heart mitochondrial NADH dehydrogenase, whereas juglone was stimulatory. Relative quinone metabolism correlated with semiquinone formation rate and with redox potential. A protective effect of coenzyme Q against enzyme inhibition by anthraquinones was also observed.
...
PMID:Effects of Cassia obtusifolia (sicklepod) extracts and anthraquinones on muscle mitochondrial function. 274 52

Cardiac mitochondrial NADH dehydrogenase (Cytochrome c reductase, EC1.6.99.3) catalyses the reduction of ferricytochrome c to ferrocytochrome c by NADH. In the presence of the anthracycline anti-tumour drug, adriamycin, electron transfer from NADH is subverted to dioxygen. Using the electron spin resonance technique of spin trapping with the spin trapping agent 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) adriamycin was found to stimulate the formation of superoxide and hydroxyl radicals in the NADH/NADH dehydrogenase reaction. Hydroxyl radical formation is dependent on the availability of trace amounts of redox active metal ions - particularly ferric ions. Trace amounts of ferric ions catalyse the formation of hydroxyl radicals by both superoxide-dependent and adriamycin-dependent one electron reduction of hydrogen peroxide. The metabolism of adriamycin by cardiac mitochondrial NADH dehydrogenase may be an important etiological factor in adriamycin-induced cardiotoxicity. It may be therapeutically beneficial to keep nonessential ferric/ferrous ions in the myocardium at minimum levels with siderophoric iron chelators - providing the anti-tumour activity of adriamycin is not impaired.
...
PMID:Reduction of oxygen by NADH/NADH dehydrogenase in the presence of adriamycin. 285 Feb 70

A simple procedure for preparation of highly purified soluble succinate-ubiquinone reductase from bovine heart mitochondrial particles is described. The enzyme exhibits four major bands on sodium dodecyl sulfate gel electrophoresis and contains (nmol per mg protein): covalently bound flavin, 6; non-heme iron, 53; acid-labile sulfur, 50; cytochrome b-560 heme, 1.2. The enzyme catalyzes thenoyltrifluoroacetone, or carboxin-sensitive (pure non-competitive with Q2) reduction of Q2 by succinate with a turnover number close to that in parent submitochondrial particles. The succinate reduced enzyme exhibits ferredoxin-type iron-sulfur center EPR-signal (g = 1.94 species) and a semiquinone signal (g = 2.00). An oxidized preparation shows a symmetric signal centered around g = 2.01. An unusual dissociation of the enzyme in the absence of a detergent is described. When added to the assay mixture from a concentrated protein-detergent solution, the enzyme does not reduce Q2 being highly reactive towards ferricyanide ('low Km ferricyanide reactive site'; Vinogradov, A.D., Gavrikova, E.V. and Goloveshkina, V.G. (1975) Biochem. Biophys. Res. Commun. 65, 1264-1269). The ubiquinone reductase, not the ferricyanide reductase was observed when the enzyme was added to the assay mixture from the diluted protein-detergent solutions. Thus the dissociation of succinate dehydrogenase from the complex occurs in the absence of a detergent dependent on the concentration of the protein-detergent complex in the stock preparation where the samples for the assay are taken from. An active antimycin-sensitive succinate-cytochrome c reductase was reconstituted by admixing of the soluble succinate-ubiquinone reductase and the cytochrome b-c1 complex, i.e., from the complexes which both contain the ubiquinone reactivity conferring protein (QPs). Cytochrome c reductase was also reconstituted from the succinate-ubiquinone reductase and succinate-cytochrome c reductase containing inactivated succinate dehydrogenase. The reconstitution experiments suggest that there exists a specific protein-protein (or lipid) interaction between QPs and a certain component(s) of the b-c1 complex.
...
PMID:Studies on the succinate dehydrogenating system. Isolation and properties of the mitochondrial succinate-ubiquinone reductase. 299 19

The NADH and NADPH ferricyanide reductase activities present in mitochondrial NADH-CoQ reductase preparations have been studied utilizing two photoaffinity pyridine nucleotide analogues: arylazido-beta-alanyl NAD+ (A3'-O-[3-[N-(4-azido-2-nitrophenyl)amino]propionyl]NAD+) and arylazido-beta-alanyl NADP+ (N3'-O-[3-[N-(4-azido-3-nitrophenyl)amino]propionyl]NADP+). For the NADH-K3Fe(CN)6 reductase activity, arylazido-beta-alanyl NAD+ was found to be, in the dark, a competitive inhibitor with respect to both NADH and K3Fe(CN)6 with Ki,app values of 9.7 and 15.5 microM, respectively. In comparison the NADP+ analogue exhibited weak noncompetitive inhibitor activity for this reaction against both substrates. Upon photoirradiation arylazido-beta-alanyl NAD+ inhibited NADH-K3Fe(CN)6 reductase up to 70% in the presence of a 25-fold molar excess of analogue over the enzyme concentration. This photodependent inhibition could be prevented by the presence, during irradiation, of the natural substrate NADH. In contrast complex kinetic results were obtained with studies of the effects of the pyridine nucleotide analogues of NADPH-K3Fe(CN)6 reductase activity in the dark. Photoirradiation of either analogue in the presence of the enzyme complex resulted in an activation of NADPH-dependent activity. The possibility that the NADPH-K3Fe(CN)6 reductase activity of complex I represents a summation of the combined ferricyanide reductase activity of the NADPH-NAD+ transhydrogenase and NADH oxidoreductase is suggested.
...
PMID:Studies of the ferricyanide reductase activities of the mitochondrial reduced nicotinamide adenine dinucleotide-ubiquinone reductase (complex I) utilizing arylazido-beta-alanyl NAD+ and arylazido-beta-alanyl NADP+. 392 31

We studied two diagnostic aspects of fatal infantile defects of the mitochondrial respiratory chain: the age dependence of muscle mitochondrial enzyme activities and the reliability of diagnosis from autopsy samples. In morphologically normal quadriceps muscle samples of 46 children between the ages of 3 days and 15 years, activities of complex I plus III (NADH:cytochrome c oxidoreductase) and complex II plus III (succinate:cytochrome c oxidoreductase) increased 2-fold during the first three years of life, while that of complex II (succinate dehydrogenase), complex IV (cytochrome c oxidase), and citrate synthase did not show significant correlation with age. We suggest that these changes are related to age and stress the importance of strictly age-matched controls when diagnosing a mitochondrial disease of early childhood. The value of autopsy samples in diagnostic studies was evaluated by comparing mitochondrial enzyme activities in quadriceps muscle from autopsies and from surgical biopsies. In quadriceps muscle mitochondria, all the enzyme activities studied remained stable for at least 3 h after death. Using age-matched controls and autopsy samples, we diagnosed a respiratory chain enzyme deficiency in two infants, and the defects were confirmed in cultured skin fibroblasts.
...
PMID:Diagnosis of fatal infantile defects of the mitochondrial respiratory chain: age dependence and postmortem analysis of enzyme activities. 874 50

NADH-quinone oxidoreductase is classified into two groups, NADH dehydrogenase-1 (NDH-1) and NADH dehydrogenase-2 (NDH-2). Animal mitochondrial complex I is an NDH-1 type enzyme. Previously, we isolated potent inhibitors from plants to both NDH-1 and NDH-2. We have now examined detailed inhibitory effects of three tannins (pentagalloylglucose, sanguiin H-11, and oolonghomobisflavan A) on NDH-1 using bovine heart mitochondrial complex I and a subcomplex flavoprotein (containing 3 subunits) derived from complex I. Although many specific inhibitors of NDH-1 (e.g. rotenone and piericidin A) have been reported, the reactive sites are at or near to, the ubiquinone-binding site. NADH-ubiquinone-1 oxidoreductase activity of complex I was inhibited by the three tannins, among which sanguiin H-11 was the most potent inhibitor. NADH-menadione oxidoreductase activity of complex I was susceptible to the three tannins, but completely resistant to rotenone. The inhibitory effects of tannins were all noncompetitive with respect to NADH, ubiquinone-1, and menadione. The NADH-menadione oxidoreductase of flavoprotein was also inhibited by the three tannins, but not by rotenone, which is consistent with the fact that flavoprotein does not contain a native ubiquinone-binding site. The study of the NADH reduced-minus-oxidized difference spectrum of flavoprotein under steady-state conditions indicated that the inhibitory sites of sanguiin H-11 and oolonghomobisflavan A exist between the NADH binding site and the FMN site, and that for pentagalloylglucose exists between FMN and an artificial electron acceptor-binding site. These results suggest that the tannins are potent inhibitors of NADH dehydrogenases, and that the inhibitory mechanisms are novel.
...
PMID:Inhibitory effects of tannins on the NADH dehydrogenase activity of bovine heart mitochondrial complex I. 1022 Feb 77

Mitochondrial enzyme activities and ultrastructure of mitochondria prepared from klotho mutant mice were compared with those in wild-type mice. We also measured the levels of expression of ND1, 51kDa, and 75kDa mRNA associated with the genes encoding NADH dehydrogenase and complex I and that of alpha cardiac myosin heavy chain mRNA in both groups. Mitochondrial NADH oxidoreductase activity was higher in klotho mutant mice during aging than that in wild-type mice. The area of mitochondria per unit area (300 microm2) of cell was almost constant from 4 to 7 weeks of age in both groups. A few large mitochondria were scattered between numerous small mitochondria with compact cristae and myofibrils in klotho mice from 5 weeks of age. The levels of ND1 and 75kDa mRNA were slightly high from 7 weeks of age in klotho mutant mice, whereas they were almost constant in wild-type mice, in spite of reduced expression of alpha cardiac myosin heavy chain mRNA. Our results indicate that klotho protein indirectly plays a role in diminished functional adaptability of enzymes in aged heart muscle, and is required for hypertrophy of cardiac mitochondria.
...
PMID:NADH dehydrogenase activity and expression of mRNA of complex I (ND1, 51kDa, and 75kDa) in heart mitochondria of klotho mouse. 1621 76

Verticipyrone has recently been isolated from the culture broth of Verticillium sp. and shown to inhibit NADH fumarate reductase, as well as NADH oxidoreductase (complex I) of the mitochondrial electron transport chain. In order to assess the structural elements in verticipyrone essential for complex I inhibitor, 15 structural analogues were prepared and analyzed for their effects on mitochondrial NADH oxidoreductase and NADH oxidase activities. Also measured were the abilities of several of the analogues to inhibit respiration as judged by a shift to glycolysis, and to inhibit the growth of several mammalian cell lines. The nature of the pyrone ring was shown to be important to potency of inhibition, as was the length and nature of substituents in the side chain of the analogues.
...
PMID:Synthesis and evaluation of verticipyrone analogues as mitochondrial complex I inhibitors. 2045 60


1 2 Next >>

---