Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q16795 (ubiquinone)
 5,455 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Complete sequences of mitochondrial (mt) genomes of eight Japanese Black cattle were determined to investigate the relationships between mt deoxyribonucleic acid (DNA) displacement loop (D-loop) types and other mtDNA regions and to identify the variation in the coding region that may influence the economic traits. The survey of mitochondrial sequences in the encoding region revealed 14 substitutions including six antonymous substitutions and one in 16S ribosomal ribonucleic acid (rRNA). Three methods of polymorphic DNA analyses (polymerase chain reaction [PCR]-restriction fragment length polymorphism [RFLP], mismatch PCR-RFLP, PCR-single-strand conformation polymorphism [SSCP]) were performed on these seven candidate substitutions (base pair [bp] 2,232, 12,158, 12,908, 13,310, 14,122, 14,140, and 14,565) for 202 Japanese Black cattle. The substitution of bp 13,310 was observed in all samples, but not in the reference sequence, indicating that this is a minor substitution or a sequencing mistake in the reference sequence. The substitutions at bp 14,122, 14,140, and 14,565 were observed in only a few samples, suggesting that these were also minor substitutions. The substitutions at bp 2,232 (16S rRNA), 12,158, and 12,908 (reduced nicotinamide adenine dinucleotide-ubiquinone oxidoreductase chain-5) were closely related to mitochondrial D-loop types that have previously been related to differences in the carcass traits of Japanese Black cattle. Evaluation of the effects on six carcass traits with mixed model procedures suggests that the bp 2,232 substitution affects longissimus muscle area and beef marbling score. The substitution at bp 2,232 is a strong candidate for the mitochondrial effect on meat quality.
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PMID:Identification of mitochondrial DNA substitutions related to meat quality in Japanese Black cattle. 1259 74

There is considerable evidence suggesting that mitochondrial dysfunction and oxidative damage may play a role in the pathogenesis of Parkinson's disease (PD). This possibility has been strengthened by recent studies in animal models, which have shown that a selective inhibitor of complex I of the electron transport gene can produce an animal model that closely mimics both the biochemical and histopathological findings of PD. Several agents are available that can modulate cellular energy metabolism and that may exert antioxidative effects. There is substantial evidence that mitochondria are a major source of free radicals within the cell. These appear to be produced at both the iron-sulfur clusters of complex I as well as the ubiquinone site. Agents that have shown to be beneficial in animal models of PD include creatine, coenzyme Q(10), Ginkgo biloba, nicotinamide, and acetyl-L-carnitine. Creatine has been shown to be effective in several animal models of neurodegenerative diseases and currently is being evaluated in early stage trials in PD. Similarly, coenzyme Q(10) is also effective in animal models and has shown promising effects both in clinical trials of PD as well as in clinical trials in Huntington's disease and Friedreich's ataxia. Many other agents show good human tolerability. These agents therefore are promising candidates for further study as neuroprotective agents in PD.
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PMID:Bioenergetic approaches for neuroprotection in Parkinson's disease. 1266 97

The purpose of the current study was to investigate aspects of improved bioenergetic function using nicotinamide during stroke. Using a global ischemia-reperfusion mouse model, ATP was depleted by 50% in the brain. The use of nicotinamide to provide a large reserve of brain NAD+ restored ATP levels to 61% of control levels. Alternatively, using nicotinamide as a PARP inhibitor restored ATP levels up to 72%. However, using a large reserve of NAD+ in the brain together with PARP inhibition proved to be additive, restoring ATP to 85% of control levels during the first critical 5 min of reperfusion. NAD+ and ATP levels correlated almost exactly. Brain mitochondrial function was also examined after cerebral ischemia-reperfusion. State 3 respiration of complex I was found to be abolished. However, this was a non-permanent inhibition of activity in vitro, since (NADH ubiquinone oxideroductase) complex I activity in these mitochondria was restored upon the addition of NADH. In vivo, the use of increased brain NAD+ and PARP inhibition was able to partially restore mitochondrial respiration. Taken together, the results show that nicotinamide offers a substantial protective role in terms of preservation of cellular ATP and mitochondrial NAD-linked respiration.
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PMID:Nicotinamide offers multiple protective mechanisms in stroke as a precursor for NAD+, as a PARP inhibitor and by partial restoration of mitochondrial function. 1451 2

We report the complete sequence of the mitochondrial genome of Penicillium marneffei, the first complete mitochondrial DNA sequence of a thermal dimorphic fungus. This 35 kb mitochondrial genome contains the genes encoding ATP synthase subunits 6, 8, and 9 (atp6, atp8, and atp9), cytochrome oxidase subunits I, II, and III (cox1, cox2, and cox3), apocytochrome b (cob), reduced nicotinamide adenine dinucleotide ubiquinone oxireductase subunits (nad1, nad2, nad3, nad4, nad4L, nad5, and nad6), ribosomal protein of the small ribosomal subunit (rps), 28 tRNAs, and small and large ribosomal RNAs. Analysis of gene contents, gene orders, and gene sequences revealed that the mitochondrial genome of P. marneffei is more closely related to those of molds than yeasts.
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PMID:The mitochondrial genome of the thermal dimorphic fungus Penicillium marneffei is more closely related to those of molds than yeasts. 1467 58

The mechanism of the energy-converting NADH (beta-nicotinamide adenine dinucleotide, reduced form):ubiquinone oxidoreductase, which is also called respiratory complex I, is largely unknown due to lack of a high-resolution structure and the most complicated construction of the enzyme. Electron transport is carried out by one flavin mononucleotide (FMN) and up to 9 Fe/S clusters. The Fe/S cluster N2, which is believed to be directly involved in redox-coupled proton-translocation, is located on subunit NuoB (the homologue of the mitochondrial PSST subunit). This subunit contains a conserved binding motif for a [4Fe/4S] cluster with two adjacent cysteines. It was questioned whether these adjacent cysteines could be ligands of the same cluster due to a possible steric hinderance. However, mutagenesis of either of these cysteines led to a loss of cluster N2. We used the known structure of the homologous small subunit of hydrogenases containing a regular cysteine motif to generate an in silico mutant with two consecutive cysteines. Molecular dynamics simulation showed that the conformation of these cysteines does not meet the topological requirements for coordination of a [4Fe/4S] cluster when the protein backbone conformation is kept constant. In comparison, the simulation of a dipeptide amide using a "template forcing" approach resulted in a conformation compatible to an optimal coordination of the two cluster positions in question. Thus, a slight main-chain conformational change would allow two adjacent cysteines to coordinate a [4Fe/4S] cluster.
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PMID:Adjacent cysteines are capable of ligating the same tetranuclear iron-sulfur cluster. 1522 87

Diabetes mellitus is associated with an increased production of reactive oxygen species and a reduction in antioxidant defenses. This leads to oxidative stress, which is partly responsible for diabetic complications. Tight glycemic control is the most effective way of preventing or decreasing these complications. Nevertheless, antioxidant micronutrients can be proposed as adjunctive therapy in patients with diabetes. Indeed, some minerals and vitamins are able to indirectly participate in the reduction of oxidative stress in diabetic patients by improving glycemic control and/or are able to exert antioxidant activity. This article reviews the use of minerals (vanadium, chromium, magnesium, zinc, selenium, copper) and vitamins or cofactors (tocopherol [vitamin E], ascorbic acid [vitamin C], ubidecarenone [ubiquinone; coenzyme Q], nicotinamide, riboflavin, thioctic acid [lipoic acid], flavonoids) in diabetes, with a particular focus on the prevention of diabetic complications. Results show that dietary supplementation with micronutrients may be a complement to classical therapies for preventing and treating diabetic complications. Supplementation is expected to be more effective when a deficiency in these micronutrients exists. Nevertheless, many clinical studies have reported beneficial effects in individuals without deficiencies, although several of these studies were short term and had small sample sizes. However, a randomized, double-blind, placebo-controlled, multicenter trial showed that thioctic acid at an oral dosage of 800 mg/day for 4 months significantly improved cardiac autonomic neuropathy in type 2 diabetic patients. Above all, individuals with diabetes should be educated about the importance of consuming adequate amounts of vitamins and minerals from natural food sources, within the constraints of recommended sugar and carbohydrate intake.
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PMID:The role of antioxidant micronutrients in the prevention of diabetic complications. 1574 12

Although the exact mechanism involved in the long-term depletion of brain serotonin (5-HT) produced by substituted amphetamines is not completely known, evidence suggests that oxidative and/or bioenergetic stress may contribute to 3,4-methylenedioxymethamphetamine (MDMA)-induced 5-HT toxicity. In the present study, the effect of supplementing energy substrates was examined on the long-term depletion of striatal 5-HT and dopamine produced by the local perfusion of MDMA (100 microM) and malonate (100 mM) and the depletion of striatal and hippocampal 5-HT concentrations produced by the systemic administration of MDMA (10 mg/kg i.p. x4). The effect of systemic administration of MDMA on ATP levels in the striatum and hippocampus also was examined. Reverse dialysis of MDMA and malonate directly into the striatum resulted in a 55-70% reduction in striatal concentrations of 5-HT and dopamine, and these reductions were significantly attenuated when MDMA and malonate were co-perfused with nicotinamide (1 mM). Perfusion of nicotinamide or ubiquinone (100 microM) also attenuated the depletion of 5-HT in the striatum and hippocampus produced by the systemic administration of MDMA. Finally, the systemic administration of MDMA produced a 30% decrease in the concentration of ATP in the striatum and hippocampus. These results support the conclusion that MDMA produces a dysregulation of energy metabolism which contributes to the mechanism of MDMA-induced 5-HT neurotoxicity.
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PMID:Evidence for a role of energy dysregulation in the MDMA-induced depletion of brain 5-HT. 1609 55

Degenerative brain disorders (neurodegeneration) can be frustrating for both conventional and alternative practitioners. A more comprehensive, integrative approach is urgently needed. One emerging focus for intervention is brain energetics. Specifically, mitochondrial insufficiency contributes to the etiopathology of many such disorders. Electron leakages inherent to mitochondrial energetics generate reactive oxygen free radical species that may place the ultimate limit on lifespan. Exogenous toxins, such as mercury and other environmental contaminants, exacerbate mitochondrial electron leakage, hastening their demise and that of their host cells. Studies of the brain in Alzheimer's and other dementias, Down syndrome, stroke, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, Friedreich's ataxia, aging, and constitutive disorders demonstrate impairments of the mitochondrial citric acid cycle and oxidative phosphorylation (OXPHOS) enzymes. Imaging or metabolic assays frequently reveal energetic insufficiency and depleted energy reserve in brain tissue in situ. Orthomolecular nutrients involved in mitochondrial metabolism provide clinical benefit. Among these are the essential minerals and the B vitamin group; vitamins E and K; and the antioxidant and energetic cofactors alpha-lipoic acid (ALA), ubiquinone (coenzyme Q10; CoQ10), and nicotinamide adenine dinucleotide, reduced (NADH). Recent advances in the area of stem cells and growth factors encourage optimism regarding brain regeneration. The trophic nutrients acetyl L-carnitine (ALCAR), glycerophosphocholine (GPC), and phosphatidylserine (PS) provide mitochondrial support and conserve growth factor receptors; all three improved cognition in double-blind trials. The omega-3 fatty acid docosahexaenoic acid (DHA) is enzymatically combined with GPC and PS to form membrane phospholipids for nerve cell expansion. Practical recommendations are presented for integrating these safe and well-tolerated orthomolecular nutrients into a comprehensive dietary supplementation program for brain vitality and productive lifespan.
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PMID:Neurodegeneration from mitochondrial insufficiency: nutrients, stem cells, growth factors, and prospects for brain rebuilding using integrative management. 1636 37

We report here the complete nucleotide sequence of the 30.9-kb mitochondrial genome of the dermatophyte fungus Epidermophyton floccosum. All genes are encoded on the same DNA strand and include seven subunits of the reduced nicotinamide adenine dinucleotide ubiquinone oxireductase (nad1, nad2, nad3, nad4, nad4L, nad5, and nad6), three subunits of cytochrome oxidase (cox1, cox2, and cox3), apocytochrome b (cob), three subunits of ATP synthase (atp6, atp8, and atp9), the small and large ribosomal RNAs (rns and rnl), and 25 tRNAs. A ribosomal protein gene (rps5) is present as an intronic ORF in the large ribosomal subunit. The genes coding for cob and cox1 carry one intron and nad5 carries two introns with ORFs. The mtDNA of E. floccosum has the same gene order as Trichophyton rubrum mtDNA, with the exception of some tRNA genes. Maximum likelihood phylogenetic analysis confirms T. rubrum as a close relative of E. floccosum. This is the first complete mitochondrial sequence of a species of the order Onygenales. This sequence is available under GenBank accession number AY916130.
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PMID:The complete DNA sequence of the mitochondrial genome of the dermatophyte fungus Epidermophyton floccosum. 1645 Jan 11

Addition of 90 micromolar reduced nicotinamide adenine dinucleotide (NADH) in the presence of cyanide to a suspension of aerobic mung bean (Phaseolus aureus) mitochondria depleted with ADP and uncoupler gives a cycle of reduction of electron transport carriers followed by reoxidation, as NADH is oxidized to NAD(+) through the cyanide-insensitive, alternate oxidase by excess oxygen in the reaction medium. Under these conditions, cytochrome b(553) and the nonfluorescent, high potential flavoprotein Fp(ha) of the plant respiratory chain become completely reduced with half-times of 2.5 to 2.8 seconds for both components. Reoxidation of flavoprotein Fp(ha) on exhaustion of NADH is more rapid than that of cytochrome b(553). There is a lag of 1.5 seconds after NADH addition before any reduction of ubiquinone can be observed, whereas there is no lag perceptible in the reduction of flavoprotein Fp(ha) and cytochrome b(553). The half-time for ubiquinone reduction is 4.5 seconds, and the extent of reduction is 90% or greater. About 30% of cytochrome b(557) is reduced under these conditions with a half-time of 10 seconds; both cytochrome b(562) and the fluorescent, high potential flavoprotein Fp(hf) show little, if any, reduction. The two cytochromes c in these mitochondria, c(547) and c(549), are reduced in synchrony with a half-time of 0.8 second. These two components are already 60% reduced in the presence of cyanide but absence of substrate, and they become completely reduced on addition of NADH. These results indicated that reducing equivalents enter the respiratory chain from exogenous NADH at flavoprotein Fp(ha) and are rapidly transported through cytochrome b(553) to the cytochromes c; once the latter are completely reduced, reduction of ubiquinone begins. Ubiquinone appears to act as a storage pool for reducing equivalents entering the respiratory chain on the substrate side of coupling site 2. It is suggested that flavoprotein Fp(ha) and cytochrome b(553) together may act as the branching point in the plant respiratory chain from which forward electron transport can take place to oxygen through the cytochrome chain via cytochrome oxidase, or to oxygen through the alternate, cyanide-insensitive oxidase via the fluorescent, high potential flavoprotein Fp(hf).
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PMID:The Respiratory Chain of Plant Mitochondria: VIII. Reduction Kinetics of the Respiratory Chain Carriers of Mung Bean Mitochondria with Reduced Nicotinamide Adenine Dinucleotide. 1665 17


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