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)

The respiratory components of tightly coupled mitochondria from the filamentous fungus Aspergillus niger were studied. Cytochromes a + a(3), b, and c + c(1) were identified by difference spectra. The cytochrome spectra were qualitatively similar to yeast and rat liver mitochondria. The mitochondria contained, per gram of protein, an average of 2.9 and 7.0 mumoles of ubiquinone and nicotinamide adenine dinucleotide, respectively.
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PMID:Respiratory components of Aspergillus niger mitochondria. 430 98

Extraction with pentane virtually abolished reduced nicotinamide adenine dinucleotide oxidase activity in small particles from Azotobacter vinelandii, but activity was largely restored by added ubiquinone.
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PMID:Restoration by ubiquinone of Azotobacter vinelandii reduced nicotinamide adenine dinucleotide oxidase activity. 430 80

A ubiquinone-deficient mutant of Escherichia coli K-12 forming 20% of the normal amount of ubiquinone was compared with a normal strain. This lowered concentration of ubiquinone is still four times the concentration of cytochrome b(1). The mutant strain grew more slowly than the normal strain on a minimal medium with glucose as sole source of carbon and gave a lower aerobic growth yield than the normal strain. The reduced nicotinamide adenine dinucleotide (NADH) oxidase rate in membranes from the mutant strain was 40% of the oxidase rate in membranes from the normal strain, and the percentage reduction of cytochrome b(1) in the aerobic steady state, with NADH as substrate, was increased in membranes from the mutant strain. It is concluded that ubiquinone is required for maximum oxidase activity at the relatively high concentration (27 times that of cytochrome b(1)) found in normal cells. The results are discussed in relation to a scheme previously advanced for ubiquinone function in E. coli.
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PMID:Function of ubiquinone in Escherichia coli: a mutant strain forming a low level of ubiquinone. 433 83

A gentamicin-resistant mutant of Pseudomonas aeruginosa PAO503 was selected after ethyl methane sulfonate mutagenesis. The strain, P. aeruginosa PAO2401 had increased resistance to all aminoglycosides tested but exhibited no change for other antibiotics. The mutation designated aglA (aminoglycoside resistance) was 50% cotransducible with the 8-min ilvB,C marker on the P. aeruginosa chromosome. It showed a marked reduction in cytochrome c(552) and nitrate reductase (Nar) and a change in terminal oxidase activity. Cytochrome c(552) is a component of the P. aeruginosa Nar. No changes in succinate and reduced nicotinamide adenine dinucleotide dehydrogenases, ubiquinone content, Mg(2+)/Ca(2+) membrane adenosine triphosphatase, and energy coupling of electron transport to adenosine 5'-triphosphate synthesis were detected. Transport of gentamicin and dihydrostreptomycin was impaired in PAO2401, but transport of proline, arginine, glutamine, glucose or the polyamine spermidine was not reduced. Ribosomes of PAO2401, and PAO503 bound dihydrostreptomycin equally well, and cell extracts did not inactivate gentamicin or dihydrostreptomycin. Strain PAO2401 is resistant to gentamicin and dihydrostreptomycin because of impaired transport of these compounds. The transport studies indicate a selective coupling of dihydrostreptomycin and gentamicin transport with terminal electron transport. This conclusion was supported by results from another mutant (PAO417-T2) with increased Nar activity, enhanced dihydrostreptomycin and gentamicin transport and a reduction in resistance to these drugs. These results are discussed in relation to a refined model for aminoglycoside transport and briefly relative to plasmid-mediated aminoglycoside resistance.
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PMID:Aminoglycoside-resistant mutation of Pseudomonas aeruginosa defective in cytochrome c552 and nitrate reductase. 624 53

A nonspecific NADPH-dependent carbonyl reductase from human brain (formerly designated as aldehyde reductase 1; Ris, M. M., and von Wartburg, J. P. (1973) Eur. J. Biochem. 37, 69-77) has been purified to homogeneity. The enzyme reduces a number of biologically and pharmacologically active carbonyl compounds. Quinones, e.g. menadione, ubiquinone, and tocopherolquinone are the best substrates, followed by aldehydes containing an activated carbonyl moiety, e.g. 4-nitrobenzaldehyde or methylglyoxal. The enzyme also reduces ketones, e.g. prostaglandins of the E and A class, the anthracycline antibiotic daunorubicin and 3-ketosteroids. During catalysis the pro 4S hydrogen atom of the nicotinamide ring of NADPH is transferred to the substrate. Flavonoids, e.g. quercetin and rutin, indomethacin, ethacrynic acid, and dicoumarol inhibit the enzyme activity. 4-Hydroxymercuribenzoate and iodoacetate inactivate the enzyme. NADPH and substrate do not protect against the loss of activity. Carbonyl reductase consists of a single polypeptide chain with a molecular weight of 30,000. The native enzyme occurs in three molecular forms with similar substrate specificity and inhibitor sensitivity. The isoelectric points of the three enzyme species are 6.95, 7.85, and 8.5. In the presence of coenzyme the isoelectric points are shifted to 5.2 to 5.9. The comparison of structural and enzymic features of carbonyl reductase with other monomeric oxidoreductases suggests a close relationship of carbonyl reductase with prostaglandin 9-keto-reductase and xenobiotic ketone reductase.
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PMID:Purification and properties of an NADPH-dependent carbonyl reductase from human brain. Relationship to prostaglandin 9-ketoreductase and xenobiotic ketone reductase. 700 31

We analyzed lactate, pyruvate, and citric acid cycle intermediates in cerebrospinal fluid by high-performance liquid chromatography in Rett syndrome patients (n = 27; mean age, 5.7 +/- 3.4 years) and age-matched female controls (n = 12; mean age, 7.0 +/- 3.3 years). The lactate, pyruvate, alpha-ketoglutarate, and malate were significantly elevated in Rett syndrome compared to the controls. The lactate/pyruvate ratio was not different. On the other hand, cerebrospinal fluid citrate, cis-aconitate, succinate, fumarate, and oxaloacetate were not significantly different in Rett syndrome patients than in the controls. We also evaluated the correlation between these acids and clinical symptoms and signs, including clinical stage, seizures medications (anticonvulsants or naltrexone), developmental quotient, self-abuse, and hyperventilation or apnea or both. The concentrations of all these acids did not differ significantly with clinical stage. Lactate elevation significantly correlated with apnea. Lactate and pyruvate elevation significantly correlated with hyperventilation or with both breathing abnormalities. Our observations in this sample of patients with Rett syndrome led us to speculate that patients with the Rett syndrome may have defective carbohydrate metabolism. Elevated mitochondrial reduced nicotinamide-adenine dinucleotide-linked substrates suggest that reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase may be deficient in the brain in Rett syndrome patients.
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PMID:Abnormal carbohydrate metabolism in cerebrospinal fluid in Rett syndrome. 815 Oct 77

Acetolactate nonenzymatically reduced flavins, quinones and nicotinamide coenzymes in a time-dependent manner at physiological pH and moderate temperature. In the presence of excess acetolactate, the reduction of FAD and NAD+ followed pseudo-first-order kinetics. The rate of reduction was proportional to the concentration of acetolactate, and the rate constants at 37 degrees C and pH 7.5 were 4.8 x 10(-2) M-1 s-1 and 7.4 x 10(-3) M-1 s-1 for FAD and NAD+, respectively. In contrast, ubiquinone reduction followed pseudo-zero-order kinetics in the presence of excess acetolactate. At 37 degrees C and pH 7.5, the rate of reduction was proportional to the acetolactate concentration, and the apparent rate constant was 8.3 x 10(-6) s-1. In contrast to FAD, the rate of reduction of ubiquinone was higher at low pH. The kinetics of ubiquinone reduction suggested that the rate-limiting step was acetolactate decarboxylation and formation of the enolate anion, whereas the rate of FAD reduction was governed by the second-order reaction of the enolate anion. Following the oxidation, acetolactate was converted to diacetyl. Reduced FAD formed by the reaction with acetolactate generated a low rate of O2 consumption during assays of the oxygenase activity of acetohydroxy acid synthase. The reaction of acetolactate with quinones may provide a mechanism for the nonenzymatic formation diacetyl in whole milk.
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PMID:Nonenzymatic acetolactate oxidation to diacetyl by flavin, nicotinamide and quinone coenzymes. 854 13

Decreased activity of complex I (NAD:ubiquinone oxidoreductase) is the most frequent biochemical finding associated with mutation at the base pair 3243 of the mitochondrial DNA. The mutation has been previously shown to lead to a defective translation. We hypothesized that due to an imperfect assembly of complex I subunits the substrate affinity of this enzyme may be lowered and this may be counteracted by increasing the mitochondrial NAD+NADH concentration. Therefore, we studied the effect and mechanism of action of nicotinamide treatment in a MELAS patient with the base pair 3243 mutation. Nicotinamide treatment was initiated after his first stroke-like episode. The blood NAD concentration (representing the intracellular concentration in erythrocytes) increased linearly being 24-fold at 6 weeks of treatment. Blood lactate and pyruvate concentration decreased by 50% within three days and 24 h urine lactate content within 2 weeks and we observed a clinical improvement together with a decrease in the lesion volume in magnetic resonance imaging within the first month. The cellular NAD increase upon nicotinamide administration was probably universal, because it occurred in a time and dose-dependent manner in cultured fibroblasts from both the patient and the controls. Alleviation of the lactate accumulation during the nicotinamide treatment suggests that an increase in the cellular NAD+NADH concentration leads to enhancement of the oxidation of reducing equivalents. However, the Km of complex I for NADH in skeletal muscle from the patient was similar to that of controls. This may indicate that physiologically mitochondrial complex I operates at non-saturating substrate concentration, and this may explain the effect of nicotinamide treatment.
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PMID:Increase of blood NAD+ and attenuation of lactacidemia during nicotinamide treatment of a patient with the MELAS syndrome. 859 19

Water-suppressed chemical shift magnetic resonance imaging was used to detect neurochemical alterations in vivo in neurotoxin-induced rat models of Huntington's and Parkinson's disease. The toxins were: N-methyl-4-phenylpyridinium (MPP+), aminooxyacetic acid (AOAA), 3-nitropropionic acid (3-NP), malonate, and azide. Local or systemic injection of these compounds caused secondary excitotoxic lesions by selective inhibition of mitochondrial respiration that gave rise to elevated lactate concentrations in the striatum. In addition, decreased N-acetylaspartate (NAA) concentrations were noted at the lesion site over time. Measurements of lactate washout kinetics demonstrated that t1/2 followed the order: 3-NP approximately MPP+ >> AOAA approximately malonate, which parallels the expected lifetimes of the neurotoxins based on their mechanisms of action. Further increases in lactate were also caused by intravenous infusion of glucose. At least part of the excitotoxicity is mediated through indirect glutamate pathways because lactate production and lesion size were diminished using unilateral decortectomies (blockade of glutamatergic input) or glutamate antagonists (MK-801). Lesion size and lactate were also diminished by energy repletion with ubiquinone and nicotinamide. Lactate measurements determined by magnetic resonance agreed with biochemical measurements made using freeze clamp techniques. Lesion size as measured with MR, although larger by 30%, agreed well with lesion size determined histologically. These experiments provide evidence for impairment of intracellular energy metabolism leading to indirect excitotoxicity for all the compounds mentioned before and demonstrate the feasibility of small-volume metabolite imaging for in vivo neurochemical analysis.
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PMID:Non-invasive neurochemical analysis of focal excitotoxic lesions in models of neurodegenerative illness using spectroscopic imaging. 862 49

Cytosolic NADPH-dependent ubiquinone reductase (NADPH-UQ reductase) accounted for about 68% of the total ubiquinone (UQ) reductase activity in rat liver homogenate [Takahashi, T. et al. (1995) Biochem. J. 309, 883-890]. We investigated the effects of various factors on this enzyme activity in rat liver cytosol with the aim of elucidating its physiological roles. The NADPH-UQ reductase in rat liver cytosol catalyzed the reduction of UQ to UQH2 with concomitant oxidation of equimolar NADPH. The optimal pH was around 7.4, and the optimal temperatures were about 28 degrees C for NADH and about 37 degrees C for NADPH. NADH, deamino NADH, and deamino NADPH were much less active hydrogen donors than NADPH, whereas reduced nicotinamide mononucleotide, ascorbate, erythorbate, reduced glutathione, and cysteine were inactive. As the hydrogen acceptor, UQ-9 had the highest Vmax/Km among the long-chain UQ homologues tested. FAD and FMN stimulated the activity. Anionic detergents, Mg2+ and Sr2+ also enhanced the activity. Rotenone, malonic acid, antimycin A, and KCN, which inhibit mitochondrial and microsomal electron transfer enzymes, superoxide dismutase, and acetylated cytochrome c had no effect on the NADPH-UQ reductase activity. These results indicated that the NADPH-UQ reductase in rat liver cytosol is a flavoprotein that reduces UQ-10 by a two-electron reduction mechanism and is distinguishable from known microsomal and mitochondrial enzymes, as well as DT-diaphorase [EC 1.6.99.2].
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PMID:Characterization of NADPH-dependent ubiquinone reductase activity in rat liver cytosol: effect of various factors on ubiquinone-reducing activity and discrimination from other quinone reductases. 888 15


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