Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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A total of 109 patients with symptomatic essential hypertension presenting to a private cardiology practice were observed after the addition of CoQ10 (average dose, 225 mg/day by mouth) to their existing antihypertensive drug regimen. In 80 per cent of patients, the diagnosis of essential hypertension was established for a year or more prior to starting CoQ10 (average 9.2 years). Only one patient was dropped from analysis due to noncompliance. The dosage of CoQ10 was not fixed and was adjusted according to clinical response and blood CoQ10 levels. Our aim was to attain blood levels greater than 2.0 micrograms/ml (average 3.02 micrograms/ml on CoQ10). Patients were followed closely with frequent clinic visits to record blood pressure and clinical status and make necessary adjustments in drug therapy. Echocardiograms were obtained at baseline in 88% of patients and both at baseline and during treatment in 39% of patients. A definite and gradual improvement in functional status was observed with the concomitant need to gradually decrease antihypertensive drug therapy within the first one to six months. Thereafter, clinical status and cardiovascular drug requirements stabilized with a significantly improved systolic and diastolic blood pressure. Overall New York Heart Association (NYHA) functional class improved from a mean of 2.40 to 1.36 (P < 0.001) and 51% of patients came completely off of between one and three antihypertensive drugs at an average of 4.4 months after starting CoQ10. Only 3% of patients required the addition of one antihypertensive drug. In the 9.4% of patients with echocardiograms both before and during treatment, we observed a highly significant improvement in left ventricular wall thickness and diastolic function.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Aspects Med 1994
PMID:Treatment of essential hypertension with coenzyme Q10. 775 51

This study investigated the biosynthesis of ubiquinone in isolated and perfused hearts of young and aged rats exposed to ischemia and reperfusion. A first group of hearts was used to determine the changes in coenzyme Q9 (CoQ9) and coenzyme Q10 (CoQ10) concentrations at mitochondrial and microsomal level after 30 min of ischemia (98% reduction of the preischemic flow) and 60 min of reperfusion. A second group was utilized to evaluate the rate of CoQ9 and CoQ10 biosynthesis in the membranes by dissolving two ubiquinone precursors, p-OH-[U-14C]benzoate and mevalonolactone, in the perfusion buffer. The hearts were aerobically perfused for 60 min in the presence of the precursors either immediately after the equilibration period or following 30 min ischemia. The young rat hearts showed a 30% reduction in the mitochondrial levels of CoQ9 after ischemia and reperfusion with respect to the preischemic values (P < 0.05 and P < 0.01, respectively). On the contrary, the mitochondrial CoQ9 content was not modified under these conditions in the aged hearts. At the end of reperfusion, the biosynthesis of mitochondrial CoQ9 and CoQ10 was higher in the young rats (P < 0.05), and lower in the aged rats (P < 0.05), with respect to the aerobic perfusion. In both young and aged rats minor changes in CoQ9 concentrations and biosynthesis were observed at microsomal level. These results indicate that myocardial reperfusion decreases the mitochondrial content of ubiquinone and stimulates CoQ9 biosynthesis in young rats but not in aged rats.
J Mol Cell Cardiol 1995 Jan
PMID:Adaptive changes in coenzyme Q biosynthesis to myocardial reperfusion in young and aged rats. 776 Mar 52

Ubiquinone (coenzyme Q, CoQ) was analyzed and individual homologues quantified in 11 species of parasitic and free-living protozoa by a combination of thin-layer chromatography and high performance liquid chromatography. Fast atom bombardment ionization-mass spectrometry was used for the first time to confirm the identity of the fractionated CoQ homologues and proved to be a fast, gentle and convenient method for ubiquinone identification. Ubiquinone was detected in all organisms including those devoid of identifiable mitochondria. However, significantly lower levels of CoQ were present in those organisms lacking this respiratory organelle (5- to 50-fold lower in Entamoeba histolytica (CoQ9) and 15- to 350-fold for Giardia lamblia (CoQ9) and Tritrichomonas foetus (CoQ10)). Coenzyme Q9 was the predominant homologue in promastigotes of Leishmania donovani and Leishmania major. Lower amounts of CoQ8 and CoQ10 were also detected in L. donovani, and CoQ8 in L. major. Comparison of the in vitro cultivated promastigote and amastigote forms of Leishmania pifanoi and Leishmania amazonensis revealed CoQ9 to be the sole detectable ubiquinone homologue in the amastigote (macrophage) stage, whereas CoQ8 and CoQ10 were also present in the promastigotes (life cycle stage found in the insect gut) of L. pifanoi, and CoQ7 and CoQ8 in promastigotes of L. amazonensis. Interestingly, the total amounts of CoQ were similar in both forms of these organisms. The free-living ciliates, Tetrahymena thermophila and Paramecium tetraurelia contained CoQ8 as the predominant ubiquinone species and this homologue was also present in the isolated cilia from P. tetraurelia. The marine ciliate, Parauronema acutum contained CoQ7 as well as CoQ8. Comparison of xenosome-containing P. acutum with organisms lacking the symbiont revealed that twice the level of CoQ8 was present in cells grown with this cytoplasmic gram-negative bacterium. Results suggest that CoQ is ubiquitous amongst the protozoa, regardless of the presence of mitochondria, and may function in alternative roles to that of mitochondrial electron transport chain component.
Mol Biochem Parasitol 1994 Jun
PMID:Detection of ubiquinone in parasitic and free-living protozoa, including species devoid of mitochondria. 796 63

We have investigated the effect of rat liver perfusion with adriamycin on mitochondrial activities. Although the perfusion treatment per se induces some decline of respiratory activities, adriamycin strongly potentiates this effect; moreover the coenzyme Q9 content of the mitochondrial membrane is significantly lowered by the antibiotic. Coaddition of coenzyme Q10 in the perfusate significantly protects the mitochondria, not only from loss of respiratory activities but also of the endogenous CoQ9 content. Exogenous CoQ10 fails to enhance respiratory activities in control rats, not treated with adriamycin, even though CoQ concentration has been proven not to be kinetically saturating in the respiratory chain under physiological conditions. Thus, the beneficial effect of CoQ10 in the perfusate does not appear to be the result of its role in the respiratory chain but is a consequence of its antioxidant action.
Biochem Mol Biol Int 1994 Jul
PMID:Protective effect of exogenous coenzyme Q against damage by adriamycin in perfused rat liver. 798 50

Pyruvate is conventionally used as a key growth supplement for mammalian rho 0 cells that lack mitochondrial DNA and are thereby devoid of oxidative phosphorylation. We have tested the proposition that cultured rho 0 human cells can be grown using redox compounds other than pyruvate. The results show that potassium ferricyanide and coenzyme Q10 can each be used to replace pyruvate to support the growth of rho 0 Namalwa cells (a lymphoblastoid cell line). Ferricyanide and coenzyme Q10 have both been reported as substrates for a plasma membrane NADH oxidase system which is capable of re-oxidising cytosolic NADH to NAD+. These compounds are also known to stimulate the activity of this enzyme system. We interpret our data to indicate that redox support for growth of rho 0 human cells can be achieved by external electron acceptors such as ferricyanide (a plasma membrane impermeant compound), or coenzyme Q10 (an integral component of the plasma membrane oxidase), through the enhanced conversion of cytosolic NADH to NAD+. This re-oxidation of NADH enables glycolysis to function efficiently as the sole source of cellular ATP, in the absence of mitochondrial oxidative phosphorylation in rho 0 cells. This has important implications for the development of new strategies for the amelioration of the bioenergy decline that occurs in mitochondrial disease and during the human ageing process.
Biochem Mol Biol Int 1993 Dec
PMID:Growth of rho 0 human Namalwa cells lacking oxidative phosphorylation can be sustained by redox compounds potassium ferricyanide or coenzyme Q10 putatively acting through the plasma membrane oxidase. 819 3

Pharmacological intervention was investigated into the age-associated decline in mitochondrial function. Rats aged 7 weeks were divided into two groups; the control group (standard diet), and the coenzyme Q10 group (fed with 0.2% coenzyme Q10 diet). Mitochondria from skeletal muscle (psoai major) and cardiac muscle were prepared from rats aged 7, 35, and 55 weeks, and enzymic activities were measured in four complexes of the mitochondrial electron transport chain. Age-associated declines in activities of complexes I and IV of psoai major were significantly mitigated in the coenzyme Q10 group. The activities of complexes I and IV of heart mitochondria did not change significantly throughout the experiment in either group. Moreover, aging up to 55 weeks had no significant effect on activities of complexes II and III in either tissue. It is concluded that intake of a coenzyme Q10 rich diet might retard the normally observed age-associated decline in overall mitochondrial respiratory function in rat skeletal muscle.
Biochem Mol Biol Int 1995 Dec
PMID:Preservation of mitochondrial respiratory function by coenzyme Q10 in aged rat skeletal muscle. 874 41

Thirty-five (35) healthy physically active males had muscle biopsies taken from their vastus lateralis muscle to analyze for ubiquinone (vitamin Q, UQ), oxidative (muscle fiber types expressed as %ST and citrate synthase activity, CS) and fermentative (lactate dehydrogenase, LD) profiles. Graded cycle ergometer exercise to determine the intensities corresponding to onset of blood lactate accumulation set to 4.0 mmol x l-1 (WOBLA) and symptom limited exercise ('maximal', WSL) were also undertaken. Eleven (11) subjects had also recently participated in a marathon race. UQ was positively related to CS (r = 0.67, p < 0.001) and %ST (r = 0.60, p < 0.001) but not to LD. UQ was also positively related to exercise capacity and/or marathon performance (e.g. WOBLA x kg-1 BW, r = 0.70, p < 0.001). It was suggested that muscle UQ allocation in man was related to variables describing molecular oxygen availability, respiratory activity and oxidative energy releasing processes but not to fermentation activity. UQ allocation to ST fibers/CS activity was suggested to be due to the double role of UQ: 1) as a mitochondrial coenzyme (CoQ10) and 2) as a nonspecific antioxidant.
Mol Cell Biochem 1996 Mar 23
PMID:Muscle ubiquinone in healthy physically active males. 909 74

To establish a system for over-production of PSII-L protein which is a component of photosystem II (PSII) complex, a plasmid designated as pMAL-psbL was constructed and expressed in Escherichia coli JM109. A fusion protein of PSII-L and maltose-binding proteins (53 kDa on SDS-PAGE) was accumulated in E. coli cells to a level of 10% of the total protein upon isopropyl-beta-D-thiogalactopyranoside (IPTG) induction. The carboxyl-terminal part of 5.0 kDa was cleaved from the fusion protein and purified by an anion exchange column chromatography in the presence of detergents. This 5.0 kDa protein was identified as PSII-L by amino-terminal amino acid sequence analysis and the chromatographic behavior on an anion exchange gel. A few types of mutant PSII-L were also prepared by the essentially same procedure except for using plasmids which contain given mutations in psbL gene. Plastoquinone-9 (PQ-9) depleted PSII reaction center core complex consisting of D1, D2, CP47, cytochrome b-559 (cyt b-559), PSII-I and PSII-W was reconstituted with PQ-9 and digalactosyldiglyceride (DGDG) together with the wild-type or mutant PSII-L produced in E. coli or isolated PSII-L from spinach. Significant difference between the wild-type PSII-L proteins from E. coli and spinach was not recognized in the effectiveness to recover the photo-induced electron transfer activity in the resulting complexes. The analysis of stoichiometry of PQ-9 per reaction center in the PQ-9 reconstituted PS II revealed that two molecules of PQ-9 were reinserted into a reaction center independent of the presence or absence of PSII-L. These results suggest that PSII-L recovers the electron transfer activity in the reconstituted RC by a mechanism different from the stabilization of PQ-9 in the Q(A) site of PSII. Ubiquinone-10 (UQ-10), but not plastoquinone-2 (PQ-2), substituted PQ-9 for recovering the PSII-L supported electron transfer activity in the reconstituted PSII reaction center complexes. The results obtained with the mutant PSII-L proteins revealed that the carboxyl terminal part rather than amino terminal part of PSII-L is crucial for recovering the electron transfer activity in the reconstituted complexes.
Plant Mol Biol 1997 May
PMID:Role of PSII-L protein (psbL gene product) on the electron transfer in photosystem II complex. 1. Over-production of wild-type and mutant versions of PSII-L protein and reconstitution into the PSII core complex. 917 21

The experiments reported here were undertaken to test the hypothesis that the antioxidative, reduced form of hydrophobic phase coenzyme Q (CoQ) may be generated and maintained by the two-electron quinone reductase, DT-diaphorase [NAD(P)H:(quinone-acceptor) oxidoreductase, EC 1.6.99.2] by catalyzing formation of the hydroquinone form of CoQ. This enzyme was isolated and purified from rat liver cytosol and its reduction of several CoQ homologs incorporated into large unilamellar vesicles (LUVETs) was demonstrated. The addition of NADH and DT-diaphorase to LUVETs and to multilamellar vesicles (MLVs) containing CoQ homologs, including CoQ9 and CoQ10, resulted in essentially complete reduction of the CoQ. Incorporation of either CoQ9H2 or CoQ10H2 and the lipophylic radical generator 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN) into MLVs in the presence of DT-diaphorase and NADH maintained the reduced state of CoQ and inhibited lipid peroxidation. The reaction between DT-diaphorase and CoQ was also demonstrated in isolated rat liver hepatocytes in which incorporation of CoQ10 provided protection from adriamycin (adr)-induced mitochondrial membrane damage. The role of DT-diaphorase in the antioxidant activity of CoQ was demonstrated by the co-incorporation of dicoumarol (dic), a potent inhibitor of DT-diaphorase, resulting in a loss of protection by incorporated CoQ10. These results support the antioxidant function of DT-diaphorase in both artificial and natural membrane systems by acting as a two-electron CoQ reductase which forms and maintains CoQ in the reduced state.
Mol Aspects Med 1997
PMID:The two-electron quinone reductase DT-diaphorase generates and maintains the antioxidant (reduced) form of coenzyme Q in membranes. 926 2

The coenzyme Q (CoQ) concentration in the inner membrane of beef heart mitochondria is not kinetically saturating for NADH oxidation inasmuch as the K(m) of NADH oxidation for endogenous CoQ10 is in the mM range in membrane lipids. Using CoQ1 as an electron acceptor from complex I, we have found additional evidence that the high Km of NADH oxidase for CoQ is not an artifact due to the use of organic solvents in reconstitution studies. We have also obtained experimental evidence that CoQ concentration may be rendered more rate-limiting for NADH oxidation either by a decrease of CoQ content (as in liver regeneration or under an acute oxidative stress), or by a possible increase of the Km for CoQ, as in some mitochondrial diseases and ageing. The possibility of enhancing the rate of NADH oxidation by CoQ therapy is hindered by the fact that the CoQ concentration in mitochondria appears to be regulated by its mixability with the membrane phospholipids. Nevertheless CoQ10 incorporated into heart submitochondrial particles by sonication enhances NADH oxidation (but not succinate oxidation) up to twofold. Nontoxic CoQ homologs and analogs having shorter side-chains with respect to CoQ10 can be incorporated in the mitochondrial membrane without sonication, supporting an enhancement of NADH oxidation rate above 'physiological' values. It is worth investigating whether this approach can have a therapeutical value in vivo in mitochondrial bioenergetic disorders.
Mol Aspects Med 1997
PMID:Coenzyme Q deficiency in mitochondria: kinetic saturation versus physical saturation. 926 3


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