Increase In Coenzyme Research Articles

Effect of complexes of precursors and modulators of coenzyme q biosynthesis on functional state of old rats' heart mitochondria

Our research demonstrate that ageing leads to changes in activity of electron-transporting enzyme complexes in myocardial mitochondria of old rats and to increased sensitivity of mitochondrial permeability transition pore to inductors of its opening - Ca2+ and phenylarsine oxide. We also observed activation of lipid and protein free-radical peroxidation processes. Administration of a complex of biologically active substances that included precursors and modulators of coenzyme Q biosynthesis (α-tocopherol acetate, 4-hydroxybenzoic acid, and methionine) we observed the increase in coenzyme Q content, correction of functional activity of mitochondrial electron-transport chain enzyme complexes, the decrease in intensivity of lipid and protein free-radical peroxidation in the heart and the decrease in sensitivity of mitochondrial permeability transition pore to inductors of its opening. This complex may be used to treat mitochondrial dysfunction under numerous pathologies of cardiovascular system, as well as in ageing.

The effect of complexes of precursors and modulators of coenzyme Q biosynthesis on the functional state of heart mitochondria of old rats

Aging is accompanied by changes in activity of electron-transport enzyme complexes in myocardial mitochondria of old rats and by increased sensitivity of the mitochondrial permeability transition pore (MPTP) to inductors of its opening (Ca2+ and phenylarsine oxide). We also observed activation of lipid and protein free-radical peroxidation processes. Administration of a complex of biologically active substances that included precursors and modulators of coenzyme Q biosynthesis (α-tocopherol acetate, 4-hydroxybenzoic acid, and methionine) caused the increase in coenzyme Q content, correction of functional activity of mitochondrial electron-transport chain enzyme complexes, the decrease in intensity of lipid and protein free-radical peroxidation in the heart mitochondria and the decrease in sensitivity of mitochondrial permeability transition pore to inductors of its opening. This complex may be recommended for treatment of mitochondrial dysfunction in various pathologies of cardiovascular system, including in aging.

Chemotherapy induces an increase in coenzyme Q 10 levels in cancer cell lines

Free radicals have been implicated in the action of many chemotherapeutic drugs. Here we tested the hypothesis that camptothecin and other chemotherapeutic drugs, such as etoposide, doxorubicin, and methotrexate, induce an increase in coenzyme Q 10 levels as part of the antioxidant defense against free radical production under these anticancer treatments in cancer cell lines. Chemotherapy treatment induced both free radical production and an increase in coenzyme Q 10 levels in all the cancer cell lines tested. Reduced coenzyme Q 10 form levels were particularly enhanced. Coenzyme Q 10-increased levels were associated with up-regulation of COQ genes expression, involved in coenzyme Q 10 biosynthesis. At the translational level, COQ7 protein expression levels were also increased. Furthermore, coenzyme Q 10 biosynthesis inhibition blocked camptothecin-induced coenzyme Q 10 increase, and enhanced camptothecin cytotoxicity. Our findings suggest that coenzyme Q 10 increase is implicated in the cellular defense under chemotherapy treatment and may contribute to cell survival.

Concentrations in beef and lamb of taurine, carnosine, coenzyme Q 10, and creatine

Levels of taurine, carnosine, coenzyme Q 10, and creatine were measured in beef liver and several muscles of beef and lamb and in cooked and uncooked meat. The amino acid taurine has numerous biological functions, the dipeptide carnosine is a buffer as well as an antioxidant, coenzyme Q 10 is also an antioxidant present within mitochondria, and creatine along with creatine phosphate is involved with energy metabolism in muscle. Large differences were shown for all compounds between beef cheek muscle (predominantly red fibres) and beef semitendinosus muscle (mainly white fibres), with cheek muscle containing 9.9 times as much taurine, and 3.2 times as much coenzyme Q 10, but only 65% as much creatine and 9% as much carnosine. Levels in lamb relative to beef semitendinosus muscles were higher for taurine but slightly lower for carnosine, coenzyme Q 10 and creatine. Values for all the compounds varied significantly between eight lamb muscles, possibly due in part to differences in the proportion of muscle fibre types. Slow cooking (90 min at 70 °C) of lamb longissimus and semimembranosus muscles led to significant reductions in the content of taurine, carnosine, and creatine ( P<0.001), but a slight increase in coenzyme Q 10. There was also a four-fold increase in creatinine, presumably due to its formation from creatine. It is concluded that biologically, and possibly nutritionally, significant levels of taurine, carnosine, coenzyme Q 10, and creatine are present in beef and lamb, but that these levels vary between muscles, between animals, and with cooking.

Diabetes induces metabolic adaptations in rat liver mitochondria: role of coenzyme Q and cardiolipin contents

Several studies have been carried out to evaluate the alterations in mitochondrial functions of diabetic rats. However, results are sometimes controversial, since experimental conditions diverge, including age and strain of used animals. The purpose of this study was to evaluate the metabolic modifications in liver mitochondria, both in the presence of severe (STZ-treated rats) and mild hyperglycaemia [Goto–Kakizaki (GK) rats], when compared with control animals of similar age. Moreover, metabolic alterations were evaluated also at initial and advanced stages of the disease. We observed that both models of diabetes (type 1 and type 2) presented a decreased susceptibility of liver mitochondria to the induction of permeability transition (MPT). Apparently, there is a positive correlation between the severity of diabetes mellitus (and duration of the disease) and the decline in the susceptibility to MPT induction. We also found that liver mitochondria isolated from diabetic rats presented some metabolic adaptations, such as an increase in coenzyme Q and cardiolipin contents, that can be responsible for the observed decrease in the susceptibility to multiprotein pore (MPTP) opening.

Olive oil supplemented with vitamin E affects mitochondrial coenzyme Q levels in liver of rats after an oxidative stress induced by adriamycin.

In this study we have evaluated the supplementation of olive oil with vitamin E on coenzyme Q concentration and lipid peroxidation in rat liver mitochondrial membranes. Four groups of rats were fed on virgin olive, olive plus 200 mg/kg of vitamin E or sunflower oils as lipid dietary source. To provoke an oxidative stress rats were administered intraperitoneally 10 mg/kg/day of adriamycin the last two days of the experiment. Animals fed on olive oil plus vitamin E had significantly higher coenzyme Q and vitamin E levels but a lower mitochondrial hydroperoxide concentration than rats fed on olive oil. Retinol levels were not affected, by either different diets or adriamycin treatment. In conclusion, an increase in coenzyme Q and alpha-tocopherol in these membranes can be a basis for protection against oxidation and improvement in antioxidant capacity.

A Deficiency in Respiratory Complex I in Heart Mitochondria from Vitamin A-Deficient Rats Is Counteracted by an Increase in Coenzyme Q

Defects of NADH:coenzyme Q oxidoreductase (complex I) of mitochondria have been described in many congenital and acquired diseases. Administration of coenzyme Q (CoQ, ubiquinone) has been shown to benefit patients with some of these diseases. However, the mechanisms by which CoQ exerts the therapeutic effects are not clearly understood. A reason could be the lack of saturation of CoQ, in kinetic terms, for complex I activity. However, this hypothesis has not been provedin vivobecause of the difficulty to incorporate CoQ into the mitochondrial membranes. We have found a deficiency in respiratory complex I in heart mitochondria from vitamin A-deficient rats which was accompanied by high CoQ content. The defect in complex I activity was compensated by the increase in CoQ to maintain the mitochondrial electron transfer rate. This finding supports, for the first time in anin vivoexperimental approach, the kinetic hypothesis to explain the short-term therapeutic effects of CoQ.

A subcellular study of the clofibratei-nduced increase in coenzyme a concentration in rat liver

When clofibrate [ethyl 2-(4-chlorophenoxv)-2-methylpropionatel was administered subcutaneously to rats (600 mg kg per day for 3 days), the concentration of CoA and its acyl derivatives in the liver increased 2.5-fold. Forty-eight per cent of the total cellular CoA in the clofibrate-treated rat liver and 51 per cent in the control liver was found in the mitochondrial fraction. In order to study the intermediates of CoA synthesis, clofibrate-treated rats were injected with [ 3H]pantothenate intracardially and killed after 30 min, l or 2hr for determination of the incorporation of radioactivity into CoA and its precursors. The incorporation of pantothenate into CoA after 2 hr was 5.9-fold in the liver and 4.5-fold in the liver mitochondrial fraction as compared with the control values. Measurement of the pantothenate concentration and radioactivity in clofibrate-treated and control rat liver showed that the higher incorporation of [ 3H]pantothenate into CoA in clofibrate-treated rat liver cannot be the result of a higher specific radioactivity of pantothenate. It is therefore evident that clofibrate affects the CoA concentration by increasing the rate of synthesis, although the rate of CoA degradation is simultaneously decreased, as has been shown previously [9]. The present results indicate that clofibrate increases the total hepatic CoA concentration without affecting the intracellular compartmentation of CoA. The clofibrate-induced increase in the rate of CoA synthesis does not result in differences in the compartmentation of the intermediates of CoA synthesis.

Clofibrate-induced increase in coenzyme A concentration in rat tissues.

1. When clofibrate [ethyl 2-(4-chlorophenoxy)-2-methylpropionate] was administered subcutaneously to rats (600mg/kg per day for 5 days), the concentration of CoA and its acyl derivatives increased in several tissues. The increase in total CoA was 3.2-fold in the liver, 1.8-fold in the kidney, 2.7-fold in the heart and 2.4-fold in skeletal muscle. 2. To study the mechanism of this phenomenon, clofibrate-treated rats were injected with [(3)H]pantothenate intracardially and killed after 15min, 30min, 1 and 2h and 1, 3, 5 and 7 days for the determination of the incorporation of radioactivity into CoA and its precursors. Incorporation into CoA after 2h was 6.2-fold in the liver as compared with the control values and 4.6-fold in the kidneys. 3. The disappearance of the label from CoA was very slow compared with the rate of incorporation; it exhibited exponential kinetics, and was slower in the livers of the clofibrate-treated rats (t((1/2)) 18.2 days) than in the controls (t((1/2)) 5.6 days). 4. The rate of CoA degradation, calculated from the calculated rate constants of the apparent first-order kinetics of the disappearance of the label and from the CoA pool sizes, was approximately the same in the clofibrate-treated animals (11.5pmol/min per g), and the controls (11.6pmol/min per g). 5. These rates of CoA degradation indicate that the effect of clofibrate on CoA concentration may be mainly due to inhibition of the enzymes of CoA degradation, although recycling of the label cannot be excluded. The increase in the rate of pantothenate incorporation into CoA suggests that clofibrate also increases the synthesis of CoA.

Demonstration of cobamide coenzyme in Ascaris suum

1. 1. Cobamide coenzyme was extracted from the body wall of adult female Ascaris suum maintained in Ellison's medium containing vitamin B 12. 2. 2. The identification of the coenzyme in purified fractions was based on (a) specific spectral changes following treatment of the preparation with light and cyanide, (b) coenzyme activity in the glutamate mutase reaction and (c) inactivation of the coenzyme activity by light. 3. 3. A fivefold increase in coenzyme occurred in worms maintained in Ellison's medium plus vitamin B 12, compared to the endogenous value. The data indicate that vitamin B 12 is converted by A. suum into the metabolically active coenzyme.

Quantitative histochemical distribution of coenzyme A in the rat adrenal in various functional states.

Modifications of the procedure of Malmstrom and Glick for the micro measurement of coenzyme A were employed in a study of the quantitative histological distribution of the coenzyme in adrenal glands of male albino rats. Subcutaneous injection of 25 mg. ACTH per kg. 3 hours before sacrifice produced significant increases in coenzyme A concentration in the adjoining zones between the glomerulosa and fasciculata, and the fasciculata and reticularis. Small increases occurred in the medulla and the reticular-medullary border zone. Subcutaneous injection of 5 mg. calcium-d-pantothenate 3 hours before sacrifice increased the coenzyme concentration in all zones except the adjacent fascicular-reticular regions. Analysis of whole gland homogenates prepared from adrenals of animals killed at noon and at midnight revealed that the coenzyme concentration was about 100 per cent greater in the latter. Injection of ACTH abolished day-night differences by producing maximal concentrations in both groups. Injection of panto...