Analytical method for ubiquinone-9 and ubiquinone-10 in rat tissues by liquid chromatography/turbo ion spray tandem mass spectrometry with 1-alkylamine as an additive to the mobile phase

We investigated the application of 1-alkylamines, as additives to the mobile phase, to a quantification method for ubiquinone-9 (CoQ9) and ubiquinone-10 (CoQ10) in rat thigh muscle and heart using liquid chromatography-tandem mass spectrometry (LC-MS/MS). In the optimization of the analytical method, we found that 1-alkylamines mixed with CoQ9 and CoQ10 in the turbo ion sprayed solution formed the 1-alkylammonium adduct molecules of these compounds during the ionization process and that the intensity of the adduct ions was considerably higher than that of the protonated molecules ([M+H]+) of these compounds. Furthermore, we investigated a variety of 1-alkylamines in the mobile phase for LC-MS/MS analysis to select the most appropriate 1-alkylamine for higher sensitivities of CoQ9 and CoQ10. After these examinations, we found that methylamine was the most suitable additive for the mobile phase, allowing a 12.5-fold gain in signal intensity in the full ion mass spectrum compared with that without methylamine. The internal standard (IS) used was ubiquinone-11 (CoQ11) for each analyte. The analytes and IS were extracted with methanol from the tissue homogenates at neutral pH and were injected into an LC-MS/MS with a turbo ion spray interface. The calibration curves for CoQ9 (5-500 microg/g in thigh muscle and 50-10,000 microg/g in heart) and CoQ10 (1-500 microg/g in thigh muscle and 10-10,000 microg/g in heart) showed good linearity. The method was precise; the relative standard deviations of the method for rat thigh muscle were not more than 13.5 and 9.0% for CoQ9 and CoQ10, respectively, and those for rat heart were not more than 6.7 and 5.4% for CoQ9 and CoQ10, respectively. The accuracies of the method for both rat thigh muscle and heart were good, with the deviations between the nominal concentration and calculated concentration of CoQ9 and CoQ10 typically being within 12.3 and 4.3%, respectively. This method provided reliable concentration levels for CoQ9 and CoQ10 in rat thigh muscle and heart.     

Primary coenzyme Q10 deficiency and the brain

Our findings in 19 new patients with cerebellar ataxia establish the existence of an ataxic syndrome due to primary CoQ10 deficiency and responsive to CoQ10 therapy. As all patients presented cerebellar ataxia and cerebellar atrophy, this suggests a selective vulnerability of the cerebellum to CoQ10 deficiency. We investigated the regional distribution of coenzyme Q10 in the brain of adult rats and in the brain of one human subject. We also evaluated the levels of coenzyme Q9 (CoQ9) and CoQ10 in different brain regions and in visceral tissues of rats before and after oral administration of CoQ10. Our results show that in rats, amongst the seven brain regions studied, cerebellum contains the lowest level of CoQ. However, the relative proportion of CoQ10 was the same (about 30% of total CoQ) in all regions studied. The level of CoQ10 is much higher in brain than in blood or visceral tissue, such as liver, heart, or kidney. Daily oral administration of CoQ10 led to substantial increases of CoQ10 concentrations only in blood and liver. Of the four regions of one human brain studied, cerebellum again had the lowest CoQ10y concentration.     

Distribution of antioxidants among blood components and lipoproteins: significance of lipids/CoQ10 ratio as a possible marker of increased risk for atherosclerosis.

Total CoQ10 levels were evaluated in whole blood and in plasma obtained from a group of 83 healthy donors. Extraction with light petroleum ether/methanol was more efficient, for whole blood, than the extraction which is often used for plasma and serum, i.e., ethanol hexane. An excellent correlation was present between plasma CoQ10 and whole blood CoQ10. CoQ10 is mainly associated with plasma rather than with cellular components. Positive, significant correlations were found between the LDL-chol/CoQ10 ratio and the total-chol/HDL-chol ratio, which is usually considered a risk factor for atherosclerosis. The proportion of CoQ10 carried by LDL was 58 +/- 10%, while the amount carried by HDL was 26 +/- 8%. In VLDL + IDL CoQ10 was 16 +/- 8%. The content of CoQ10 in single classes of lipoproteins is strictly correlated with CoQ10 plasma concentration. In a parallel study conducted on a population of diabetic patients (one IDDM group and one NIDDM) CoQ10 plasma levels were generally higher compared to the control group, also when normalised to total cholesterol. In particular the LDL fraction showed a CoQ10/chol ratio higher in NIDDM but not in IDDM patients, compared to controls. The CoQ10/triglycerides ratio was lower in NIDDM respect to controls and even lower in IDDM patients.     

Metabolic engineering of coenzyme Q by modification of isoprenoid side chain in plant

Coenzyme Q (CoQ), an electron transfer molecule in the respiratory chain and a lipid-soluble antioxidant, is present in almost all organisms. Most cereal crops produce CoQ9, which has nine isoprene units. CoQ10, with 10 isoprene units, is a very popular food supplement. Here, we report the genetic engineering of rice to produce CoQ10 using the gene for decaprenyl diphosphate synthase (DdsA). The production of CoQ9 was almost completely replaced with that of CoQ10, despite the presence of endogenous CoQ9 synthesis. DdsA designed to express at the mitochondria increased accumulation of total CoQ amount in seeds.     

Effects of various squalene epoxides on coenzyme Q and cholesterol synthesis

2,3-Oxidosqualene is an intermediate in cholesterol biosynthesis and 2,3:22,23-dioxidosqualene act as the substrate for an alternative pathway that produces 24(S),25-epoxycholesterol which effects cholesterol homeostasis. In light of our previous findings concerning the biological effects of certain epoxidated all-trans-polyisoprenes, the effects of squalene carrying epoxy moieties on the second and third isoprene residues were investigated here. In cultures of HepG2 cells both monoepoxides of squalene and one of their hydrolytic products inhibited cholesterol synthesis and stimulated the synthesis of coenzyme Q (CoQ). Upon prolonged treatment the cholesterol content of these cells and its labeling with [³H]mevalonate were reduced, while the amount and labeling of CoQ increased. Injection of the squalene monoepoxides into mice once daily for 6 days elevated the level of CoQ in their blood, but did not change the cholesterol level. The same effects were observed upon treatment of apoE-deficient mice and diabetic GK-rats. This treatment increased the hepatic level of CoQ10 in mice, but the amount of CoQ9, which is the major form, was unaffected. The presence of the active compounds in the blood was supported by the finding that cholesterol synthesis in the white blood cells was inhibited. Since the ratio of CoQ9/CoQ10 varies depending on the experimental conditions, the cells were titrated with substrate and inhibitors, leading to the conclusion that the intracellular isopentenyl-PP pool is a regulator of this ratio. Our present findings indicate that oxidosqualenes may be useful for stimulating both the synthesis and level of CoQ both in vitro and in vivo.     

A superior analysis of coenzyme Q10 in blood of humans, rabbits and rats for research

The quantitative analysis of coenzyme Q10 (CoQ10) in samples of whole human blood has been refined to allow a 2- to 3-fold increase in the number of analyses per day, and reduction of cost to approximately 15% of the previous cost. The method is simple yet maintains reliability. The standard error was 0.2% (n = 6). The variation in blood levels of CoQ10 for human subjects for each of three months was approximately 5% in comparison with the control value (n = 5). For 30 human males, of 18-50 years (26 +/- 6) in age, and for 30 human females, of 18-50 years (26 +/- 9), the mean blood level of CoQ10 was 0.71 +/- 0.13 microgram/ml and 0.70 +/- 0.18 microgram/ml respectively. The mean blood levels of CoQ10 of rabbits (n = 28) was 0.29 +/- 0.07 micrograms/ml, and that for rats (n = 29) was 0.23 +/- 0.03 micrograms/ml.     

Deficit of coenzyme Q in heart and liver mitochondria of rats with streptozotocin-induced diabetes

Mitochondrial dysfunction and oxidative stress participate in the development of diabetic complications, however, the mechanisms of their origin are not entirely clear. Coenzyme Q has an important function in mitochondrial bioenergetics and is also a powerful antioxidant. Coenzyme Q (CoQ) regenerates alpha-tocopherol to its active form and prevents atherogenesis by protecting low-density lipoproteins against oxidation. The aim of this study was to ascertain whether the experimentally induced diabetes mellitus is associated with changes in the content of endogenous antioxidants (alpha-tocopherol, coenzymes Q9 and Q10) and in the intensity of lipoperoxidation. These biochemical parameters were investigated in the blood and in the isolated heart and liver mitochondria. Diabetes was induced in male Wistar rats by a single intravenous injection of streptozotocin (45 mg x kg(-1)), insulin was administered once a day for 8 weeks (6 U x kg(-1)). The concentrations of glucose, cholesterol, alpha-tocopherol and CoQ homologues in the blood of the diabetic rats were increased. The CoQ9/cholesterol ratio was reduced. In heart and liver mitochondria of the diabetic rats we found an increased concentration of alpha-tocopherol, however, the concentrations of CoQ9 and CoQ10 were decreased. The formation of malondialdehyde was enhanced in the plasma and heart mitochondria. The results have demonstrated that experimental diabetes is associated with increased lipoperoxidation, in spite of the increased blood concentrations of antioxidants alpha-tocopherol and CoQ. These changes may be associated with disturbances of lipid metabolism in diabetic rats. An important finding is that heart and liver mitochondria from the diabetic rats contain less CoQ9 and CoQ10 in comparison with the controls. We suppose that the deficit of coenzyme Q can participate in disturbances of mitochondrial energy metabolism of diabetic animals.     

CoQ10 supplementation elevates the epidermal CoQ10 level in adult hairless mice

We have already shown that prolonged supplementation of CoQ(10) in humans reduces the wrinkle area rate and wrinkle volume per unit area in the corner of the eye. CoQ(10) supplementation is known to increase the CoQ(10) level in serum and in many organs; however, the level of CoQ(10) in skin has not yet been fully investigated yet. We examined whether CoQ(10) intake elevates the CoQ(10) and CoQ(9) levels in epidermis, dermis, serum and other organs (kidney, heart, brain, muscle and crystalline lens) in 43-week-old hairless male mice. We also established a method using a high performance liquid chromatograph equipped with an electrochemical detector (HPLC-ECD) to simultaneously quantify CoQ(9) and CoQ(10) in the tissues. CoQ(10) (0, 1, 100 mg/kg p.o.) was administered daily for 2 weeks. CoQ(10) supplementation of 100 mg/kg increased the serum and epidermal CoQ(10) levels significantly, but did not increase the CoQ(10) levels in either dermis or other organs. In conclusion, we showed that CoQ(10) intake elevates the epidermal CoQ(10) level, which may be a prerequisite to the reduction of wrinkles and other benefits related to the potent antioxidant and energizing effects of CoQ(10) in skin.     

Dose ranging and efficacy study of high-dose coenzyme Q10 formulations in Huntington's disease mice

There is substantial evidence that a bioenergetic defect may play a role in the pathogenesis of Huntington's Disease (HD). A potential therapy for remediating defective energy metabolism is the mitochondrial cofactor, coenzyme Q10 (CoQ10). We have reported that CoQ10 is neuroprotective in the R6/2 transgenic mouse model of HD. Based upon the encouraging results of the CARE-HD trial and recent evidence that high-dose CoQ10 slows the progressive functional decline in Parkinson's disease, we performed a dose ranging study administering high levels of CoQ10 from two commercial sources in R6/2 mice to determine enhanced efficacy. High dose CoQ10 significantly extended survival in R6/2 mice, the degree of which was dose- and source-dependent. CoQ10 resulted in a marked improvement in motor performance and grip strength, with a reduction in weight loss, brain atrophy, and huntingtin inclusions in treated R6/2 mice. Brain levels of CoQ10 and CoQ9 were significantly lower in R6/2 mice, in comparison to wild type littermate control mice. Oral administration of CoQ10 elevated CoQ10 plasma levels and significantly increased brain levels of CoQ9, CoQ10, and ATP in R6/2 mice, while reducing 8-hydroxy-2-deoxyguanosine concentrations, a marker of oxidative damage. We demonstrate that high-dose administration of CoQ10 exerts a greater therapeutic benefit in a dose dependent manner in R6/2 mice than previously reported and suggest that clinical trials using high dose CoQ10 in HD patients are warranted.     

Difference in antioxidant activity between reduced coenzyme Q9 and reduced coenzyme Q10 in the cell: studies with isolated rat and guinea pig hepatocytes treated with a water-soluble radical initiator.

A possible difference in antioxidant activity between reduced coenzyme Q9 (CoQ9H2) and reduced coenzyme Q10 (CoQ10H2) in animal cells was studied by incubation of hepatocytes with a hydrophilic radical initiator, 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH). Two kinds of hepatocytes differing in their content of CoQ homologs were used: rat, total (oxidized plus reduced) CoQ9: total CoQ10 6:1, guinea pig, 1:5. The sum of total CoQ9 and CoQ10 in rat and guinea-pig hepatocytes was about 780 and 400 pmol/mg protein, respectively. The concentration of CoQ9H2 in rat hepatocytes decreased linearly after the addition of AAPH, whereas that of oxidized CoQ9 showed a reciprocal increase. No loss of cell viability or increase of lipid peroxidation was observed until most of the CoQ9H2 had been consumed. Cellular CoQ9H2 was consumed probably through scavenging of lipid peroxyl radicals produced by incubation with AAPH. On the other hand, CoQ10H2 was not significantly consumed in the AAPH-treated rat hepatocytes during incubation compared with the control cells. In guinea-pig hepatocytes, cellular CoQ10H2 as well as CoQ9H2 was consumed by addition of AAPH. alpha-Tocopherol also showed linear consumption with incubation time regardless of the cell types used. It is concluded that CoQ9H2, together with alpha-tocopherol, constantly acts as a potential antioxidant in hepatocytes when incubated with AAPH, whereas CoQ10H2 mainly exhibits its antioxidant activity in cells containing CoQ10 as the predominant CoQ homolog.     

A modified determination of coenzyme Q10 in human blood and CoQ10 blood levels in diverse patients with allergies

Two situations required a modified determination of coenzyme Q10 (CoQ10) in human blood and organ tissue. Blood from patients with AIDS and cancer raised apprehensions about safety to an analyst, and the number of specimens for analysis is increasing enormously. A modified determination replaces silica gel-TLC with disposable Florisil columns, and steps were simplified to allow more analyses per unit time. Data from the modified determination are quantitatively compatible with data from older and tedious procedures. This determination was used for blood from 36 diverse patients with allergies. The mean CoQ10 blood level of these patients is not different from the mean level of so-called normal individuals, but approximately 40% (14/36) of these allergic patients had levels up to 0.65 micrograms/ml, which is the level of dying class IV cardiac patients. The biosynthesis of CoQ10 in human tissues is a complex process that requires several vitamins and micronutrients, so that countless vitamin-unsupplemented Americans may be deficient in CoQ10. The relationship of allergies to autoimmune mechanisms and immunity, and the established relationship of CoQ10 to immune states, may be a rationale for therapeutic trials of administering CoQ10 to patients with allergies who have low CoQ10 blood levels and are very likely deficient.     

Changes in the content and intracellular distribution of coenzyme Q homologs in rabbit liver during growth

In order to determine whether coenzyme Q (CoQ) homologs which coexist in mammals play the same or different roles, the concentrations of coenzyme Q9 (CoQ9) and coenzyme Q10 (CoQ10) were analyzed in Japanese White (JW) rabbit tissues during growth, together with the intracellular distribution of these two CoQ homologs. In liver %CoQ9 (total [CoQ9] X 100/total [CoQ9] + total [CoQ10]) was approx. 40% until 3 weeks after birth, and then gradually decreased to 20%. In kidney, %CoQ9 decreased from 8% (1 week) to 1% (7 weeks). In heart, %CoQ9 was 3%, and in the brain, 2%, and these values did not change with growth. Most CoQ9 was present in the cytosolic fraction, whereas most CoQ10 was in the mitochondrial fraction. There was but minor change in the intracellular distribution of CoQ9 and CoQ10 in rabbit liver between 2 weeks and 7 weeks of age. These results suggest that CoQ9 and CoQ10 may play different roles in their physiological actions as antioxidant or component of the mitochondrial respiratory chain.     

Reinvestigation of coenzyme Q10 isolation from Sporidiobolus johnsonii

There is considerable current interest in coenzyme Q10 (CoQ10) from a medical perspective. CoQ10 has been shown to alleviate the side effects of statin drugs, for instance, and so there is a push to find naturally high producers of the compound. Sporidiobolus johnsonii (S. johnsonii) has been reported to produce CoQ10 in studies that used only standards on thin‐layer chromatography (TLC) and also suggested the production of coenzyme Q9 (CoQ9). This work set out to verify CoQ9/CoQ10 production in S. johnsonii and quantify as appropriate. We show that S. johnsonii produces CoQ10 but found no evidence for CoQ9 biosynthesis. The specific production of CoQ10 was noted at 10 mg/g dry cell weight (DCW) in media supplemented with 4‐hydroxybenzoic acid (HBA). This makes S. johnsonii a naturally high CoQ10 producer. New methods for extraction and purification of CoQ10 are also discussed, and identification of a closely eluting side product under normal phase isolation is reported.     

Coenzyme Q10 concentration in plasma and blood cells: what about diurnal changes?

Coenzyme Q10 (CoQ10) is used by the body as an endogenous antioxidant and performs essential functions in mitochondrial energy production. The value of CoQ10 as a biomarker for oxidative stress will be severely restricted if there are huge individual daily variations in its concentration. For analysis of diurnal changes in CoQ10 plasma and blood cell concentrations, blood was collected from nine healthy adults (at two- or three-hour intervals for plasma, and three times a day for blood cells). CoQ10 was analysed by HPLC using electrochemical detection and internal standardisation. Daytime variations in CoQ10 concentration in plasma are maintained within narrow limits and show no statistically significant difference (Kruskal-Wallis). However, a drop at night-time (0300 h) is accompanied by a drop in total cholesterol concentration. Remarkable inter-individual differences in blood cell (erythrocytes, platelets, white blood cells) content of CoQ10 occur with only slight intra-individual daily variations. A correlation (Spearman) is found for cholesterol and CoQ10 content in circulation which may be explained by the carrier capacity of blood for this highly lipophilic substance. Moreover, a diurnal change in hepatic HMG-CoA reductase activity may suggest a common diurnal regulation of synthesis of both CoQ10 and cholesterol.     

Changes in mitochondrial and microsomal rat liver coenzyme Q9 and Q10 content induced by dietary fat and endogenous lipid peroxidation

The influence of different kinds of dietary fat (8%) and of endogenous lipid peroxidation with regard to coenzyme Q9 (CoQ9) and coenzyme Q10 (CoQ10) concentrations in mitochondria and microsomes from rat liver has been investigated by means of an HPLC technique. Although the different diet fats used did not produce any effect on microsomes, it was possible to show that each experimental diet differently influenced the mitochondrial levels of CoQ9 and CoQ10. The highest mitochondrial CoQ content was found in case of a diet supplemented with corn oil. An endogenous oxidative stress induced by adriamycin was able to produce a sharp decrease in mitochondrial CoQ9 levels in the rats to which corn oil was administered. The results suggest that dietary fat ought to be considered when studies concerning CoQ mitochondrial levels are carried out.     

Life-long supplementation with a low dosage of coenzyme Q10 in the rat: effects on antioxidant status and DNA damage

Life-long low-dosage supplementation of coenzyme Q(10) (CoQ(10)) is studied in relation to the antioxidant status and DNA damage. Thirty-two male rats were assigned into two experimental groups differing in the supplementation or not with 0.7 mg/kg/day of CoQ(10). Eight rats per group were killed at 6 and 24 months. Plasma retinol, alpha-tocopherol, coenzyme Q, total antioxidant capacity and fatty acids were analysed. DNA strand breaks were studied in peripheral blood lymphocytes. Aging and supplementation led to significantly higher values for CoQ homologues, retinol and alpha-tocopherol. No difference in total antioxidant capacity was detected at 6 months but significantly lower values were found in aged control animals. Similar DNA strand breaks levels were found at 6 months. Aging led to significantly higher DNA strand breaks levels in both groups but animals supplemented with CoQ(10) led to a significantly lower increase in that marker. Aged rats showed significantly higher polyunsaturated fatty acids. This study demonstrates that lifelong intake of a low dosage of CoQ(10) enhances plasma levels of CoQ(9), CoQ(10), alpha-tocopherol and retinol. In addition, CoQ(10) supplementation attenuates the age-related fall in total antioxidant capacity of plasma and the increase in DNA damage in peripheral blood lymphocytes.     

Antioxidant role of cellular reduced coenzyme Q homologs and alpha-tocopherol in free radical-induced injury of hepatocytes isolated from rats fed diets with different vitamin E contents.

Reduced coenzyme Q9 (CoQ9H2) and reduced coenzyme Q10 (CoQ10H2) as well as alpha-tocopherol (alpha-Toc) are known to be potent lipid-soluble antioxidants in mammalian tissues. Reduced coenzyme Q homolog (CoQnH2) appears to show antioxidant activity independent of that of alpha-Toc (Matsura, T., Yamada, K. and Kawasaki, T. (1992) Biochim. Biophys. Acta 1123, 309-315). To further confirm this, we have studied the antioxidant role of cellular CoQnH2 and alpha-Toc using hepatocytes isolated from rats fed diets containing deficient, sufficient, and excess amounts of vitamin E (VE). Cellular damage was induced with a hydrophilic radical initiator, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). The concentration of alpha-Toc in VE-deficient hepatocytes was approximately 1/12 that in VE-sufficient hepatocytes, whereas the concentration of alpha-Toc in VE-excess hepatocytes was approximately 7-fold that in VE-sufficient hepatocytes. The molar ratios of alpha-Toc to CoQnH2 (CoQ9H2 plus CoQ10H2) in VE-deficient, sufficient and excess cells were 0.03, 0.33 and 2, respectively. In the hepatocytes in these three dietary groups, alpha-Toc status had little effect on the concentration of CoQ homologs. These hepatocytes were incubated with 50 mM AAPH for 4 h. The cell viability in all groups of hepatocytes decreased rapidly after 3 h of AAPH treatment, and was associated with the increase of lipid peroxides. The loss of cell viability and the increase of lipid peroxidation in VE-deficient cells were more pronounced than those in the hepatocytes of the other two groups. The endogenous CoQ9H2 content of each group of hepatocytes decreased linearly with a reciprocal increase in oxidized CoQ9 after addition of AAPH, whereas the decrease of endogenous CoQ10H2 in each group during AAPH treatment was much less than that of endogenous CoQ9H2. alpha-Toc in the three VE dietary groups of hepatocytes was also consumed without a time lag after addition of AAPH, and it was not spared by CoQnH2, even in VE-deficient cells where the CoQnH2 concentration was 38-fold that of alpha-Toc. These results indicate that CoQnH2, especially. CoQ9H2, is a lipid-soluble antioxidant, which is as effective as alpha-Toc in rat hepatocytes under the conditions employed in this study, and acts independently of alpha-Toc to inhibit lipid peroxidation.     

Pneumocystis carinii f. sp. carinii synthesizes de novo four homologs of ubiquinone

Ubiquinone, coenzyme Q, plays a pivotal role in electron transport and is a target for chemotherapy against a number of eukaryotic infectious agents, including Pneumocystis carinii. Coenzyme Q10 was previously identified as the major ubiquinone homolog in P. carinii isolated and purified from rat lungs; CoQ9 was also present. In contrast, CoQ9 and CoQ8 (but not CoQ10) were detected in the lungs of uninfected rat controls. These observations suggested that the pathogen synthesizes CoQ10, and perhaps CoQ9 as well. In the present study, CoQ biosynthesis in P. carinii was examined in greater detail. Radiolabeled mevalonate, a precursor of the CoQ polyprenyl chain, was incorporated in vitro into P. carinii ubiquinones. Incorporation of radiolabeled mevalonate into P. carinii CoQ was not enhanced by treating cells with lovastatin, suggesting that the cells did not transport the drug, or that a lovastatin-insensitive pathway for de novo synthesis of isoprenoids may also function in this organism. Radiolabeled precursors of the ring moiety, including shikimic acid, p-hydroxybenzoic acid, and tyrosine were also incorporated into P. carinii CoQ. Unexpectedly, it was found that not only CoQ9 and CoQ10, but also CoQ7, and CoQ8, were metabolically radiolabeled by all the precursors tested, indicating that the organism synthesizes CoQ7, CoQ8, CoQ9, and CoQ10. Metabolic radiolabeling of ubiquinones in rat lung controls was not detected in experiments using either radioactive mevalonate or p-hydroxybenzoate. Thus the incorporations measured using purified P. carinii preparations were due to the enzymes of the organism.     

Clinical implications of the correlation between coenzyme Q10 and vitamin B6 status.

The endogenous biosynthesis of the quinone nucleus of coenzyme Q10 (CoQ10) from tyrosine is dependent on adequate vitamin B6 nutriture. Lowered blood and tissue levels of CoQ10 have been observed in a number of clinical conditions. Many of these clinical conditions are most prevalent among the elderly. Kalen et al. have shown that blood levels of CoQ10 decline with age. Similarly, Kant et al. have shown that indicators of vitamin B6 status also decline with age. Blood samples were collected from 29 patients who were not currently being supplemented with either CoQ10 or vitamin B6. Mean CoQ10 concentrations was 1.1 +/- 0.3 micrograms/ml of blood. Mean specific activities of EGOT was 0.30 +/- 0.13 mumol pyruvate/hr/10(8) erythrocytes and the mean percent saturation of EGOT with PLP was 78.2 +/- 13.9%. Means for all parameters were within normal ranges. Strong positive correlation was found between CoQ10 and the specific activity of EGOT (r = 0.5787, p < 0.001) and between CoQ10 and the percent saturation of EGOT with PLP (r = 0.4174, p < 0.024). Studies are currently in progress to determine the effect of supplementation with vitamin B6 of blood CoQ10 levels. It appears prudent to recommend that patients receiving supplemental CoQ10 be concurrently supplemented with vitamin B6 to provide for better endogenous synthesis of CoQ10 along with the exogenous CoQ10.     

Mitochondrial coenzyme Q content and aging.

The main objective of this study was to determine the nature of the relationship between aging and mitochondrial coenzyme Q (CoQ) content. Mitochondria in the heart, skeletal muscle, kidney and brain of the mouse varied in both the amount of total CoQ (CoQ9 + CoQ10) content as well as in the ratio of the CoQ9 to CoQ10. CoQ content declined with age only in the skeletal muscle. Caloric restriction (CR) resulted in an increase in the amount of CoQ9 in skeletal muscle mitochondria. This effect was partially reversible upon termination of the caloric restriction regimen. Results suggest that a decrease in mitochondrial CoQ content is an integral aspect of aging in skeletal muscle.