Metabolism of ubiquinone in relation to thyroxine status

Inamdar, A.R.; Ramasarma, T.

doi:10.1042/bj1110479

Cited by 11 publications

(4 citation statements)

References 20 publications

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“…Some information is available regarding the effects of thyroid hormone on vitamin E and Coenzyme Q, present at relatively high concentrations in the inner mitochondrial membrane, where they reduce free radical-initiated lipid peroxidation [162,163]. Early studies showed that hyperthyroidism increases the content of ubiquinone [97,164], but does not modify vitamin E content in liver mitochondria [12]. More recently, the increase in ubiquinone content and lack of changes in vitamin E content, besides being confirmed in the liver, has also been shown in cardiac and skeletal muscle from hyperthyroid rats [96].…”

Section: Mitochondrial Oxidative Damage and The Antioxidant Defence Smentioning

confidence: 98%

Thyroid hormone-induced oxidative stress

Venditti

Meo

2006

Cell. Mol. Life Sci.

336

230

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Hypermetabolic state in hyperthyroidism is associated with tissue oxidative injury. Available data indicate that hyperthyroid tissues exhibit an increased ROS and RNS production. The increased mitochondrial ROS generation is a side effect of the enhanced level of electron carriers, by which hyperthyroid tissues increase their metabolic capacity. Investigations of antioxidant defence system have returned controversial results. Moreover, other thyroid hormone-linked biochemical changes increase tissue susceptibility to oxidative challenge, which exacerbates the injury and dysfunction they suffer under stressful conditions. Mitochondria, as a primary target for oxidative stress, might account for hyperthyroidism linked tissue dysfunction. This is consistent with the inverse relationship found between functional recovery of ischemic hyperthyroid hearts and mitochondrial oxidative damage and respiration impairment. However, thyroid hormone-activated mitochondrial mechanisms provide protection against excessive tissue dysfunction, including increased expression of uncoupling proteins, proteolytic enzymes and transcriptional coactivator PGC-1, and stimulate opening of permeability transition pores.

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Section: Mitochondrial Oxidative Damage and The Antioxidant Defence Smentioning

confidence: 98%

Thyroid hormone-induced oxidative stress

Venditti

Meo

2006

Cell. Mol. Life Sci.

336

230

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“…In rat liver, the occurrence of CoQ10 is about 175 nmol/g fresh tissue [49]. However, coenzyme Q levels are substantially depleted in the liver of a starved animal and could be too low to be detected in such a case [50]. Therefore, the effect of the endogenous CoQ 10 on the finding of this study was likely to be negligible, as the liver microsomes used were prepared from the fasted rats.…”

Section: Discussionmentioning

confidence: 94%

Effect of Coenzyme Q10 on Warfarin Hydroxylation in Rat and Human Liver Microsomes

Zhou¹,

Zhou²,

Chan

2005

CDM

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Our previous animal study has suggested that the accelerated metabolism of warfarin enantiomers with concurrent coenzyme Q(10) (CoQ(10)) treatment accounts for the reduced anticoagulant effect of warfarin in rats. The present study was to assess the effect of CoQ(310) on individual hydroxylation pathways of the in vitro microsomal metabolism of warfarin enantiomers and to extrapolate in vitro data to in vivo situation. The effect of the antioxidant CoQ(10) on the hydroxylation of warfarin enantiomers was examined using rat and human liver microsomes. Based on the in vitro kinetic data, together with the information retrieved from the literature, the magnitude of warfarin-CoQ(10) interaction in man was quantitatively predicted. In rat liver microsomes, CoQ(10) exhibited a selective activation effect on the 4'-hydroxylation of S-warfarin, with a K(A) value (i.e. dissociation constant of the enzyme-activator complex) being one third and one fifth of those for the 6- and 7-hydroxylation, respectively. The activation effect of CoQ(10) was selective towards the 6- and 7-hydroxylation of R-warfarin at low substrate concentrations, but towards the 4'-hydoxylation of the R-enantiomer at high substrate concentrations. In human liver microsomes, CoQ(10) was a selective activator of the 7-hydroxylation of both R- and S-enantiomers of warfarin, with K(A) values being half to one twelfth of those for the other pathways. A relatively accurate prediction was made for the increase in the total and hepatic clearance of both S- and R-warfarin in rats with concurrent CoQ(10) treatment based on their respective overall hydroxylation, when the active transport of CoQ(10)into the hepatocytes was taken into consideration. In man, one would expect about 32% and 17% increase in the total clearance of S- and R-warfarin, respectively, with coadministration of 100 mg CoQ(10). In both species, CoQ(10) had enzyme activation effect, which appeared to be regioselective but not stereoselective, on the formation of the phenolic metabolites of warfarin enantiomers. A moderate increase in the total clearance of warfarin enantiomers could occur with coadministration of CoQ(10)in humans.

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“…Our results for the serum substrate revealed that the primary disturbed statistically significant pathways (p < 0.05), in response to hypothyroidism, were aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism and ubiquinone and other terpenoid-quinone biosyntheses (Table S3). The relationship between the ubiquinone metabolism and thyroxine status has been reported since the late 1960s, with higher levels of thyroxine leading to higher ubiquinone concentrations and accumulations in the liver due to an increased biosynthesis and to a partly decreased catabolism [56]. Specifically, the pathways of importance containing at least two compounds involve phenylalanine, tyrosine and tryptophan biosynthesis, aminoacyl-tRNA biosynthesis and the phenylalanine metabolism.…”

Section: Metabolitepathway Analysismentioning

confidence: 99%

Uncontrolled Thyroid during Pregnancy Alters the Circulative and Exerted Metabolome

Fotakis

Moros

Kontogeorgou

et al. 2022

IJMS

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Normal levels of thyroid hormones (THs) are essential for a normal pregnancy outcome, fetal growth and the normal function of the central nervous system. Hypothyroidism, a common endocrine disorder during pregnancy, is a significant metabolic factor leading to cognitive impairments. It is essential to investigate whether patients with thyroid dysfunction may present an altered circulative and excreted metabolic profile, even after receiving treatment with thyroxine supplements. NMR metabolomics was employed to analyze 90 serum and corresponding colostrum samples. Parallel analyses of the two biological specimens provided a snapshot of the maternal metabolism through the excretive and circulating characteristics of mothers. The metabolomics data were analyzed by performing multivariate statistical, biomarker and pathway analyses. Our results highlight the impact of hypothyroidism on metabolites’ composition during pregnancy and lactation. Thyroid disorder causing metabolite fluctuations may lead to impaired lipid and glucose metabolic pathways as well as aberrant prenatal neurodevelopment, thus posing a background for the occurrence of metabolic syndrome or neurogenerative diseases later in life. This risk applies to not only untreated but also hypothyroid women under replacement therapy since our findings in both biofluids framed a different metabolic phenotype for the latter group, thus emphasizing the need to monitor women adequately after treatment initiation.

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Metabolism of ubiquinone in relation to thyroxine status

Cited by 11 publications

References 20 publications

Thyroid hormone-induced oxidative stress

Thyroid hormone-induced oxidative stress

Effect of Coenzyme Q10 on Warfarin Hydroxylation in Rat and Human Liver Microsomes

Uncontrolled Thyroid during Pregnancy Alters the Circulative and Exerted Metabolome

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