| 1. |
- Bentinger, Magnus, et al.
(författare)
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Coenzyme Q - Biosynthesis and functions
- 2010
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 396:1, s. 74-79
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Tidskriftsartikel (refereegranskat)abstract
- In addition to its role as a component of the mitochondrial respiratory chain and our only lipid-soluble antioxidant synthesized endogenously, in recent years coenzyme Q (CoQ) has been found to have an increasing number of other important functions required for normal metabolic processes. A number of genetic mutations that reduce CoQ biosynthesis are associated with serious functional disturbances that can be eliminated by dietary administration of this lipid, making CoQ deficiencies the only mitochondrial diseases which can be successfully treated at present. In connection with certain other diseases associated with excessive oxidative stress, the level of CoQ is elevated as a protective response. Aging, certain experimental conditions and several human diseases reduce this level, resulting in serious metabolic disturbances. Since dietary uptake of this lipid is limited, up-regulation of its biosynthetic pathway is of considerable clinical interest. One approach for this purpose is administration of epoxidated all-trans polyisoprenoids, which enhance both CoQ biosynthesis and levels in experimental systems.
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| 2. |
- Bentinger, Magnus, et al.
(författare)
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Effects of various squalene epoxides on coenzyme Q and cholesterol synthesis
- 2014
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Ingår i: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. - : Elsevier BV. - 1388-1981 .- 1879-2618. ; 1841:7, s. 977-986
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Tidskriftsartikel (refereegranskat)abstract
- 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 [H-3]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.
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| 3. |
- Bentinger, Magnus, et al.
(författare)
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Influence of liver-X-receptor on tissue cholesterol, coenzyme Q and dolichol content
- 2012
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Ingår i: Molecular membrane biology. - : Informa UK Limited. - 0968-7688 .- 1464-5203. ; 29:7, s. 299-308
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Tidskriftsartikel (refereegranskat)abstract
- The organ content of the mevalonate pathway lipids was investigated in liver-X-receptor (LXR) alpha, beta and double knockout mice. An extensive or moderate increase of total cholesterol in the double KO mice was found in all organs elicited by the increase of the esterified form. In LXR alpha and double KO mice, coenzyme Q (CoQ) was decreased in liver and increased in spleen, thymus and lung, while dolichol was increased in all organs investigated. This effect was confirmed using LXR-agonist GW 3965. Analysis of CoQ distribution in organelles showed that the modifications are present in all cellular compartments and that the increase of the lipid in mitochondria was the result of a net increase of CoQ without changing the number of mitochondria. It appears that LXR influences not only cellular cholesterol homeostasis but also the metabolism of CoQ and dolichol, in an indirect manner.
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| 4. |
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| 5. |
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| 6. |
- Bentinger, Magnus, et al.
(författare)
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Stimulation of coenzyme Q synthesis.
- 2008
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Ingår i: Biofactors. - : Wiley. - 0951-6433 .- 1872-8081. ; 32:1-4, s. 99-111
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Tidskriftsartikel (refereegranskat)
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| 7. |
- Surmacz, Liliana, et al.
(författare)
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Short-chain polyisoprenoids in the yeast Saccharomyces cerevisiae - New companions of the old guys
- 2015
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Ingår i: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. - : Elsevier BV. - 1388-1981 .- 1879-2618. ; 1851:10, s. 1296-1303
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Tidskriftsartikel (refereegranskat)abstract
- Dolichols are, among others, obligatory cofactors of protein glycosylation in eukaryotic cells. It is well known that yeast cells accumulate a family of dolichols with Dol-15/16 dominating while upon certain physiological conditions a second family with Dol-21 dominating is noted. In this report we identified the presence of additional short-chain length polyprenols - all-trans Pren-7 in three yeast strains (SS328, BY4741 and L5366), Pren-7 was accompanied by traces of putative Pren-6 and -8. Moreover, in two of these strains a single polyprenol mainly-cis-Pren-11 was synthesized at the stationary phase of growth. Identity of polyprenols was confirmed by HR-HPLC/MS, NMR and metabolic labeling. Additionally, simvastatin inhibited their biosynthesis.
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