Über das Vorkommen von Dihydroxysterinen im menschlichen Gehirn

Schubert, Kurt; Rose, G.; Burger, Max M.

doi:10.1515/bchm2.1961.326.1.235

Cited by 16 publications

(6 citation statements)

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“…This oxysterol was subsequently detected in the human (23–26), bovine (26, 27), rabbit (26), and rat brain (28) at levels of tens of micrograms per gram of tissue and was shown to consist of a single epimer, 24 S -hydroxycholesterol (21). Smith and colleagues in Galveston, Texas, showed that microsomes from bovine brain (26) and rat brain (28) converted cholesterol into 24 S -hydroxycholesterol in a reaction requiring NADPH, and they speculated that the enzyme involved was a cytochrome P450 (P450).…”

Section: S-hydroxycholesterol and Cholesterol Turnovermentioning

confidence: 99%

Cholesterol 24-Hydroxylase: An Enzyme of Cholesterol Turnover in the Brain

Russell

Halford

Ramirez

et al. 2009

Annu. Rev. Biochem.

263

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Cholesterol 24-hydroxylase is a highly conserved cytochrome P450 that is responsible for the majority of cholesterol turnover in the vertebrate central nervous system. The enzyme is expressed in neurons, including hippocampal and cortical neurons that are important for learning and memory formation. Disruption of the cholesterol 24-hydroxylase gene in the mouse reduces both cholesterol turnover and synthesis in the brain but does not alter steady-state levels of cholesterol in the tissue. The decline in synthesis reduces the flow of metabolites through the cholesterol biosynthetic pathway, of which one, geranylgeraniol diphosphate, is required for learning in the whole animal and for synaptic plasticity in vitro. This review focuses on how the link between cholesterol metabolism and higher-order brain function was experimentally established.

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Section: S-hydroxycholesterol and Cholesterol Turnovermentioning

confidence: 99%

Cholesterol 24-Hydroxylase: An Enzyme of Cholesterol Turnover in the Brain

Russell

Halford

Ramirez

et al. 2009

Annu. Rev. Biochem.

263

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show abstract

“…Many oxysterols found in living organisms are also present in air‐aged cholesterol, which led to the speculation that some of them may have fundamental roles in mammalian cells 8. Although secondary autoxidation products have been detected in cholesterol‐rich human tissues, the 24‐hydroxycholesterol in human brain9 and 27(26)‐hydroxycholesterol in human atherosclerotic plaques10 are mainly of enzymatic origin. Most oxysterols found in nature are derived from singlet‐oxygen attack at the cholesterol Δ5 double bond to give the 5‐ and 7‐hydroperoxide derivatives and their decomposition products 11.…”

Section: Methodsmentioning

confidence: 99%

“…[8] Although secondary autoxidation products have been detected in cholesterol-rich human tissues, 24-hydroxycholesterol in human brain [9] and 27(26)-hydroxycholesterol in human atherosclerotic plaques [10] are mainly of enzymatic origin. Most oxysterols found in nature are derived from singlet oxygen attack at the cholesterol Δ5 double bond to give the 5- and 7-hydroperoxide derivatives and their decomposition products.…”

mentioning

confidence: 99%

Cholesterol Hydroperoxides as Substrates for Cholesterol‐Metabolizing Cytochrome P450 Enzymes and Alternative Sources of 25‐Hydroxycholesterol and other Oxysterols

Lier

Mast²,

Pikuleva

2015

Angew Chem Int Ed

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The interaction of primary autoxidation products of cholesterol, 25- and 20ξ-hydroperoxides, with the four principal cholesterol-metabolizing cytochrome P450 enzymes is reported. Addition of cholesterol 25-hydroperoxide to CYP27A1 and CYP11A1 induced well-defined spectral changes while generating 25-hydroxycholesterol as major product along with small amounts of triols. The 20ξ-hydroperoxides induced spectral shifts in CYP27A1 and CYP11A1, yet glycol metabolites were detected only with CYP11A1. CYP7A1 and CYP46A1 failed to give metabolites with any of the hydroperoxides. A P450 hydroperoxide-shunt reaction is proposed, where the hydroperoxides serve both as donor for reduced oxygen and as substrate. For the first time, CYP27A1 is shown to mediate the reduction of cholesterol 25-hydroperoxide to 25-hydroxycholesterol, a role of potential significance for cholesterol-rich tissues with high oxidative stress. CYP27A1 may participate in these tissues in removal of harmful autoxidation products, while providing a complementary source for 25-hydroxycholesterol, a modulator of immune cell function and mediator of viral cell entry.

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“…[8] Although secondary autoxidation products have been detected in cholesterol-rich human tissues,t he 24-hydroxycholesterol in human brain [9] and 27(26)-hydroxycholesterol in human atherosclerotic plaques [10] are mainly of enzymatic origin. [8] Although secondary autoxidation products have been detected in cholesterol-rich human tissues,t he 24-hydroxycholesterol in human brain [9] and 27(26)-hydroxycholesterol in human atherosclerotic plaques [10] are mainly of enzymatic origin.…”

mentioning

confidence: 99%

“…Many oxysterols found in living organisms are also present in air-aged cholesterol, which led to the speculation that some of them may have fundamental roles in mammalian cells. [8] Although secondary autoxidation products have been detected in cholesterol-rich human tissues,t he 24-hydroxycholesterol in human brain [9] and 27(26)-hydroxycholesterol in human atherosclerotic plaques [10] are mainly of enzymatic origin. Most oxysterols found in nature are derived from singlet-oxygen attack at the cholesterol D5d ouble bond to give the 5-and 7-hydroperoxide derivatives and their decomposition products.…”

mentioning

confidence: 99%

Cholesterol Hydroperoxides as Substrates for Cholesterol‐Metabolizing Cytochrome P450 Enzymes and Alternative Sources of 25‐Hydroxycholesterol and other Oxysterols

Lier

Mast²,

Pikuleva

2015

Angewandte Chemie

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The interaction of the primary autoxidation products of cholesterol, namely 25-and 20x-hydroperoxides,w ith the four principal cholesterol-metabolizing cytochrome P450 enzymes is reported. Addition of cholesterol 25-hydroperoxide to the enzymes CYP27A1 and CYP11A1 induced well-defined spectral changes while generating 25-hydroxycholesterol as the major product. The 20x-hydroperoxides induced spectral shifts in CYP27A1 and CYP11A1 but glycol metabolites were detected only with CYP11A1. CYP7A1 and CYP46A1 failed to give metabolites with any of the hydroperoxides.AP450 hydroperoxide-shunt reaction is proposed, where the hydroperoxides serve as both donor for reduced oxygen and substrate.C YP27A1 was shown to mediate the reduction of cholesterol 25-hydroperoxide to 25-hydroxycholesterol, ar ole of potential significance for cholesterol-richt issues with high oxidative stress.C YP27A1 may participate in the removal of harmful autoxidation products in these tissues,while providing ac omplementary source of 25-hydroxycholesterol, am odulator of immune cell function and mediator of viral cell entry.

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Über das Vorkommen von Dihydroxysterinen im menschlichen Gehirn

Cited by 16 publications

References 0 publications

Cholesterol 24-Hydroxylase: An Enzyme of Cholesterol Turnover in the Brain

Cholesterol 24-Hydroxylase: An Enzyme of Cholesterol Turnover in the Brain

Cholesterol Hydroperoxides as Substrates for Cholesterol‐Metabolizing Cytochrome P450 Enzymes and Alternative Sources of 25‐Hydroxycholesterol and other Oxysterols

Cholesterol Hydroperoxides as Substrates for Cholesterol‐Metabolizing Cytochrome P450 Enzymes and Alternative Sources of 25‐Hydroxycholesterol and other Oxysterols

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