Regulation of the mevalonate pathway

Goldstein, Joseph L.; Brown, Michael S.

doi:10.1038/343425a0

Cited by 4,922 publications

(3,520 citation statements)

References 82 publications

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“…HMG-CoA reductase is the rate-limiting enzyme in the cholesterol biosynthetic pathway. The inhibition of HMGCoA reductase decreases cholesterol synthesis and is very effective in lowering plasma cholesterol (Goldstein and Brown 1990). High cholesterol diet itself inhibited HMGCoA reductase activity in our study for the feedback regulation of cholesterol, which was also illustrated by Hayashi et al (2004).…”

Section: Resultssupporting

confidence: 65%

Hypocholesterolemic effects of Auricularia auricula ethanol extract in ICR mice fed a cholesterol-enriched diet

Gang

Luo

et al. 2010

J Food Sci Technol

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The cholesterol-lowering properties of Auricularia auricula are commonly attributed to the presence of polysaccharides based on previous research. The present study was designed to investigate the effects of ethanol extract of A. auricula (AAE) on hypercholesterolemia in ICR mice. AAE contained more than 16% (g/g) polyphenolic compounds, excluding other interfering factors such as polysaccharides, water-soluble fibre and protein. Thirtysix mice were randomly assigned to three groups (n=12). The experimental group was fed cholesterol-enriched diet (CED) with oral administration of AAE (150 mg/kg/d b.w.) for 8-week, normal control group and CED control group received either a regular diet (RD) or CED along with oral administration of equal volume distilled water. Serum lipid profiles and antioxidant status were measured in addition to fecal neutral cholesterol and bile acids. AAE showed a remarkable hypocholesterolemic effect, improving antioxidant status, decreasing the level of total cholesterol and atherosclerosis index, increasing the level of high-density lipoprotein cholesterol and fecal excretion of bile acids. No apparent effects on serum triglycerides, low-density lipoprotein cholesterol, fecal excretion of neutral cholesterol and feeding efficiency were observed among all groups. These results indicated that A. auricula functional components, which prevented hypercholesterolemia contained polyphenolic compounds, in addition to polysaccharides.

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Section: Resultssupporting

confidence: 65%

Hypocholesterolemic effects of Auricularia auricula ethanol extract in ICR mice fed a cholesterol-enriched diet

Gang

Luo

et al. 2010

J Food Sci Technol

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“…HMGCoAR is the rate-limiting enzyme of cholesterol synthesis, yet surprisingly, low cholesterol levels provide only a relatively weak feedback effect on HMGCoAR. 34 HMGCoAR is under highly complex regulation, 35 but a critical regulator is feedback through the direct sterol-sensing of the lanosterol level (Fig. 1).…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C virus selectively perturbs the distal cholesterol synthesis pathway in a genotype-specific manner

et al. 2012

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Hepatitis C virus (HCV) subverts host cholesterol metabolism for key processes in its lifecycle. How this interference results in the frequently observed, genotype-dependent clinical sequelae of hypocholesterolemia, hepatic steatosis, and insulin resistance (IR) remains incompletely understood. Hypocholesterolemia typically resolves after sustained viral response (SVR), implicating viral interference in host lipid metabolism. Using a targeted cholesterol metabolomic platform we evaluated paired HCV genotype 2 (G2) and G3 patient sera for changes in in vivo HCV sterol pathway metabolites. We compared HCV genotypic differences in baseline metabolites and following antiviral treatment to assess whether sterol perturbation resolved after HCV eradication. We linked these metabolites to IR and urine oxidative stress markers. In paired sera from HCV G2 (n 5 13) and G3 (n 5 20) patients, baseline sterol levels were lower in G3 than G2 for distal metabolites (7-dehyrocholesterol (7DHC) 0.017 versus 0.023 mg/dL; P adj 5 0.0524, cholesterol 140.9 versus 178.7 mg/dL; P adj 5 0.0242) but not the proximal metabolite lanosterol. In HCV G3, SVR resulted in increased levels of distal metabolites (cholesterol [D55.2 mg/dL; P adj 5 0.0015], 7DHC [D0.0075 mg/dL; P adj 5 0.0026], lathosterol [D0.0430 mg/dL P adj 5 0.0405]). In contrast, lanosterol was unchanged after SVR (P 5 0.9515). Conclusion: HCV G3, but not G2, selectively interferes with the late cholesterol synthesis pathway, evidenced by lower distal sterol metabolites and preserved lanosterol levels. This distal interference resolves with SVR. Normal lanosterol levels provide a signal for the continued proteolysis of 3-hydroxyl-3-methylglutaryl coenzyme A reductase, which may undermine other host responses to increase cholesterol synthesis. These data may provide a hypothesis to explain why hypocholesterolemia persists in chronic HCV infection, particularly in HCV G3, and is not overcome by host cholesterol compensatory mechanisms. (HEPATOLOGY 2012;56:49-56)

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“…In neither Vero fibroblasts nor hepatoma cells could a direct inhibition of HMGR be found. Therefore the suppression of the up-regulation of HMGR that occurs when the cells are grown in LDM [24] could be caused by the interference of policosanol with the regulation of HMGR. One of the mechanisms of negative regulation of HMGR is the phosphorylation by the AMP kinase (AMPK) [25].…”

Section: Introductionmentioning

confidence: 99%

Regulation of HMGCoA Reductase Activity by Policosanol and Octacosadienol, a New Synthetic Analogue of Octacosanol

Oliaro‐Bosso

Gaudino

Mantegna

et al. 2009

Lipids

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Regulation of the mevalonate pathway

Cited by 4,922 publications

References 82 publications

Hypocholesterolemic effects of Auricularia auricula ethanol extract in ICR mice fed a cholesterol-enriched diet

Hypocholesterolemic effects of Auricularia auricula ethanol extract in ICR mice fed a cholesterol-enriched diet

Hepatitis C virus selectively perturbs the distal cholesterol synthesis pathway in a genotype-specific manner

Regulation of HMGCoA Reductase Activity by Policosanol and Octacosadienol, a New Synthetic Analogue of Octacosanol

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