Physiological and pharmacological regulation of small intestinal cholesterol synthesis

Strandberg, Timo; Tilvis, R.S.

doi:10.1016/0306-3623(88)90024-9

Cited by 8 publications

(2 citation statements)

References 75 publications

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“…The cascade ends with reduction of 7‐dehydrocholesterol that is catalyzed by 7‐dehydrocholesterol reductase (Dhcr7; EC 1.3.1.21) enzyme (Bae et al,1999). Liver and small intestine are the major sites of cholesterol biosynthesis for the whole body (Strandberg and Tilvis,1988). However, all of the brain cholesterol is synthesized locally, with the highest rate of synthesis occurring during first postnatal weeks in humans and rodents (Jurevics and Morell,1995; Jurevics et al,1997).…”

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Molecular consequences of altered neuronal cholesterol biosynthesis

Korade¹,

Kenworthy²,

Mirnics³

2008

J of Neuroscience Research

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The first dedicated step in de novo cholesterol biosynthesis begins with formation of squalene and ends with the reduction of 7-dehydrocholesterol by 7-dehydrocholesterol reductase (Dhcr7) into cholesterol, which is an essential structural and signaling molecule. Mutations in the Dhcr7 gene lead to Smith-Lemli-Opitz syndrome (SLOS), which is characterized by developmental deformities, incomplete myelination, and mental retardation. To understand better the molecular consequences of Dhcr7 deficiency in neuronal tissue, we analyzed the effect of cholesterol deficiency on the transcriptome in Neuro2a cells. Transient down-regulation of Dhcr7 by siRNA led to altered expression of multiple molecules that play critical roles in intracellular signaling or vesicular transport or are inserted into membrane rafts (e.g. Egr1, Snx, and Adam19). A similar down-regulation was also observed in stable Dhrc7-shRNA-transfected cell lines, and the findings were verified by qPCR. Furthermore, we investigated the Dhcr7-deficient and control cells for the expression of several critical genes involved in lipid biosynthesis. Among these, fatty acid synthase, sterol-regulatory element binding protein 2, SREBF chaperone, site-1 protease, and squalene synthase showed a significant down-regulation, suggesting that, in a neuronal cell line, Dhcr7 is a potent regulator of lipid biosynthesis. Importantly, the gene expression changes were present in both lipid-containing and cholesterol-deficient media, suggesting that intrinsic cholesterol biosynthesis is necessary for normal neuronal function and cannot be supplemented from extrinsic sources.

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confidence: 99%

Molecular consequences of altered neuronal cholesterol biosynthesis

Korade¹,

Kenworthy²,

Mirnics³

2008

J of Neuroscience Research

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“…A terceira reação é o passo decisivo, sem retorno, onde ocorre a redução do HMG-CoA em mevalonato, para o qual duas moléculas de NADPH doam cada uma delas dois elétrons, sendo esta etapa catalisada pela HMG-CoA redutase(DAVID;COX, 2006). A semelhança dos outros órgãos, esta transformação do HMG-CoA a mevalonato é a etapa limitante da síntese de colesterol(STRANDBERG;TILVIS, 1988). Na segunda etapa ocorre a conversão do mevalonato em duas unidades de isopreno ativado, onde três grupos fosfatos são transferidos de três moléculas de ATP para o mevalonato.…”

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Efeitos de dois níveis de sulfato de cobre e cobre metionina no metabolismo e oxidação de lipídios em ovinos

Garrine¹

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Antioxidantes 2. Colesterol 3. Enzimas 4. Minerais. I. Título. 12 months for study of oxidative stability. After that, steaks of m. longissimus were collected and exposed to "display life" (DL) (4°C) to study oxidative stability which was accompanied by TBARS values on days 0, 3 and 6. The copper supplementation resulted in higher concentration and accumulation of Cu in the liver (P<0.05), however, the concentration of Cu in muscle was not altered by supplementation (P>0.05). There was no significant effect (P>0.05) for fat thickness, serum triglycerides, total cholesterol, HDL and LDL between control and copper supplementation regardless of the source. The copper supplementation altered the fatty acid profile of the meat (P<0.05), with an increase in the proportion of lauric acid (C12: 0) in the control group compared with the other treatments (P<0.05). Copper supplementation reduced cholesterol concentration in m. longissimus (P<0.05) in supplemented lambs compared to the control group, this reduction was accompanied by reduction concentrations of GSH (P<0.05) and increasing of oxidized glutathione (GSSG) in the liver (P<0.05). There was no effect of Cu supplementation for TBARS in the liver however, there was significant effect on m. longissimus collected during sawing (P<0.10). There was no effect of Cu supplementation for TBARS in the m. longissimus exposed in the "Display Life after 12 months vacuum freezing (P>0.05), but there was a linear increase in TBARS values during this period. Cu supplementation increased the activity of SOD and GP-x (P<0.05) in the liver. These results suggest that copper can be used to improve meat quality without affecting the oxidative stability.

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