15 - zemin yao professor and chair biochemistry,...

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Unformatted text preview: zemin yao professor and chair biochemistry, microbiology & immunology e-mail: zyao@uottawa.ca 03-07-11, Mon. 10:00-11:30 10:00-11:30 am BCH 3120 lipid and amino acid metabolism 02-09-11, Wed fatty acid oxidation 02-14-11, Mon ketogenesis and fatty acid synthesis 02-16-11, Wed triacylglycerol and phospholipid synthesis uOttawa reading break 02-28-11, Mon biosynthesis of cholesterol 03-02-11, Wed lipoprotein metabolism 03-07-11, Mon regulation of cholesterol homeostasis 03-09-11, Wed amino acid deamination and the urea cycle 03-14-11, Mon biosynthesis of amino acids and related molecules 03-16-11, Wed regulation of amino acid metabolism 03-21-11, Mon midterm course outline cholesterol homeostasis cholesterol de novo synthesis cell taken up from outside of cells excretion as bile acids cholesteryl ester 1. HMG-CoA reductase 1 2. ACAT 2 efflux 5 5. HDL cycle 3. LDL receptor 3 4 4. bile acid todays lecture regulation of the mevalonate pathway regulation of the LDL receptor pathway the SREBP/SCAP/INSIG axis regulation of HMG-CoA reductase post-translational regulation phosphorylation degradation transcriptional regulation N-terminal transmembrane domain of HMG-CoA reductase acts as a cholesterol sensor cytoplasm ER lumen N C cholesterol degradation cholesterol sensing domain regulation of HMG-CoA reductase post-translational regulation phosphorylation degradation transcriptional regulation transcription regulation of gene expression SRE trans element HMG-CoA reductase-350-300-250-200-150-100-50 +1 transcription start promoter region cis element SREBP transcription regulation of the HMG-CoA reductase gene the promoter region of the HMG-CoA reductase gene contains a cis element termed SRE (sterol-regulatory element or sterol-responsive element) binding of the trans element SREBP (SRE binding protein) to SRE activates transcription of HMG-CoA reductase availability of SREBP is governed by cholesterol concentrations within the cells SRE HMG-CoA reductase-350-300-250-200-150-100-50 +1 SREBP regulation of HMG-CoA reductase expression by cholesterol SRE [cholesterol] low SREBP [cholesterol] high low concentration of cholesterol results in high level of SREBP cholesterol de novo synthesis cell receptor-mediated cholesterol uptake excretion as bile acids cholesteryl ester 1. HMG-CoA reductase 1 2. ACAT 2 efflux 3. LDL receptor 3 SREBP SREBP todays lecture regulation of the mevalonate pathway regulation of the LDL receptor pathway the SREBP/SCAP/INSIG axis LDLR we have learned two receptors that are involved in cholesterol uptake LDL endocytosis SR-B1 apoA-I cholesterol selective uptake apoB100 HDL cell promoters of genes regulating cholesterol metabolism contain SRE SRE HMG-CoA reductase-350-300-250-200-150-100-50 +1 LDL receptor SRE HMG-CoA synthase SRE SRE SRE SREBP SREBP SREBP SREBP SREBP what is SREBP?what is SREBP?...
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15 - zemin yao professor and chair biochemistry,...

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