Cholesterol Metabolism, Ldl, and the Ldl Receptor by N. B. Myant

By N. B. Myant

Ldl cholesterol Metabolism, LDL, and the LDL Receptor

summary: ldl cholesterol Metabolism, LDL, and the LDL Receptor

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N ean dactivit yo fhybri dgene sconstructe dfro mvariou sportion so fth epromote rregio no fth ereductas egen ejoine dt oth e 7— 4 28 pRed CA T - 7 5. 0 042 pRedCA T- 9 5. (Fro mOsborn ee ta/. ,1985 ,wit hth epermissio no fth eauthors. Structur 7 81 pRed CAT- 21 pRed CAT- 12 8 61 0 75 pRed CAT- 310 R e l a t i v e Percen Promoter Suppressio Plasmid A c t i v i t yb y Sterol s 44 3. H M G - C o A Reductas e Since plasmi dpSVO-CATha s n o eukaryotic promote rsequences , expressio n of CA Ti ntransfectedcell s provide da ninde xo f promote ractivit yi nth e reduc tase-gene sequence s presen ti nth e constructs .

1983) . Thes e worker s hav e describe dexperiment s whic hsugges t thatLD Linhibit s reductas ei ncell si ncultur eb y partia l inhibitio no f oxidos qualene cyclase , leadin g t o th e accumulationo f squalen e dioxid e which ,i nturn , is cyclize dt ofor minhibitor y oxysterols . Whilei tha s no tbee nestablishe dtha toxygenate dprecursorso f cholestero l ar e physiological regulatorso f HMG-Co A reductase , tw o line so f evidenc e strongl y suggesttha tinhibitio no f reductase b y endogenou san dexogenou s cholestero li s mediatedb y oxystero l generate denzymicall yfro mcholestero l withi ncells .

Thes edifference s ma y b e explaine di nterm so f the multivalen tcontro lo f reductase discusse da s follows . HDL , b y withdrawin g cholesterolfro mcells , release s reductas e synthesi sfro mth e norma l repressio n exertedb y cholestero l o rothe rstero l presen ti nth e regulatory poo l (Fig . 11) , whereas compacti nreverse s repressio nexerte db ya nonstero l derivativ eo f mevalonicaci da s wel la s tha tdu e t o cholestero l synthesize db y th e cell . Inmos tcases , change si nreductas e synthesi s brough tabou tb y sterol s ar e mediatedb y change si nth e rat eo f transcriptiono f th e reductas e gene .

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