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AULA 11

Metabolismo do colesterol

a. Lipoprotenas

b. Apoprotenas e interao

c. Circulao e remoo da lipoprotenas

d. Receptor de apoB100 e hipercolesteremia

e. LDL e regulao da sntese de colesterol

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Sistema P-450 e hidroxilao de esteroide

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CH3

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As lipoprotenas e o transporte de colesterol

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Colesterol e lipoprotenas

colesterolVLDL

adipcitos

LP

LP AG

AG

IDL

IDLLDL

LDL

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quilomicrons

Lipoprotenalipase

cidos gordos

Remanescentesde quilomicrons

triglicridos

glucoseGlicerol-3-Pi

glicerol

apoC

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De A. Attie , Dept of Biochemistry , U.Madison

Secreo de VLDL e formao de IDL e LDL

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Modelo de estrutura de uma lipoprotena

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The Nobel Prize in Physiologyor Medicine 1985

for their discoveriesconcerning the regulation ofcholesterol metabolism"

Michael Joseph BrownGoldstein Modelo de

internalizao da LDL

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LDL e RECEPTOR

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Low-Density Lipoprotein ReceptorFragment: Ligand-Binding Domain

1997

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Domain structure of hamster HMG CoA

reductase.

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Model for sterol-regulated Scap-SREBP pathway. SCAP is a sensor of sterols and an escortof SREBPs. In sterol-depleted cells, Scap facilitates export of SREBPs from the ER to the

Golgi apparatus, where two proteases, Site-1 protease (S1P) and Site-2 protease (S2P), act

to release the transcriptionally active, N-terminal bHLH-Zip domain of SREBPs from the

membrane

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Pathway for sterol-accelerated degradation of

HMG CoA reductase.

Feedback regulation of cholesterol synthesis:

sterol-accelerated ubiquitination and

degradation of HMG CoA reductaseRussell A DeBose-Boyd (200

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The SREBP regulatory pathway

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sterol regulatory element-binding

transcription factor 1

TCACNCCAC

Sequencia na regio promotora a que se

liga o SRBP

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intramembrane cholesterol regulates its own synthesis in mammalian cells. Sterolregulatory element-binding proteins (SREBPs), membrane-embedded

transcriptional activators of cholesterol synthesis, are transported by Scap to the

Golgi complex in COPII-coated vesicles for processing.

Sun et al., (2005) JBC pages 2648326490.

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Julio Pomar