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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
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