Textbook and Required Readings (Midterm) Flashcards
What are the three principal lipid components of bile?
Bile salts, pancreatic lipase, and sterols
Which fatty acids are resistant to hydrolysis by lipase?
FAs linked at the sn-2 position of MGs, PLs, and CEs
Under what form is cholesterol present in bile?
Unesterified form
Where is biliary cholesterol absorbed?
At a site more proximal than diet-derived cholesterol within the small intestine
What are the hydrophilic components in lipoproteins?
Phospholipid polar head groups and cholesterol hydroxyl groups
What forms the core of lipoprotein molecules?
Hydrophobic cholesterol esters and triglycerides
What does the exogenous transport system transfer?
Transfers lipids of intestinal origin to peripheral and hepatic tissues
What is the relation between MTP and Apo-B?
MTP transfers lipids onto nascent Apo-B particles to create chylomicrons
What do chylomicron TG-depleted remnant particles take up? Where are they taken?
- Take up CE from HDLs
- Rapidly taken up by the liver
What is the function of ABCA1?
Mediate the efflux of cellular cholesterol and phospholipids to lipid-poor HDL
Where is Apo E synthesized? Where is it present?
- In the liver
- On all forms of lipoproteins
Why is Apo E important?
In the hepatic clearance of TG-depleted chylomicron remnants
Where is LDL cleared from the plasma?
- Liver
- Adipocytes
- Smooth muscle cells
- Fibroblasts
- All contain the LDLR
As HDL becomes enriched with CE, ______ and ______ are picked up from other proteins to form spherical HDL.
Apo-C-II and Apo-C-III
What does CETP exchange?
- CE from HDL2 to VLDL and CM
- TG from VLDL and CM to HDL2
As a result of CETP’s action, what does HDL2 convert to?
Reconverts to HDL3
What is the consequence of manipulating ER calcium?
- Causes the re-distribution of a portion of intracellular UC to a pool that is NOT available to the SCAP-SREBP complex
- Not directly accessible to the components of the cholesterol-sensing mechanism
What kind of nuclear receptors are steroid receptors?
Homodimers
What kind of nuclear receptors are RXR receptors?
Heterodimer
How do co-regulators influence transcription?
Through chromatin remodeling with histone modifications
What is the consequence of increased function of LXR?
Decreases cholesterol from the GI tract
What are the two properties of the LDL receptor?
- Allows large amounts of cholesterol to be delivered to the body
- Keeps concentration of LDL in the blood low enough to avoid buildup (plaques)
What is the second messenger responsible for suppressing HMGR activity?
Cholesterol generated from LDL within the lysosome
What lipoproteins does LDLR bind?
- Apo B-100
- Apo E
Where is the largest amount of LDL receptors found?
In the liver
How is FH related to SREBP?
- Mutations in the sterol-sensing region of SCAP blocks sterol regulation in SREBP processing
- Activates SRE responsive genes (HMGCR, LDLR) if it senses low cholesterol (as it is in FH)
How does LXR increase fatty acid synthesis?
By inducing SREBP-1c
Which SREBP is implicated in glucose metabolism?
SREBP-1c
How does vitamin A regulate the expression of specific target genes?
Through its binding to nuclear RARs and RXRs
Where is Apo E synthesized?
In the liver
What does HDL exchange with chylomicrons in circulation?
- HDL exchanges Apo E and Apo C
- CM exchange Apo A-I and Apo A-IV
What does CETP convert?
HDL2 to HDL3
What is the consequence of CETP deficiency?
Causes high plasma levels of HDL
What is the consequence of Tangier disease? What is it caused by?
- Nearly total absence of HDL
- Molecular lesion in ABCA1 gene
Which genetic disorders cause elevated LDL?
- FH
- PCSK9
- Familial defective Apo B
- Autosomal recessive hypercholesterolemia
Which genetic disorders cause elevated HDL?
- CETP deficiency
- Hepatic lipase deficiency
Which genetic disorders cause low HDL?
- Tangier disease
- LCAT deficiency
- Apolipoprotein A-1 deficiency
Which genetic disorders cause low TG or cholesterol?
Abetalipoproteinemia
What is FH treated with?
Combination of statin and ezetimibe
Which apolipoproteins are not present in abetalipoproteinemia? Which ones are?
- No Apo-B particles are present
- Only HDLs
