Lecture 26: Lipids and Lipoproteins Flashcards
What are some sources of Acetyl CoA?
Pyruvate
Fatty Acids
Amino Acids
How many units of IPP form a sterane ring?
6 units
Describe the structure of cholesterol
Sterane Ring
Hydrocarbon Ring
Hydroxyl group
27 carbons total
How is cholesterol utilized?
Bile acids and salts
Vitamin D
Steroid Hormones
What enzyme breaks down cholesterol?
None! Instead it is excreted or used biochemically
How does Acetyl CoA become IPP?
Acetyl CoA –> Acetoacetyl CoA –> HMG CoA –> Mevalonate –> IPP
What is the rate limiting step when Acetyl CoA become IPP?
HMG CoA Reductase
HMG CoA –> Mevalonate
What can inhibit HMG CoA Reductase?
Statins
What can be the fate for IPP?
Steroids
Lipid Soluble Vitamins
Other: Ubiquinone, Lipid Anchors
How does IPP become cholesterol?
IPP –> Squalene –> Lanosterol –> Cholesterol
What can inhibit lanosterol from becoming cholesterol?
Anti-fungal treatments
Tamoxifen
How do statin drugs work?
Transcription of LDL receptor and clearance of cholesterol via endocytosis
HMG CoA reductase is active in what form?
What can activate it?
Dephosphorylated form
Activated by insulin
What are the important proteins that play a role in controlling in the HMG CoA reductase gene?
SREBP
SCAP
INSIG
How does transcriptional control of HMG CoA reductase gene work?
When cholesterol is high, SREBP is the ER membrane and bound to SCAP and INSIG.
When cholesterol is low, SREBP-SCAP complex translocates to Golgi apparatus. SREBP is cleaved and binds to a sterol regulatory element to promote cholesterol production and enhance uptake into cells.
What are the five different types of lipoproteins?
Chylomicrons Very low density lipoproteins (VLDL) Intermediate Density Lipoproteins (IDL) Low Density Lipoproteins (LDL) High Density Lipoproteins (HDL)
What are some features of a chylomicron?
- Exogenous: formed from diet and made in intestines
- Largest
- Least Dense
- High concentration of TAGs
What are some apolipoproteins found on a chylomicron?
What do they do?
ApoB-48: facilitates transport
ApoE: facilitates uptake into liver
ApoC-II: can break down triglycerides
What are some apolipoproteins found on a VLDL?
What do they do?
ApoB-100: uptake into cells w/ corresponding receptor on cell
ApoE: facilitates uptake into liver
ApoC-II: can break down triglycerides
What are some apolipoproteins found on a IDL?
What do they do?
ApoB-100: uptake into cells w/ corresponding receptor on cell
ApoE: facilitates uptake into liver
What are some apolipoproteins found on a LDL?
What do they do?
ApoB-100: uptake into cells w/ corresponding receptor on cell
Why is LDL considered “bad” cholesterol?
If it is not taken up by cells, can build up in arteries and cause atherosclerosis
What are some features of HDL?
Smallest
Most dense
Mostly composed of proteins and phospholipids
What are some apolipoproteins found on a HDL?
What do they do?
ApoA-I: esterifies cholesterol
ApoE: facilitates uptake into liver
ApoC-II: can break down triglycerides
How are chylomicrons processed?
1) Nascent Chylomicrons: assembled in small intestine and transported through lymphatic system to blood stream
- only has ApoB-48
2) Mature Chylomicrons: additional apolipoproteins are added
3) ApoC-II: TAGs are hydrolyzed
4) Remnants of chylomicrons are endocytosed by liver via ApoE
How are VLDL, IDL, and LDL processed?
1) VLDL produced in liver and released into bloodstream.
2) ApoC-II: TAGs are hydrolyzed –> IDL
3) Cholesterol in IDL is delivered to liver and continues to lose more TAGs
4) LDL deliver cholesterol to cells
What is the role of LDL?
Transport cholesterol to peripheral tissue
Regulate de novo synthesis
What does a LDL particle contain?
Shell: phospholipids and free cholesterol
Packed w/ 1500 cholesterol ester molecules
How is HDL processed?
1) Synthesized in liver and small intestine
2) Picks up cholesterol from peripheral tissues
3) Esterifies cholesterol and is in core
4) Donates ApoC-II and ApoE to chylomicrons
What are benefits of HDL?
- Helps mature chylomicrons via apolipoproteins
- Retrieves cholesterol from other tissues
Tangier disease:
Cause
Clinical
- HDL deficiency due to ABCA1 mutation. ABCA1 binds to ApoA1 on the HDL so cholesterol can be collected and brought to the liver or tissues for degradation/use
- premature atherosclerosis
What is Type I hyperlipoproteinemia?
What is the difference between the two types?
-defect in Apo-CII or lipoprotein lipases, so TAGs cannot be degraded, TAGs >1000 mg/dL (fatty blood sample)
Loss of LPL function - manifests in infancy
ApoC-II defect - post adolesence
What are symptoms of Type 1 hyperlipoproteinemia?
How do you treat this?
Abdominal pain
Acute pancreatitis
Xanthomas
-low fat diet
What is Type II hyperlipoproteinemia?
What are the symptoms?
How would you treat these?
aka Familial hypercholesterolemia. Caused by LDL receptor mutations leading to high LDL and atherosclerosis (homozygous worse than heterozygous - >800 mg/dL)
-xanthomas, angina, early CAD for homozygous patients
statin or diet changes for heterozygotes. LDL apheresis or transplantation for homozygotes
What can happen with atherosclerosis?
Accumulation of LDL can become oxidized in vessel wall
- increased vascular permeability and leukocyte adhesion
- initiates inflammatory responses
- macrophages become foam cells and forms plaques
- arteries can narrow and lead to heart attacks
