Lecture 26: Lipids and Lipoproteins

Question 1

What are some sources of Acetyl CoA?

Answer 1

Pyruvate
Fatty Acids
Amino Acids

Question 2

How many units of IPP form a sterane ring?

Answer 2

6 units

Question 3

Describe the structure of cholesterol.

Answer 3

Sterane Ring
Hydrocarbon Ring
Hydroxyl group
27 carbons total

Question 4

Where is cholesterol utilized?

Answer 4

Bile acids and salts
Vitamin D
Steroid Hormones

Question 5

What enzyme breaks down cholesterol?

Answer 5

None! Instead it is excreted or used biochemically

Question 6

How does Acetyl CoA become IPP?

Answer 6

Acetyl CoA –> Acetoacetyl CoA –> HMG CoA –> Mevalonate –> IPP

Question 7

What is the rate limiting step when Acetyl CoA become IPP?

Answer 7

HMG CoA Reductase

HMG CoA –> Mevalonate

Question 8

What can inhibit HMG CoA Reductase?

Answer 8

Statins

Question 9

What can be the fate for IPP?

Answer 9

Steroids
Lipid Soluble Vitamins
Other: Ubiquinone, Lipid Anchors

Question 10

How does IPP become cholesterol?

Answer 10

IPP –> Squalene –> Lanosterol –> Cholesterol

Question 11

What can inhibit lanosterol from becoming cholesterol?

Answer 11

Anti-fungal treatments

Tamoxifen

Question 12

How do statin drugs work?

Answer 12

Competitive inhibitors of HMG CoA reductase

Transcription of LDL receptor and subsequent clearance of cholesterol via endocytosis

Question 13

HMG CoA reductase is active in what form?

What can activate it?

Answer 13

Dephosphorylated form

Activated by insulin

Question 14

What are the important proteins that play a role in controlling in the HMG CoA reductase gene?

Answer 14

SREBP
SCAP
INSIG

Question 15

How does transcriptional control of HMG CoA reductase gene work?

Answer 15

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.

Question 16

What are the five different types of lipoproteins?

Answer 16

Chylomicrons
Very low density lipoproteins (VLDL)
Intermediate Density Lipoproteins (IDL)
Low Density Lipoproteins (LDL)
High Density Lipoproteins (HDL)

Question 17

What are some features of a chylomicron?

Answer 17

• Exogenous: formed from diet and made in intestines
• Largest
• Least Dense
• High concentration of TAGs

Question 18

What are some apolipoproteins found on a chylomicron?

What do they do?

Answer 18

ApoB-48: facilitates transport
ApoE: facilitates uptake into liver
ApoC-II: can break down triglycerides

Question 19

What are some apolipoproteins found on a VLDL?

What do they do?

Answer 19

ApoB-100: uptake into cells w/ corresponding receptor on cell
ApoE: facilitates uptake into liver
ApoC-II: can break down triglycerides

Question 20

What are some apolipoproteins found on a IDL?

What do they do?

Answer 20

ApoB-100: uptake into cells w/ corresponding receptor on cell
ApoE: facilitates uptake into liver

Question 21

What are some apolipoproteins found on a LDL?

What do they do?

Answer 21

ApoB-100: uptake into cells w/ corresponding receptor on cell

Question 22

Why is LDL considered “bad” cholesterol?

Answer 22

If it is not taken up by cells, can build up in arteries and cause atherosclerosis

Question 23

What are some features of HDL?

Answer 23

Smallest
Most dense
Mostly composed of proteins and phospholipids

Question 24

What are some apolipoproteins found on a HDL?

What do they do?

Answer 24

ApoA-I: esterifies cholesterol
ApoE: facilitates uptake into liver
ApoC-II: can break down triglycerides

Question 25

How are chylomicrons processed?

Answer 25

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

Question 26

How are VLDL, IDL, and LDL processed?

Answer 26

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

Question 27

What is the role of LDL?

Answer 27

Transport cholesterol to peripheral tissue | Regulate de novo synthesis

Question 28

What does a LDL particle contain?

Answer 28

Shell: phospholipids and free cholesterol | Packed w/ 1500 cholesterol ester molecules

Question 29

How is HDL processed?

Answer 29

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

Question 30

What are benefits of HDL?

Answer 30

- Helps mature chylomicrons via apolipoproteins | - Retrieves cholesterol from other tissues

Question 31

What is Tangier disease?

Answer 31

Rare lipoprotein disorder: almost complete absence of plasma HDL -loss of ABCA1

Question 32

What is Type I hyperlipoproteinemia?

Answer 32

- inability to hydrolyze TAGs in chylomicrons and VLDL - due to deficiency in Apo C-II or LPL - high levels of plasma TAGs - Autosomal recessive

Question 33

What are symptoms of Type 1 hyperlipoproteinemia?

Answer 33

Abdominal pain Acute pancreatitis Xanthomas

Question 34

What is Type II hyperlipoproteinemia?

Answer 34

Familial Hypercholesterolemia - mutations in LDL receptor - can cause atherosclerosis - high levels of LDL in blood - mild in heterozygous, serious in homozygous

Question 35

What can happen with atherosclerosis?

Answer 35

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