Lipoprotein Lecture (Lecture 4)

Question 1

Where is the VLDL created?

Answer 1

In the liver

Question 2

What does VLDL contain?

Answer 2

“Endogenous” TAGs and CEs (best thought of as a mixture of dietary and de novo synthesizes TAGs, with de novo TAGs predominanting)

Question 3

Percentage of lipids and protein in VLDL?

Answer 3

90% lipid, 10% protein

Question 4

How does the liver form triglycerides?

Answer 4

Liver synthesizes a small amount of fatty acids from excess dietary carbohydrate and esterifies these fatty acids into triglycerides. The liver esterifies some of these fatty acids into triglycerides into VLDL, which it releases into the blood

Question 5

Apolipoprotein on nascent VLDL?

Answer 5

Nascent VLDL enters the circulation containing Apo B-100 and amounts of Apo E and Apo C-II

Question 6

Where did nascent VLDL get Apo E and C-II?

Answer 6

Donated to VLDL from HDL

Question 7

Apolipoprotein on IDL?

Answer 7

Apo E and Apo B-100 (only difference between IDL and VLDL in terms of apolipoprotein is that VLDL has Apo C-II)

Question 8

Role of Apo C-II in forming IDL?

Answer 8

The presence of Apo C-II stimulates LPL to degrade the TAGS present in the particle, again resulting in the delivery of (liver-originating) fatty acids to adipose and other peripheral organs. The result of this action of LPL on the VDLD is its conversion to IDL (which is called the VLDL remnant)

Question 9

What is IDL?

Answer 9

VLDL remnant after LPL (lipoprotein lipase) activity - loss of Apo C-II

Question 10

What are the fates of the VLDL remnants?

Answer 10

Approximately half of the VLDL remnants are cleared from the circulation by the liver, via Apo E and its receptor. The remaining half are remodeled to LDL and remain in circulation.

Question 11

Remodeling IDL to LDL requires what?

Answer 11

The action of another lipase, hepatic lipase (HL), and the further elimination of both TAGs and PLs from the nascent LDL.

Question 12

Half-life of LDL?

Answer 12

on the order of days

Question 13

Half-life of VLDL?

Answer 13

expressed in terms of hours

Question 14

Half-lfe of chylomicrons?

Answer 14

expressed in terms of fractions of hours

Question 15

What lipoproteins constitute the majority of lipids observed in a fasting blood sample?

Answer 15

LDL, VLDL, and IDL

Question 16

Which lipoprotein contains the majority of blood-borne cholesterol?

Answer 16

LDL

Question 17

What is the apolipoprotein on LDL?

Answer 17

Apo B-100

Question 18

What is LDL synthesized from?

Answer 18

IDL

Question 19

Fate of LDL?

Answer 19

(1) liver
(2) peripheral tissue
- depending on their need for cholesterol, hepatocytes and peripheral cells display LDL-receptors on their surface, which they use to bind and endocytose LDL via their apo B-100

Question 20

LDL in the liver

Answer 20

Approximately two-thirds of circulating LDL is taken up by the livr via Apo B-100 binding to the LDL receptor

Question 21

LDL in peripheral tissue

Answer 21

Remaining third is taken up, for the most part via Apo B-100 and the LDL receptor, in peripheral tissues, thereby amounting to a significant source of cholesterol for these peripheral tissues (along with the endogenous synthesis)

Question 22

What dictates the expression of LDL receptors on cells?

Answer 22

Cells express LDL-receptors based on the concentration of cholesterol that the SREBP2 senses in the endoplasmic reticulum membrane. (remember when concentrations of cholesterol in the ER are abnormally, the n-terminal segment of REBP moves into the nucleus and enhances transcription of several genes - HMG-CoA reductase and LDL receptors)

Question 23

What is PCSK9?

Answer 23

PCSK9 secreted by the liver into the blood that prevents recycling of LDL-receptors. Instead, LDL-receptors are degrated by lysosomes after endocytosis of LDL.
** Important because this is a way to reduce LDL receptors on the plasma membrane **

Question 24

Are LDL receptors the only mechanism for clearing LDL particles?

Answer 24

No. Clearance, via the Scavenger receptor (SR-A)

Question 25

How does the Scavengar Receptor (SR-A) lead to clearance of LDL?

Answer 25

Macrophages possess SR-A. SR-A has a high affinity to oxidized (damaged) LDL. Sr-A leads to foam cell formation.
(The endocytosed particles are transported to the lysosomes, and free cholesterol (FC) is then released into the cytosol)

Question 26

mRNa editing of Apo B100

Answer 26

Apo B100 is made in the liver and small intestine. however, in the intestine only, the C residue in the codon (CAA) for glutamine is deaminated to U, changing the sense codon to a nonsense or stop codon (UAA). This results in a shorter protein (apo B-­48, representing
48% of the message) being made in the intestine (and incorporated into chylomicrons) than is made in the liver (apo B-100, full­‐length, incorporated into VLDL).