Flashcards in Lipoprotein Lecture (Lecture 4) Deck (26):
Where is the VLDL created?
In the liver
What does VLDL contain?
"Endogenous" TAGs and CEs (best thought of as a mixture of dietary and de novo synthesizes TAGs, with de novo TAGs predominanting)
Percentage of lipids and protein in VLDL?
90% lipid, 10% protein
How does the liver form triglycerides?
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
Apolipoprotein on nascent VLDL?
Nascent VLDL enters the circulation containing Apo B-100 and amounts of Apo E and Apo C-II
Where did nascent VLDL get Apo E and C-II?
Donated to VLDL from HDL
Apolipoprotein on IDL?
Apo E and Apo B-100 (only difference between IDL and VLDL in terms of apolipoprotein is that VLDL has Apo C-II)
Role of Apo C-II in forming IDL?
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)
What is IDL?
VLDL remnant after LPL (lipoprotein lipase) activity - loss of Apo C-II
What are the fates of the VLDL remnants?
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.
Remodeling IDL to LDL requires what?
The action of another lipase, hepatic lipase (HL), and the further elimination of both TAGs and PLs from the nascent LDL.
Half-life of LDL?
on the order of days
Half-life of VLDL?
expressed in terms of hours
Half-lfe of chylomicrons?
expressed in terms of fractions of hours
What lipoproteins constitute the majority of lipids observed in a fasting blood sample?
LDL, VLDL, and IDL
Which lipoprotein contains the majority of blood-borne cholesterol?
What is the apolipoprotein on LDL?
What is LDL synthesized from?
Fate of LDL?
(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
LDL in the liver
Approximately two-thirds of circulating LDL is taken up by the livr via Apo B-100 binding to the LDL receptor
LDL in peripheral tissue
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)
What dictates the expression of LDL receptors on cells?
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)
What is PCSK9?
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 **
Are LDL receptors the only mechanism for clearing LDL particles?
No. Clearance, via the Scavenger receptor (SR-A)
How does the Scavengar Receptor (SR-A) lead to clearance of LDL?
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)