aa summary of lipoproteins, how dietary lipids are carried in the circulation, in what form, and how they would be rather stored or utilized.

1. Lipoproteins
Lipoproteins-1
 LP are hydrophobic (cholesterol, TAGs and CE) in core, and hydrophilic from
outside (phospholipids & proteins).
 Cholesterol –OH group is located on the outside.
 In CE, the –OH is esterified to a Fatty acid.
 There will be a question about density and mobility (charge) of LP.
In elcectrophoretic mobility test, chylomicrons don’t move they stay at the
origin, so they have the least mobility.
 Regarding mobility (chylomicrons<LDL<VLDL<HDL)
 Regarding density (chylomicrons<VLDL<IDL<LDL<HDL)
 You have to know these

2. ------------------------------------------------------------------------------------------------------------
 Chylomicrons are synthesized from the exogenous lipoprotein pathway.
 What are the major apolipoproteins of the chylomicrons
1-apo B48
2-apo CII
3-apo E
 What does apo-CII do? ............................................. ans. It activates LPL
 Once LPL is activated,
1- It hydrolyzes chylomicrons.
2- Releases free fatty acids from core TAGs to be
–stored in adipose tissue and mammary cells or
-oxidized in muscle cells
 After the chylomicrons are hydrolyzed by LPL, apoCII is now lost.
-apoCII is not really lost. It will be given back to the HDL.
 Then the chylomicrons are now called chylomicron remnants
 They lost apoCII
 They lost most of their core TAGs
 Rich in CE

3.  Chylomicron remnants are taken up by the liver by receptor-mediated
endocystosis. (Through the binding of apoE to its receptor on liver cells),
where they will be degraded by lysosomes.
 Important to note that;
 ApoB48 is added to the chylomicrons in the intestinal mucosa
(nascent chylomicron)
 ApoCII and apoE are transferred from HDL to LDL.
(mature chylomicron) (Fig.25.3)
--------------------------------------------------------------------------------------------------------
 You should know why VLDL is formed... (Due to excess carbs in body which
are converted to TAGs endogenously that along with cholesterol and CE and
apoB100 will form nascent VLDL.
 Nascent VLDL-->endogenously synthesized TAGs +cholesterol & CE +apoB100
 Mature VLDL-->endogenous TAGs +cholesterol & CE +apoB100 +apoCII +apoE
 After activation of LPL by apoCII and release of most of the TAGs, VLDL is
now called IDL or VLDL remnants.
 IDL then transfers apoE back to the HDL
 IDL now will have mainly 2 fates.
 It can be endocytosed and degraded by the liver.
 Or further digested by hepatic TG lipase (HTGL) to form LDL
(Fig..18)
 What does HTGL do??................................
Ans. It degrades the TAGs remaining in the IDL converting it to LDL.
 LDL is rich in cholesterol and CE.
 60% goes back to liver (receptor-mediated endocytosis by apoB100)
 40% goes to extrahepatic tissues such as adrenal cortex and gonads
where LDL cholesterol is used synthesize steroid hormones. (Fig.34.18)
 High intracellular cholesterol concentration induces the storage of
cholesterol, and inhibits the expression of LDL receptors.

4.  Where can we find LDL receptors?? …………………
ans. Mainly on the membrane of liver cells, adrenal cortex cells, and gonadal
cells
 LDL receptors contain a unique clathrin protein, once the LDL-receptor
complex is endocytosed to the inside of the cell in a vesicle, this vesicle fuses
with lysosomes and its contents are freed up. CEs are hydrolyzed to free
cholesterol but once the degradation process ends, all the free cholesterol
molecules are re-esterified by ACAT to be trapped within the cell.
 Lipoprotein receptors can recognize both apoB100 and apoE.
 Any mutation in the LDL receptor gene can result in hypercholesterolemia.
 When LDL receptors in hepatic and extrahepatic tissues become saturated
due excess LDL particles, the excess LDL can oxidized and taken up scavenger
receptors on macrophages present near the endothelial cells of arteries.
1) And after taking certain amount of oxLDL, they will be called foam
cells.
2) Foam cells induce migration of SMCs from media layer to intima
layer. And SMCs will start uptaking oxLDL and become foam cells.
3) This will initiate the cascade of atherosclerosis.
Lipoproteins-2
 3 ways to synthesize HDL
 Synthesize a nascent HDL by liver and intestines similar in its main
structure to the other lipoproteins but it has specific apoproteins (AI,
AII, CI, CII) mainly.
 Budding of apoproteins from chylomicrons and VLDL particles as they
are digested by LPL.
 Free apoAI can acquire cholesterol and phospholipids from other LP
and from cell membranes forming a nascent HDL within the
circulation.
 Nascent HDL has a hollow core with very low levels of CE and TAGs, and
outer shell with free cholesterol and phospholipids.
Fig.18.22

5.  Once this core gets filled with CE and the outer shell acquires more
cholesterol and phospholipids (from cells lining the blood vessels), the
nascent HDL is now called mature HDL that now has a distinct globular
shape. (No enzymes used)..
 What is reverse cholesterol transport?..............
1. HDL picks up cholesterol from cell membranes.
2. This cholesterol is converted to CE in the HDL by the LCAT reaction.
3. HDL transfers CE to the liver by binding to specific receptor on
hepatocytes SR-B1 (mentioned later) through the apoAI.
 Cholesterol from cell membranes to HDL
1. Cells contain the protein ABC1 (ATP-binding cassette protein 1)
which uses ATP hydrolysis to move cholesterol from the inner
leaflet of the membrane to the outer leaflet.
2. Cholesterol particles then move out of the cell membrane and enter
the HDL.
3. Cholesterol as a hydrophobic molecule must be trapped in the HDL
so it will be converted to CE by the enzyme (lecithin-cholesterol
acyltransferase) LCAT (synthesized in liver), LCAT catalyzes the
transfer of a fatty acid from the 2-position of lecithin
(phosphatidylcholine) in the phospholipid shell of the HDL to the 3-
hydroxyl group of cholesterol, forming a cholesterol ester.
 HDL is considered as a vasculoprotective particle.
 Receptors of HDL on hepatocytes are apoE receptor and Scavenger
receptors (SR-B1).
 ApoE is found only on hepatocytes but SR-B1 is found in many cell types,
and since HDL is widely utilized by many cell types, SR-B1 is considered to
be the primary mean to uptake and clear HDL particles.
 We mentioned one fate of cholesterol and CE of the HDL by being
returned back to the liver.

6.  Another fate is that, HDL can transfer CE to VLDL and
chylomicrons in exchange for triacylglycerol (TG). The cholesterol ester
transfer protein (CETP) mediates this exchange.
₰ Mature HDL= HDL3
₰ After reverse cholesterol transport =HDL2 (atherogenic protective form)
₰ After exchanging CE for TAGs with VLDL and chylomicrons = HDL3
regenerated
₰ After hepatic lipase removing the TAGs from it= HDL2
………. Fig.2.2 (summary of HDL cycle)

8. Illustrations
(Fig.1.1)

9. ---------------------------------------------------------------------------------------------------

12. -THE END-

13. References
 Marks’ Basic Medical Biochemistry: A Clinical
Approach Fourth Edition
 Harper’s Illustrated Biochemistry, Twenty-Sixth
Edition
 Koolman, Color Atlas of Biochemistry, 2nd edition ©
2005 Thieme Usage subject to terms and conditions of
license. All right preserved.
 Lippincott’s Illustrated Reviews: Biochemistry 5th
Edition
 Lehninger principles of biochemistry 4th
Edition.
Done by// Aly Ahmed Barakat
4th
year MD student in OMC