CHEMISTRY OF LIPOPROTEINS

1. Lipoproteins
Gandham.Rajeev
Email:gandhamrajeev33@gmail.com

2. Introduction
• Lipoproteins are molecular complexes that
consist of lipids & proteins (conjugated
proteins).
• Protein part is called apolipoprotein.
• Usually abbreviated as Lp.
• They function as transport vehicles for lipids in
blood plasma.
• Lipoproteins deliver the lipid components
(cholesterol, TAG etc.) to tissues for utilization.

3. Classification of lipoproteins
• Depending on the density by
ultracentrifugation or electophoretic mobility,
the lipoproteins are classified as 5 major types.
1. Chylomicrons-contains apoprotein B48.
2. Very low density lipoproteins (VLDL) or
prebeta lipoproteins.
• Main apoprotein is B-100.

4. 3. Intermediate density lipoproteins (IDL) or
broad-beta lipoproteins.
4. Low density lipoproteins (LDL) or
betalipoproteins.
• Major apoprotein in LDL is B-100.
5. High density lipoproteins (HDL) or
alphalipoproteins.
• Major apoprotein in HDL is apo-A.
• Free fatty acids (FFA) or nonesterified fatty
acids (NEFA) are complexed with albumin.

7. Chylomicrons
• Synthesized in the intestine & transport
exogenous (dietary) TAGs to various tissues.
• Contains apoprotein B-48.
• They consist of highest (99%) quantity of lipid &
lowest (1%) concentration of protein.
• The chylomicrons are the least in density &
largest in size.

8. Very low density lipoproteins (VLDL)
• Pre β-lipoproteins.
• Main apoprotein is B-100.
• They are produced in liver & intestine.
• Responsible for the transport of
endogenously synthesized triacylglycerols.

9. Low density lipoproteins (LDL)
• β-lipoprotein.
• They are formed from VLDL in the blood
circulation.
• They transport cholesterol from liver to other
tissues.

10. High density lipoproteins (HDL)
• α-lipoproteins.
• Major apoprotein in HDL is apo-A.
• They are mostly synthesized in liver.
• Three different fractions of HDL (1, 2 & 3)
identified by ultracentrifugation.
• HDL particles transport cholesterol from
peripheral tissues to liver (reverse cholesterol
transport).

11. Free fatty acids or non-esterified fatty acids
• Free fatty acids or non-esterified fatty acids
(NEFA) are complexed with albumin.
• Loosely bound to the protein-albumin.
• Each molecule of albumin can hold about 20-30
molecules of free fatty acids.

12. Structure of lipoproteins
• Lipoprotein consists of inner core (hydrophobic
triacylglycerol, cholesterylester & tails of
phospholipids) surrounded by a coat shell of
phospholipids, apoproteins & cholesterol.

13. • The polar head portions (hydrophilic) of
phospholipids & cholesterol are exposed on
the surface of lipoproteins.
• So that lipoprotein is soluble in aqueous
solution.
• The apoproteins also increase the solubility of
lipids.

14. Apo-lipoproteins
• Protein part of lipoprotein is called as
apolipoprotein (apo-Lp) or apoprotein.
• Synthesis:
• All apoproteins are synthesized in liver.
• Small quantities are produced from almost all
organs.
• Intestinal cells produce small quantities of
apo-A.
• They will solubilize the lipid part.

15. Functions of apolipoproteins
• Apo A-1:
• It activates LCAT.
• It is the ligand for HDL receptor.
• It is anti-atherogenic.
• It is specific for HDL.
• Apo B-100:
• Only apoprotein component of LDL.
• It binds to LDL receptors on tissues.

16. • It is one of the biggest proteins, having 4536
amino acids, & molecular weight is 550 kDa.
• Synthesized in liver.
• Apo B-48:
• Major apoprotein of chylomicrons.
• Synthesized only in intestinal cells.
• Apo-B-100 & apo-B-48 are products of same
gene.

17. • In intestine, mRNA undergoes editing, to
produce only B-48 protein.
• B-48 is named because it is only 40% of the size
of B-100.
• Apo-C-II:
• Activates lipoprotein lipase.
• Apo-E:
• Arginine rich protein.

18. • Present in chylomicrons, LDL & VLDL.
• Astrocytes also make apo-E.
• It is involved in transport of lipids in CNS.
• Apo-E has I,II,III & IV isoforms.
• Apo-E-IV is implecated in the development of
Alzheimer’s disease.
• Apo-E is also associated with glomerulopathy.

19. Chylomicrons
• Synthesis:
• Formed in intestinal mucosal cells, secreted
into the lymphatic system.
• Rich in triglycerides.
• When chylomicrons are synthesized by
intestinal mucosa, contain apo-B-48 & apo-A.
• Apo-C & apo-E are added from HDL in blood
during transport.

20. Structure of Chylomicrons

21. Metabolism of chylomicrons
• Site of metabolism:
• Adipose tissue & skeletal muscle.
• Half-life in blood is about 1 hour
• Lipoprotein lipase (LpL) is located at
endothelial layer of capillaries of adipose
tissue, muscles & heart.
• This enzyme is absent in liver.

22. • Apo-CII present in chylomicrons activates LpL.
• LpL hydrolyzes TGL present in chylomicrons
into fatty acids & glycerol.
• Muscles or adipose tissue cells takes up the
liberated fatty acids.
• Injection of heparin, LpL is released from
tissues & lipiemia is cleared.

23. • This is called as post-heparin lipolytic activity.
• Lack of C-II leads to decreased activity of LpL
& accumulation of chylomicrons & VLDL.
• Insulin increases LpL activity.
• Liver takes up chylomicron remnants:
• As TGL content is progressively decreased,
chylomicrons shink in size.

24. • These remnants containing apo-B-48 & apo-E
are taken up by hepatic cells by receptor
mediated endocytosis.
• Apo-E binds the hepatic receptors.

25. Chylomicrons Metabolism

26. Functions
• Transport of dietary TGL from intestine to
adipose tissue for storage.
• To muscle & heart for their energy needs.

27. Very low density lipoproteins
• Synthesis:
• Synthesized in the liver from glycerol & fatty
acids & incorporated into VLDL, along with
hepatic cholesterol, apo-B-100,C-II & E.
• Apo-B-100 is major lipoprotein in VLDL.
• Apo-E & C-II are obtained from HDL in plasma.

28. Metabolism of VLDL
• Half-life of VLDL is 1 to 3 hrs.
• In peripheral tissues, apo C-II activates LpL
which liberates fatty acids that are taken up
by adipose tissue & muscle.
• The remnant is called as IDL.
• IDL contains less of TAG & more of cholesterol.
• IDL further loses TAG, & converted to LDL.

29. • This conversion of VLDL to IDL & then to LDL is
referred to as lipoprotein cascade pathway
• IDL is taken up by hepatic receptors.
• Functions of VLDL.
• VLDL carries triglycerides (endogenous
triglycerides) from liver to peripheral tissues
for energy needs.

30. References
• Textbook of Biochemistry-U Satyanarayana
• Textbook of Biochemistry-DM Vasudevan

31. Thank You