Lipo protein metabolism

explains lipo protein action and their clinical importance

1. LIPO PROTEIN METABOLISMLIPO PROTEIN METABOLISM
Dr. V. Siva Prabodh Dr. V. Siva Prabodh MDMD
ProfessorProfessor
Dept. of BiochemistryDept. of Biochemistry
NRI Medical CollegeNRI Medical College

2. LipoproteinsLipoproteins
These are molecular complexes which contains These are molecular complexes which contains
Lipids & proteinsLipids & proteins
FunctionFunction: : Transports Lipids in blood.Transports Lipids in blood.
Classification of LipoproteinsClassification of Lipoproteins
Five Major classesFive Major classes
1)1)ChylomicronsChylomicrons
2)2)VLDLVLDL
3)3)LDLLDL
4)4)HDLHDL
5)5)FFA with albuminFFA with albumin

3. Lipo proteins are seperated by Lipo proteins are seperated by
Ultra Ultra
centrifugation/Electrophoresiscentrifugation/Electrophoresis

5. 1)1)ChylomicronsChylomicrons:: Synthesized in the Intestine. Synthesized in the Intestine.
Transport Exogenous lipids (Dietary Lipids)Transport Exogenous lipids (Dietary Lipids)
99% Lipids, 1% protein, Density very less.99% Lipids, 1% protein, Density very less.
2)2)VLDL :VLDL : Produced in the Liver & Intestine Produced in the Liver & Intestine
Transport Endogenous lipidsTransport Endogenous lipids

6. 3) 3) LDLLDL : : Formed from VLDL in blood Formed from VLDL in blood
Transport cholesterol from Liver to Transport cholesterol from Liver to
other tissues. other tissues.
4) 4) HDLHDL : : Mostly synthesized in Liver Mostly synthesized in Liver
Transport cholesterol from Transport cholesterol from
peripheral tissues to Liver (Reverse peripheral tissues to Liver (Reverse
cholesterol transport) cholesterol transport)
5) 5) FFA with albuminFFA with albumin: Each molecule : Each molecule
of albumin hold 20-30 molecules of of albumin hold 20-30 molecules of
FFA. FFA.

7. ApolipoproteinsApolipoproteins
•Structural determinants of
lipoproteins
•Enzyme cofactors
•Ligands for binding to
lipoprotein receptors

8. ApoproteinsApoproteins
The protein forms of Lipoproteins are known as The protein forms of Lipoproteins are known as
Apolipoproteins or Apoproteins.Apolipoproteins or Apoproteins.
Functions: Functions:
1)1)Structural component – Structural component – apo A, apo Bapo A, apo B
4848, apo B, apo B
100100
apo Capo C
2)2)Recognizes surface receptors – Recognizes surface receptors – apo E, apo Bapo E, apo B
100100
3)3)Activate Lipoprotein Lipase – Activate Lipoprotein Lipase – apo C IIapo C II

9. ChylomicronsChylomicrons

10. VLDLVLDL

11. LDLLDL
Low density Lipoprotein is formed from VLDL and the Low density Lipoprotein is formed from VLDL and the
Intermediate is IDL.Intermediate is IDL.
LDL contain high cholesterol and less TAGLDL contain high cholesterol and less TAG. .
FunctionFunction:– Supply cholesterol to extra hepatic tissues.:– Supply cholesterol to extra hepatic tissues.
LDL particles bind to specific receptors over the cell LDL particles bind to specific receptors over the cell
membrane which are membrane which are clathrin coated pitclathrin coated pit
Apo BApo B
100100 recognizes the receptors over the cell membrane recognizes the receptors over the cell membrane
Deficiency of LDL receptors leads to Increased circulating Deficiency of LDL receptors leads to Increased circulating
LDL and hence cholesterol increases LDL and hence cholesterol increases
Eg: Type IIa hyperbeta lipoproteinemia.Eg: Type IIa hyperbeta lipoproteinemia.

12. From Medical Biochemistry,
Baynes & Dominiczak,
Mosby, 1999.

13. Enzymes and Transfer ProteinsEnzymes and Transfer Proteins
• LCAT (Lecithin:Cholesterol Acyltransferase)
•Formation of cholesterol esters in lipoproteins
• ACAT (Acyl-CoA:Cholesterol Acyltransferase)
•Formation of cholesterol esters in cells
• CETP (Cholesterol Ester Transfer Protein)

14. HDL HDL
High density Lipoproteins (Three types HDLHigh density Lipoproteins (Three types HDL
11, HDL, HDL
2, 2, HDLHDL
33))
Cholesterol is transported from Extra hepatic tissue to Liver Cholesterol is transported from Extra hepatic tissue to Liver
where it is excreted in the form of bile.where it is excreted in the form of bile.
Anti – atherogenicAnti – atherogenic, , Good cholesterolGood cholesterol
Intestinal cells synthesize HDL and release into blood.Intestinal cells synthesize HDL and release into blood.
LCAT:LCAT: Lecithin cholesterol Acyl transferases, transfer Lecithin cholesterol Acyl transferases, transfer
PUFA from Lecithin to cholesterol to form cholesterol ester, PUFA from Lecithin to cholesterol to form cholesterol ester,
which moves into interior of HDLwhich moves into interior of HDL
APO A IAPO A I activates LCAT activates LCAT
The HDL with more cholesterol are taken up by Liver cells, The HDL with more cholesterol are taken up by Liver cells,
and cholesterol is released into Liver. (Reverse cholesterol and cholesterol is released into Liver. (Reverse cholesterol
transport)transport)

16. HYPER LIPOPROTEINEMIASHYPER LIPOPROTEINEMIAS

HLP-Phenotypes (Fredrickson, WHO)
Lipoproteins Lipids Defect
I Chylomicron TG LP lipase
IIA LDL LDL-C LDL-receptor
IIB LDL + VLDL LDL-C, TG HMG.CoA reductase
III IDL TC, TG Apo-E deficiency
IV VLDL TG VLDL overproduction
V Chylomicron + VLDL TG Apo-C2 deficiency

17. From Medical Biochemistry,
Baynes & Dominiczak,
Mosby, 1999.

18. Familial hypercholesterolemia
(type II a)
Recepto r-media ted up take of
LDL i s one of the best
understood exa mples of
recepto r-media ted
endocyto sis. LDL is a
pro tein-lipid complex tha t
transpo rts c holesterol-fatty
acid esters in the blood
strea m. LDL no rmally
supplies c holesterol to cells.
Defec ts in the endocy tic
process resul t in hig h blood
levels of LDL. High LDL
predispo ses individuals for
atherosclero sis.
1
Apo-
B100
Apo-E
Dominantly inherited
disorder
- deficiency in a cell surface
LDL-R (the receptor regulates
LDL degradation and
cholesterol synthesis)
high cholesterol (since birth)
high LDL-C leads to premature
atherosclerosis, xanthomas
of skin and tendons
Total Cholesterol>240mg/dl
LDL>190 mg/dl

19. XanthomasXanthomas
raised lesions related to raised lesions related to
hyperlipidemiahyperlipidemia
Eruptive Xanthomas
-generally associated with
hypertriglyceridemia
Xanthomas of the eyelid
-generally associated with
hypercholesterolemia

21. Case StudyCase Study
– familial hypercholesterolemia– familial hypercholesterolemia
8 yr girl8 yr girl
Admitted for heart/liver transplantAdmitted for heart/liver transplant
HistoryHistory
CHD in familyCHD in family
2 yr xanthomas appear on legs2 yr xanthomas appear on legs
4 yr xanthomas appear on elbows4 yr xanthomas appear on elbows
7 yr admitted w/ MI symptoms7 yr admitted w/ MI symptoms
[TC] = 1240 mg/dl[TC] = 1240 mg/dl
[TG] = 350 mg/dl[TG] = 350 mg/dl
[TC]father = 355 mg/dl[TC]father = 355 mg/dl
[TC]mother = 310 mg/dl[TC]mother = 310 mg/dl
2 wks after MI had coronary bypass surgery2 wks after MI had coronary bypass surgery
Despite low-fat diet, cholestyramine, & lovastatin, [TC] = 1000 Despite low-fat diet, cholestyramine, & lovastatin, [TC] = 1000
mg/dlmg/dl

22. ThankThank youyou