Yıldırım Beyazıt University Medical Faculty Biochemistry Department. Lipoproteins. Prof. Dr. Fatma Meriç YILMAZ [email protected] Lipids in the Blood. Fatty Acids Bound to albumin. Cholesterol, Triglycerides and Phospholipids Transported by lipoproteins
(Contain highest percentage of lipids and lowest percentage of proteins)
Provide recognition sites for cell-surface receptors
Serve as activators or coenzymes for enzymes involved in lipoprotein metabolism
Some of lipoproteins are essential structural components and cannot be removed
Some of them are transferred freely between lipoproteins
Apolipoproteins are divided into five groups by structure and function (A to E)
Most classes have subclasses like Apo A-I, Apo C-II etc.
Functions of all apolipoproteins are not yet known
HDL structural protein; LCAT activator;RCT
Hepatic Lipase activation
Tg metabolism; LCAT activator; dietresponse
Structural protein of all LP except HDL
Binding to LDL receptor
Inhibit Lp binding to LDL R; LCAT activator
LpL inhibitor; antagonizes apoE
B/E receptor ligandApolipoproteins
triacylglycerols and apolipoproteins
Chylomicrons are synthesized in intestinal epithelial cells, secreted into the lymph, pass into the blood, andbecome mature chylomicrons
On capillary walls in adipose tissue and muscle, lipoprotein lipase (LPL) activated by ApoCIIdigests the triacylglycerols (TG) of chylomicrons to fatty acids and glycerol.
Fatty acids (FA) are oxidized in muscle or stored in adipose cellsas triacylglycerols.
The remnants of the chylomicrons are taken up by the liver by receptor-mediated endocytosis (Apo E receptors). Lysosomal enzymes within thehepatocyte digest the remnants, releasing the amino acids, free cholesterol and fatty acidsinto the cytosol.
Apo-B48 is uniquetochylomicrons
Theparticlereleasedfromintestinalcellsarenamed as nascent CM andcarriesonlyApo B48
When it reachestotheplasma is has beenmodified; Apo C II andApo E particlesaretransferredfromHDL
Apo C II activates LPL enzyme
As thechylomicroncirculates, morethan 90% of TG in itscore is degradedby LPL, theparticledecreases in size, increases in density
C apoproteinsreturnto HDL andtheparticle is called a remnant CM
Remnant CM stillcontainsApo E andbindstotheliverthroughApo E receptors
CM Remnants are taken to the liver and hydrolized
Apo E receptor
VLDLs are produced in the liver
They are composed of predominantly of endogeneous triacylglycerol (60%)
The main function of VLDL is to carry this lipid from the liver to the peripheral tissues
The TG of VLDL, produced in the liver, isdigested by lipoprotein lipase (LPL) present on the lining cells of the capillaries in adiposeand skeletal muscle tissue. Fatty acids are released and either oxidized or stored in tissues asTG.
VLDL is secreteddirectlyintothebloodbytheliver as nascent VLDL particlescontainingApo B-100
TheymustobtainApo C-II andApo Efromcirculating HDL
Apo C-II activates LPL and as VLDL passthroughthecirculation, TGsaredegradedbylipoproteinlipase, causing VLDL todecrease in size andbecomedenser
Surfacecomponents, includingthe C and E apoproteinsarereturnedto HDL but theparticlesretainApo B-100
Finallysome TG aretransferredto HDL andcholesterolestersaretransferredfrom HDL to VLDL withCholesterol Ester Transfer Protein (CETP)
Withthesemodifications, VLDL is convertedto LDL in theplasma
Intermediate-density lipoproteins are formed from the degradation of VLDLs
Some of the IDL particles are rapidly taken up by the liver through Apo E receptors; others remain in circulation, where they undergo further triglyceride hydrolysis and are converted to LDL
Carry Apo E and Apo B-100
LDL particles contain much less TG then their precursor VLDL and have a high concentration of cholesterol and cholesteryl esters
The primary function of LDL is to provide cholesterol to peripheral tissues
LDL particles contain Apo B100
which is the receptor binding site for LDL particles
These receptors can also bind Apo E and are named as Apo B100/Apo E receptors
LDL is taken up with
Apo B100 receptors
HDL comprise a heterogeneous family of lipoproteins with a complex metabolism that is not completely understood.
HDL is a reservoir of apolipoproteins Apo C-II and Apo E
HDL takes up the cholesterol esters from peripheral tissues and returns it to the liver
It is responsible from esterification of cholesterol with LCAT enzyme
Nascent HDL are disk shaped particles containing primarily phospholipid and Apo A, C and E
They take up cholesterol from peripheral tissues and return it to liver as CE.
When chol is taken up by HDL, it is immediately esterified with LCAT
LCAT enzyme is synthesized by the liver.
LCAT binds to nascent HDL and is activated by Apo A-I
LCAT transfersthefattyacidfromcarbon 2 of phosphotidylcholintocholesterol
Thisproduces a hydrophobiccholesteryl ester which is transferredtothecore of thelipoprotein
As thediscoidalnascent HDL accumulatescholesterylesters, it firstbecomes a spherical, relativelycholesteryl ester poorHDL3 thenturnstoHDL2 which is cholesteryl ester rich HDL form.
HDL receptor mediated
endocytosis in liver
Transfer of some CE
To VLDL (CETP)
“used” cholesterol is
Transferred to HDL and converted
to cholesteryl esters (LCAT)
Cholesterol is secreted to bile or
repackaged to form VLDL
American Heart Association, 2000.
It is also known as hyperlipidemia or hyperlipoproteinemia
It is defined as a presence of raised or abnormal levels of lipids and/or lipoproteins in the blood
This abnormality is common in the general population, and is one of the important modifiable risk factors for coronary heart disease (CHD).
Dyslipidemia is generally characterized by increased fasting concentrations of total cholesterol (TC), LDL cholesterol (LDL-C), and triglycerides (TG), in conjunction with decreased concentrations of HDL cholesterol (HDL-C)
Apo E receptor
Usually high lipid levels are asymptomatic
Occasionally when fat levels are high, it can be deposited in skin and tendons forming bumps called xanthomas (eyes and Achilles tendon)
Very high triglyceride levels may cause liver to enlarge
High lipids increase the risk of developing pancreatitis, which causes severe abdominal pain and is sometimes fatal
(Freidewald=TK-HDL-VLDL or direct LDL)
VLDL Cholesterol (TG/5)