three-hypers series - hyperlipidemia - 03 what are lipoproteins?

(lipoprotein)

(enzymes)(transporters)(structural proteins)(antigens)(adhesins)(toxins)

Manyenzymes,transporters, structural proteins,antigens,adhesins, andtoxinsare lipoproteins.

Examples include theplasma lipoprotein particlesclassified underhigh-density(HDL) andlow-density(LDL) lipoproteins, which enable fats to be carried in thebloodstream, thetransmembrane proteinsof themitochondrionand thechloroplast, and bacterial lipoproteins.

(mitochondrion)(chloroplast)(transmembrane proteins)

(bacterial lipoproteins)

()(A, K, DE)

A core of fats (triglycerides), cholesterol esters (cholesterol linked to fatty acids), and fat-soluble vitamins.A monolayer membrane of phospholipids and small amounts of free cholesterol.Proteins called apoprotein which may be integral apoproteins (apoA or apoB) penetrating as a transmembrane protein through the monolayermembrane, compared to the peripheral apoproteins (apoCor apoE) that are on the outer surface of the phospholipid membrane.

(Apoprotein/Apolipoprotein)

(Apoprotein/Apolipoprotein)1. marker2. 3.

(lipoprotein)

2(Apo AApo B)


2(Apo CApo E)


()()()

The lipid components of lipoproteins are insoluble in water. However, because of their detergent-like (amphipathic) properties, apolipoproteins and other amphipathic molecules (such asphospholipids) can surround the lipids, creating the lipoprotein particle that is itself water-soluble, and can thus be carried through water-based circulation (i.e.,blood,lymph).

AA-IA-IIA-IVA-VBB 48B100

CC-IC-IIC-IIIC-IVDEH

5 18apoAapoB10048apoCapoDapoEapoJaCETPPTP

Apo A-IHDLchylomicrons1.2.LCAT(lecithin cholesterol acyltransferase)3.HDL(ligand)Apo B-100LDLVLDLIDL()1.VLDL2.LDLApo B-48ChylomicronsChylomicronApo C-IVLDLHDLchylomicronsLCATApo C-IIlipoprotein lipaseApo C-IIIApo C-IIApo E1.2.LDL

Apo B(cofactors)Apo C-II(lipoprotein lipase)Apo A-I(lecithincholesterol acyltransferaseLCAT)(inhibitors)Apo A-II Apo C-III(lipoprotein lipase)Apo C-I(cholesteryl esters transferase)(receptor)(ligand)Apo B-100Apo ELDL receptorApo A-IHDL receptor(Lipid transfer proteins)Apo DHDL

A(Apo-A)80% AA

B(Apo-B)BB

Apo-B Apo-A1 Apo-B / Apo-A1 CAD Apo-B Apo-A1 (Apo-B / Apo-A1 ratio ) CAD ( cholesterol, TG, HDL .. ) CAD

Apo-A1 Apo-B (Apo-B / Apo-A1 ratio )(CAD Coronary atherosclerosis disease ) Apo B/ Apo-A1 ratio < 0.5

(Biological membrane)

2.1(CM)0.952(VLDL)3(IDL)VLDLLDL4(LDL)5(HDL)HDL2HDL3

SvedbergSf1.0632610-13cm1Sf1Sf=10-13cm/s-dyn-g

(ChylomicronCM)

Chylomicron [.kailu'maikrn]

Chylomicronsare the lipoprotein packages transporting fat from our diet to adipose tissue in our body and the liver.


Our intestines package cholesterol, fats, and fat-soluble nutrients and vitamins into chylomicronsin the enterocytecell lining the small intestine. The apoproteinthat these lipoproteins get is apoB-48.Apo B-48

Apo B-48


Our intestines package cholesterol, fats, and fat-soluble nutrients and vitamins into chylomicronsin the enterocytecell lining the small intestine. The apoproteinthat these lipoproteins get is apoB-48.Apo B-48

(Chylomicron)

(Endoplasmic reticulum)(Golgi apparatus)(95)(5)

1.2.3.4.5.6.7.8.9.10.11.12.13.

Chylomicrons enter the lymphatic circulation and make their way via the thoracic lymph duct to the circulation where the duct empties into the subclavian vein in the neck.

The chylomicronstravel either to the liver or adipose tissue.

Apo B-48Apo C-IIApo E

In the blood stream the chylomicronsacquire two new apoproteins, both peripheral apoproteins; apoCand apoE. ;EE

Apo C-II CM

The chylomicronwill also bind preferentially to adipocytes via the apoClipoprotein to lipoprotein lipase(LPL) an enzyme on the surface of the adipocyte. C(lipoprotein lipase, LPL)

The LPLcleaves the triglycerides in the chylomicronand the glycerol and free fatty acids enter the adipocyte thus depleting the chylomicronof triglyceride content and filling the fat cell with fatty acids. LPL

(lipoprotein lipase,LPL)

()(remnant)

20Apo CApo B 48Apo E (chylomicron remnant)

When triglyceride is reduced to ~ 20% in the chylomicronthe apoCdissociates from the chylomicronand this reduced triglyceride lipoprotein with only apoB48and apoE is now called a chylomicron remnant.20CB 48E (chylomicron remnant)

(Apo E)

The chylomicronremnant is cleared from the circulation by the liver cell (hepatocytes) via the chylomicronremnant receptor on the hepatocytes, binding to the apoE on the remnant particle. The liver then makes use of the remaining triglyceride.ApoE(chylomicronremnant receptor)

CM5~15

(Very-low-density lipoprotein, VLDL)

VLDL

30~80 nm

VLDL


(Nascent)VLDLApo B 100Apo C1Apo E

VLDL carries mainly triglyceride and cholesterol ester (see table above) and the each VLDL containing one apoB100integral apoproteinin the monolayer membrane.

HDLApo CIIApo E

(Nascent)VLDL(Mature)VLDL

Nascent ,,

VLDL Apo CII(lipoprotein lipase, LPL)VLDL

lipoprteinlipaseLPL

Again identical to chylomicronsthe VLDL binds the adipocyte via the apoCto LPL on the adipocyte with the enzyme cleaving the triglyceride to glycerol and fatty acids to be used by the adipocyte.VLDLCLPL

Once in circulation, VLDL will come in contact withlipoprotein lipase(LPL) in the capillary beds in the body (adipose, cardiac, and skeletal muscle).

LPLVLDL

LPL will remove triglycerides from VLDL for storage or energy production.

VLDLHDLApo CIIHDL

VLDL now meets back up with HDL where apoC-II is transferred back to HDL (but keeps apoE). HDL also transfers cholesteryl esters to the VLDL in exchange for phospholipids and triglycerides viacholesterylester transfer protein(CETP).

HDL(cholesterylester transfer protein, CETP)VLDL


VLDL50VLDLLPL


Apo E(LDL-receptor, LDL-R)

As the triglyceride in the VLDL drops to 50% the VLDL dissociates from the LPLand returns to the liver binding to the LDL-receptor (LDL-R) via the apoEon the VLDL. VLDL50VLDLLPLApo ELDL-receptor, LDL-R

VLDL6~12

VLDL30IDL

If the VLDL attached to the adipocyte stays attached longer or attachesto another adipocyte and depletesthe triglyceride to 30% the lipoprotein becomes an IDLmolecule which is triglyceride depleted and thus has more percent cholesterol ester.VLDL30IDL

LPLCETPVLDL(IDL)

As more and more triglycerides are removed from the VLDL because of the action ofLPLand CETP enzymes, the composition of the molecule changes, and it becomes intermediate-density lipoprotein (IDL).

VLDLis a large, triglyceride-rich lipoprotein secreted by the liver that transports triglyceride to adipose tissue and muscle. VLDLThe triglycerides in VLDL are removed in capillaries by the enzymelipoprotein lipase, and the VLDL returns to the circulation as a smaller particle with a new name, intermediate-density lipoprotein (IDL). VLDLVLDLIDL

IDL

If the VLDL attached to the adipocyte stays attached longer or attachesto another adipocyte and depletesthe triglyceride to 30% the lipoprotein becomes an IDLmolecule which is triglyceride depleted and thus has more percent cholesterol ester.VLDL30IDL

(Intermediate-density lipoprotein, IDL)

VLDL

(Intermediate-density lipoprotein, IDL)

Intermediate-density lipoproteins(IDLs) belong to thelipoproteinparticle family and are formed from the degradation ofvery low-density lipoproteins.Intermediate-density lipoprotein, LDL

IDLVLDLLDLVLDLLDL

IDLVLDLLDL


IDLVLDLLDLVLDLLDL

VLDLLDL()


IDLVLDLLDLVLDLLDL

IDL2535

Their size is, in general, 25 to 35nm in diameter, and they contain primarily a range oftriacylglycerolsandcholesterolesters. 2535

IDL

IDL(cholesteryl ester)

The IDL particles have lost most of their triglyceride, but they retaincholesteryl esters. IDLSome of the IDL particles are rapidly taken up by the liver; others remain in circulation, where they undergo further triglyceride hydrolysis and are converted to LDL. IDL;LDL

IDL(receptor-mediated endocytosis)LDL(50%)

They are cleared from theplasmainto theliverbyreceptor-mediated endocytosis, or further degraded to formLDL particles.IDL(receptor-mediated endocytosis)LDL(50%)IDL50%IDLLDL

50%IDLApo B-100ApoE

The IDL particles have lost most of their triglyceride, but they retaincholesteryl esters. IDLSome of the IDL particles are rapidly taken up by the liver; others remain in circulation, where they undergo further triglyceride hydrolysis and are converted to LDL. IDL;LDL==================================================================================================Fifty percent of IDLs are recognized by receptors in the liver cells because of theapolipoprotein B-100(apoB-100) and apoE they contain and areendocytosed.

The IDLis taken up by the liver by the LDL-R via apoE.

50%(triglyceride hydrolysis)Apo E

(triglyceride hydrolysis)LDL

LDL(ApoB-100)

(triglyceride hydrolysis)LDL

The other 50% of IDL lose apoE; when their cholesterol content becomes greater than the content of triglyceride, they become LDL, with apoB-100 as the primary apolipoprotein.

IDLcan also rebindto adipocytes to deplete itself more of its triglyceride to ~ 10% where the IDLloses the apoEand apoCperipheral apoproteinsand becomes a cholesterol ester rich LDL molecule with only one apoB100apoproteinper LDL molecule.

LDLLDL(LDL receptor)(endocytosis)LDL

The LDL is taken into a cell via the LDL receptor via endocytosis, where the contents are either stored, used for cell membrane structure, or converted into other products such as steroid hormones or bile acids.

(low-density lipoprotein, LDL)

VLDL

(low-density lipoproteinLDL)(high-density lipoproteinHDL)

(Very-low-density lipoprotein, VLDL)

LDLVLDLApo B100 VLDLLDL

So LDL looks similar to VLDL with a single apoB100apoprotein but unlike the VLDL that is triglyceride rich the LDL is cholesterol ester rich and is the MAIN carrier lipoprotein to transport cholesterol via its ester to the liver and other cells throughout the body.LDLVLDLLDLApo B100VLDLLDL

B-100(4536)

LDLApo EApo CLDL-RApo E

Importantly the LDL molecule does not have apoEor apoCand is therefore not cleared from the blood by the liver as the LDL-R has high affinity for the apoE. ECLDL-RE

The apoB100in LDL has a much lower affinity for the LDL-R on the hepatocytes and as a result the life of LDL in the blood is much longer than all the other lipoproteins like VLDL; IDLboth of which have apoE to bind the LDL-R on the liver cell.LDLApo B100LDL-R1/2LDLVLDLLDL;Apo ELDL-R

LDLApo B100LDL-R1/2LDLVLDLLDL;Apo ELDL-R

Importantly the LDL molecule does not have apoEor apoCand is therefore not cleared from the blood by the liver as the LDL-R has high affinity for the apoE. ECLDL-RE

The apoB100in LDL has a much lower affinity for the LDL-R on the hepatocytes and as a result the life of LDL in the blood is much longer than all the other lipoproteins like VLDL; IDLboth of which have apoE to bind the LDL-R on the liver cell.LDLApo B100LDL-R1/2LDLVLDLLDL;Apo ELDL-R

1/2LDL

The consequence of the long life of LDL in the plasma is the LDL is susceptible to oxidative modification of the phospholipid monolayer containing polyunsaturated fatty acids.LDL

LDLLDL()LDL

This is where the MISNOMER arises with LDL labelled as the BAD cholesterol.LDL is just the main carrier of cholesterol required by all cells in the body. It is NOT the cholesterol that is atherogenic (causing atherosclerosis), it is the damaged oxidized LDL lipoprotein that is taken up by macrophages in the sub endothelial space of the arterial lining. LDLLDLLDL

LDLLDL

Theproblem is that LDL is our carrier of cholesterol and so high LDL particularly when oxidized is directly associated with high risk for vascular disease.LDLLDL

LDL()

LDL (the main cholesterol rich) lipoprotein and if it spends too long in the circulation by poor hepatic uptake tends to oxidize. The polyunsaturated fatty acids (PUFA) in its membrane get damaged by free radicals, and then they proceed to damage the protein in the surface, and finally the fatty acidsin the core.LDLLDLPUFA

LDL(PUFA)

LDL (the main cholesterol rich) lipoprotein and if it spends too long in the circulation by poor hepatic uptake tends to oxidize. The polyunsaturated fatty acids (PUFA) in its membrane get damaged by free radicals, and then they proceed to damage the protein in the surface, and finally the fatty acidsin the core.LDLLDLPUFA

LDL()

Once LDL oxidizes, it can invade the arterial wall in areas that experience disturbed blood flow (turbulence), like the points where arteries curve or branch. These areas are permeable to large molecules. Oxidized LDL attracts immunocompetent white blood cells (to repair the artery) and initiate an inflammatory cascade that produces the unstable arterial plaque. This is the basis of the oxidized LDL theory of atherosclerosis.LDLLDLLDL

LDL()LDL

Once LDL oxidizes, it can invade the arterial wall in areas that experience disturbed blood flow (turbulence), like the points where arteries curve or branch. These areas are permeable to large molecules. Oxidized LDL attracts immunocompetent white blood cells (to repair the artery) and initiate an inflammatory cascade that produces the unstable arterial plaque. This is the basis of the oxidized LDL theory of atherosclerosis.LDLLDLLDL

LDLLDL

LDL2003

:ILDL(26) LDL(B)A

19.0-20.5nmA20.6-22nmB

Large LDL particles measure around 27 nm in diameter, while small LDL particles measure around 24 nm.

LDL

smaller LDL particles having greater triglyceride content and less cholesterol.LDL

( buoyant )LDL


LDLLDL LDL


BLDL

--Are not cleared from the bloodstream as rapidly as the more normal large LDL particles, since the LDL receptor recognizes them less effectively. --AreLDLLDL

Small LDL of pattern B therefore hang around much longer, providing more opportunity to cause atherosclerotic plaque.

BLDL

--Are moreadherentto the artery wall, making them more likely to trigger plaque formation.--Are

LDL

--Are more potent triggers ofinflammatoryresponses of the sort that make atherosclerotic plaque grow.--Are

LDL

--Are more prone tooxidation, making them more powerful triggers of inflammation.--Are

LDLB

--Are more prone toglycation, or the glucose-triggered modification of the apoprotein B that makes it much more likely to contribute to atherosclerotic plaque.--AreB

glycation

Pattern ABPattern B3Pattern A

LDLPattern APattern B3LDLPattern APattern B

Pattern BHDLLDL

(polyacrylamide gradient gel electrophoresis)LDLALDLB

A special blood test called polyacrylamide gradient gel electrophoresis can measure particle size and determine whether a person has blood cholesterol LDL pattern A or LDL pattern B.

LDLALDLB

B(postprandial hyperlipidemia )

Individuals with pattern B are also more likely to develop high blood triglyceride levels after a fatty meal (postprandial hyperlipidemia). B()

B35LDLB

Pattern B is associated with accelerated atherosclerosis and a 3 to 5- fold increase in heart attack risk. B35

Pattern B is believed to be the most important cause of atherosclerosis in people with normal or near normal total and LDL cholesterol levels.LDLB

LDL

Some scientists believe that the smaller LDL particles are more dangerous than the larger ones because they can more easily squeeze through the tiny gaps between the cells in the endothelium to reach inside the artery walls. LDL

The endothelium is a thin layer of cells which covers the inner wall of the arteries. The cells making up the endothelium have tiny gaps between them.

LDL

Others postulate that the smaller LDL cholesterol particles are more easily oxidized. LDLOxidation of cholesterol is significant in the formation of cholesterol plaques.

Freidewald(HDL) LDL-C TC (Total Cholesterol) HDL-C TG (Triglycerides) 14

LDL

How can LDL cholesterol size be enlarged?LDL

LDLLDL(B)LDLLDLBA

Even though LDL cholesterol particle size is mainly genetically inherited, individuals who have small LDL particles (pattern B) can increase their particle size through diet, exercise, and medications.LDLLDLB

Diets that are low in saturated fat and cholesterol, regular aerobic exercise, and loss of excess body fat have been determined to decrease the number of small LDL particles and increase the number of large LDL particles in the blood. LDLLDLIn other words, lifestyle modifications can change pattern B to pattern A.BA

LDLLDL(Lopid)LDL

When lifestyle changes alone are unsuccessful, medications can be used. Even though the statin medications (discussed above) are effective in lowering the absolute levels of LDL cholesterol, they appear to have a limited effect on LDL cholesterol size pattern. LDLLDLMedications such as nicotinic acid (niacin) and gemfibrozil (Lopid) have been found effective in many instances in increasing the size of LDL cholesterol particles.LopidLDL

Lp(a)

Lipoprotein (a) (Lp(a)) is an LDL cholesterol particle that is attached to a special protein called apo(a). In large part, a persons level of Lp(a) in the blood is genetically inherited. Lp(a)LDLApo(a)Lp(a)

(a) [Lipoprotein (a) Lp(a)]LDLApo(a)


Lp(a)


Lp(a) (20~30/)Lp(a)LDL/ HDL

Elevated levels of Lp(a) (higher than 20 mg/dl to 30 mg/dl) in the blood are linked to a greater likelihood of atherosclerosis and heart attacks in both men and women. Lp(a) 20~30/

The risk is even more significant if the Lp(a) cholesterol elevation is accompanied by high LDL/HDL ratios.Lp(a)LDL/ HDL

Lp(a)()Lp(a)

Certain diseases are associated with elevated Lp(a) levels. Patients on chronic kidneydialysisand those with nephrotic syndromes (kidney diseases that cause leakage of blood proteins into the urine) tend to have high levels of Lp(a).LpaLpa

Lp(a)Lp(a)Lp(a)Lp(a) Lp(a)Lp(a)

There are many theories as to how Lp(a) causes atherosclerosis although exactly how Lp(a) accumulates cholesterol plaques on the artery walls has not been well defined. Lp(a)Lp(a)Clinical trials conclusively proving that lowering Lp(a) reduces atherosclerosis and the risk of heart attacks have not been conducted. Lp(a)Currently, there is no international standard for determining Lp(a) cholesterol levels and commercial sources of Lp(a) testing may not have the same accuracy as research laboratories. Lp(a) Lp(a)Therefore, specifically measuring and treating elevated Lp(a) cholesterol levels are not widely performed in this country.Lp(a)

Lp(a)

How can Lp(a) cholesterol levels be reduced?Lp(a) ?

Lopid (cholestyramine)Lp(a)

Most lipid-lowering medications such as statins, Lopid, and cholestyramine have a limited effect in lowering Lp(a) cholesterol levels. LopidLp(a)

(Estrogen)Lp(a)20Lp(a)HDL

Estrogen has been shown to lower Lp(a) cholesterol levels by approximately 20% in women with elevated Lp(a) cholesterol. Lp(a)20Lp(a)

Estrogen can also increase HDL cholesterol levels when given to postmenopausal women. HDL

(NiacinNiaspan)Lp(a)30

Additionally, nicotinic acid (Niacin or Niaspan) in high doses has been found to be effective in lowering Lp(a) cholesterol levels by approximately 30%.NiacinNiaspanLp(a)30

(high-density lipoprotein, HDL)

VLDL

(low-density lipoproteinLDL)(high-density lipoproteinHDL)

(High-density lipoproteinHDL)

8131.211.063/

HDLHDL

30%HDL

HDL

HDL is the lipoprotein transporting cholesterol from the tissues back to the liver for excretion into bile for elimination in the bowel but in the small bowel 70% of cholesterol excreted ultimately is reincorporated with diet fat into chylomicronsin the enterocyte to begin the whole process again.HDL70

70

HDL is the lipoprotein transporting cholesterol from the tissues back to the liver for excretion into bile for elimination in the bowel but in the small bowel 70% of cholesterol excreted ultimately is reincorporated with diet fat into chylomicronsin the enterocyte to begin the whole process again.HDL70

HDL()Apo A

HDL is synthesized by the liver cells (and other gastrointestinal cells) and is a unique lipoprotein containing one integral transmembrane apoA apoprotein. HDLApo A

HDL

HDL when synthesized has very little triglyceride or free cholesterol and is essentially empty as its job is to acquire cholesterol from the periphery to transport back to the liver. HDL

HDL when synthesized has very little triglyceride or free cholesterol and is essentially empty as its job is to acquire cholesterol from the periphery to transport back to the liver. HDL

HDL(lecithin-cholesterol-acyl transferase, LCAT) -()

In the circulation the empty HDL acquires an enzyme LCAT(lecithin-cholesterol-acyl transferase). HDLlecithin-cholesterol-acyl transferase, LCAT-LCAT:lecithin cholesterol acyltransferase

-(LCAT)

LCATHDLC2

70%-80%LCAT

LCATHDLHDLVLDLLDLLCAT

LCATHDLHDL3

HDLLCAT

LCATHDLHDLLCATHDL

The HDL with LCATimbedded in its monolayermembrane attachesto any cell binding to the cholesterol esters in the outer layer of the phospholipid bilayer cell membranes and the LCATattachesto the Hydroxy group on the cholesterol ester and extracts the ester from the outer cell membrane into the HDL molecule. LCATHDLHDLLCATHDL

HDLHDLApo A

Thus HDL takes cholesterol from peripheral cells and loads the cholesterol ester into the HDL and transports this back to the liver attaching to the apoA-receptor on the liver cell for the cholesterol to be synthesized in bile.HDLHDLApo A

HDL()

So in deficient HDL (low HDL) states there is less of this carrier molecule to unload the cells and arterial wall of cholesterol content hence an independent risk for vascular disease. HDL

Like LDL you can equally understand the MISNOMER of HDL being good cholesterol as low levels potentiate vascular disease whilst high HDL tends to protect against atherosclerosis BUT it is NOT cholesterol that is implicated; it is the carrier molecule HDL.LDL;HDL

HDLHDLHDLHDL

HDL(60mg/dL)HDL(40 mg/dL50 mg/dL)

FraminghamLDLHDLHDLLDL

LDL 1 mg/dl , 1 % LDL-C HDL 1 mg/dl , 3 % HDL-C,

LDL: 1 mg/dl , 1 % LDL-CHDL : 1 mg/dl , 3 % HDL-C,

5.Omega-3

6.3035%

Omega-3Omega-6

Omega-3Omega-6

HDLHDL

Much has been made of the reverse cholesterol transport mechanism whereby HDL extracts cholesterol from arterial plaques, but HDL has other importance roles in atherosclerosis with its antioxidant and anti-inflammatory properties key to the protective effect of HDL.HDLHDL

Back-ups

Manyenzymes,transporters, structural proteins,antigens,adhesins, andtoxinsare lipoproteins.

Examples include theplasma lipoprotein particlesclassified underhigh-density(HDL) andlow-density(LDL) lipoproteins, which enable fats to be carried in thebloodstream, thetransmembrane proteinsof themitochondrionand thechloroplast, and bacterial lipoproteins.A core of fats (triglycerides), cholesterol esters (cholesterol linked to fatty acids), and fat-soluble vitamins.A monolayer membrane of phospholipids and small amounts of free cholesterol.Proteins called apoprotein which may be integral apoproteins (apoA or apoB) penetrating as a transmembrane protein through the monolayermembrane, compared to the peripheral apoproteins (apoCor apoE) that are on the outer surface of the phospholipid membrane.A core of fats (triglycerides), cholesterol esters (cholesterol linked to fatty acids), and fat-soluble vitamins.A monolayer membrane of phospholipids and small amounts of free cholesterol.Proteins called apoprotein which may be integral apoproteins (apoA or apoB) penetrating as a transmembrane protein through the monolayermembrane, compared to the peripheral apoproteins (apoCor apoE) that are on the outer surface of the phospholipid membrane.A core of fats (triglycerides), cholesterol esters (cholesterol linked to fatty acids), and fat-soluble vitamins.A monolayer membrane of phospholipids and small amounts of free cholesterol.Proteins called apoprotein which may be integral apoproteins (apoA or apoB) penetrating as a transmembrane protein through the monolayermembrane, compared to the peripheral apoproteins (apoCor apoE) that are on the outer surface of the phospholipid membrane.(Apoprotein/Apolipoprotein)1. marker2. 3. A core of fats (triglycerides), cholesterol esters (cholesterol linked to fatty acids), and fat-soluble vitamins.A monolayer membrane of phospholipids and small amounts of free cholesterol.Proteins called apoprotein which may be integral apoproteins (apoA or apoB) penetrating as a transmembrane protein through the monolayermembrane, compared to the peripheral apoproteins (apoCor apoE) that are on the outer surface of the phospholipid membrane.A core of fats (triglycerides), cholesterol esters (cholesterol linked to fatty acids), and fat-soluble vitamins.A monolayer membrane of phospholipids and small amounts of free cholesterol.Proteins called apoprotein which may be integral apoproteins (apoA or apoB) penetrating as a transmembrane protein through the monolayermembrane, compared to the peripheral apoproteins (apoCor apoE) that are on the outer surface of the phospholipid membrane.The lipid components of lipoproteins are insoluble in water. However, because of their detergent-like (amphipathic) properties, apolipoproteins and other amphipathic molecules (such asphospholipids) can surround the lipids, creating the lipoprotein particle that is itself water-soluble, and can thus be carried through water-based circulation (i.e.,blood,lymph).5 18apoAapoB10048apoCapoDapoEapoJaCETPPTP Chylomicron [.kailu'maikrn]

Chylomicronsare the lipoprotein packages transporting fat from our diet to adipose tissue in our body and the liver. Chylomicronsare the lipoprotein packages transporting fat from our diet to adipose tissue in our body and the liver.

Our intestines package cholesterol, fats, and fat-soluble nutrients and vitamins into chylomicronsin the enterocytecell lining the small intestine. The apoproteinthat these lipoproteins get is apoB-48.Apo B-48Chylomicronsare the lipoprotein packages transporting fat from our diet to adipose tissue in our body and the liver.

Our intestines package cholesterol, fats, and fat-soluble nutrients and vitamins into chylomicronsin the enterocytecell lining the small intestine. The apoproteinthat these lipoproteins get is apoB-48.Apo B-481.2.3.4.5.6.7.8.9.10.11.12.13.Chylomicrons enter the lymphatic circulation and make their way via the thoracic lymph duct to the circulation where the duct empties into the subclavian vein in the neck.

The chylomicronstravel either to the liver or adipose tissue. In the blood stream the chylomicronsacquire two new apoproteins, both peripheral apoproteins; apoCand apoE. ;EEThe chylomicronwill also bind preferentially to adipocytes via the apoClipoprotein to lipoprotein lipase(LPL) an enzyme on the surface of the adipocyte. C(lipoprotein lipase, LPL)

The LPLcleaves the triglycerides in the chylomicronand the glycerol and free fatty acids enter the adipocyte thus depleting the chylomicronof triglyceride content and filling the fat cell with fatty acids. LPL

When triglyceride is reduced to ~ 20% in the chylomicronthe apoCdissociates from the chylomicronand this reduced triglyceride lipoprotein with only apoB48and apoE is now called a chylomicron remnant.20CB 48E (chylomicron remnant)The chylomicronremnant is cleared from the circulation by the liver cell (hepatocytes) via the chylomicronremnant receptor on the hepatocytes, binding to the apoE on the remnant particle. The liver then makes use of the remaining triglyceride.ApoE(chylomicronremnant receptor)The chylomicronstravel either to the liver or adipose tissue. VLDL

The chylomicronstravel either to the liver or adipose tissue. The chylomicronstravel either to the liver or adipose tissue. The chylomicronstravel either to the liver or adipose tissue. VLDL carries mainly triglyceride and cholesterol ester (see table above) and the each VLDL containing one apoB100integral apoproteinin the monolayer membrane.Nascent ,, lipoprteinlipaseLPL

Again identical to chylomicronsthe VLDL binds the adipocyte via the apoCto LPL on the adipocyte with the enzyme cleaving the triglyceride to glycerol and fatty acids to be used by the adipocyte.VLDLCLPL

Once in circulation, VLDL will come in contact withlipoprotein lipase(LPL) in the capillary beds in the body (adipose, cardiac, and skeletal muscle). LPL will remove triglycerides from VLDL for storage or energy production. VLDL now meets back up with HDL where apoC-II is transferred back to HDL (but keeps apoE). HDL also transfers cholesteryl esters to the VLDL in exchange for phospholipids and triglycerides viacholesterylester transfer protein(CETP). VLDL now meets back up with HDL where apoC-II is transferred back to HDL (but keeps apoE). HDL also transfers cholesteryl esters to the VLDL in exchange for phospholipids and triglycerides viacholesterylester transfer protein(CETP). VLDL now meets back up with HDL where apoC-II is transferred back to HDL (but keeps apoE). HDL also transfers cholesteryl esters to the VLDL in exchange for phospholipids and triglycerides viacholesterylester transfer protein(CETP). As the triglyceride in the VLDL drops to 50% the VLDL dissociates from the LPLand returns to the liver binding to the LDL-receptor (LDL-R) via the apoEon the VLDL. VLDL50VLDLLPLApo ELDL-receptor, LDL-RIf the VLDL attached to the adipocyte stays attached longer or attachesto another adipocyte and depletesthe triglyceride to 30% the lipoprotein becomes an IDLmolecule which is triglyceride depleted and thus has more percent cholesterol ester.VLDL30IDLAs more and more triglycerides are removed from the VLDL because of the action ofLPLand CETP enzymes, the composition of the molecule changes, and it becomes intermediate-density lipoprotein (IDL).

VLDLis a large, triglyceride-rich lipoprotein secreted by the liver that transports triglyceride to adipose tissue and muscle. VLDLThe triglycerides in VLDL are removed in capillaries by the enzymelipoprotein lipase, and the VLDL returns to the circulation as a smaller particle with a new name, intermediate-density lipoprotein (IDL). VLDLVLDLIDLIf the VLDL attached to the adipocyte stays attached longer or attachesto another adipocyte and depletesthe triglyceride to 30% the lipoprotein becomes an IDLmolecule which is triglyceride depleted and thus has more percent cholesterol ester.VLDL30IDLVLDL


IDLVLDLLDLVLDLLDLIntermediate-density lipoproteins(IDLs) belong to thelipoproteinparticle family and are formed from the degradation ofvery low-density lipoproteins.Intermediate-density lipoprotein, LDL

IDLVLDLLDLVLDLLDLIntermediate-density lipoproteins(IDLs) belong to thelipoproteinparticle family and are formed from the degradation ofvery low-density lipoproteins.Intermediate-density lipoprotein, LDL

IDLVLDLLDLVLDLLDLTheir size is, in general, 25 to 35nm in diameter, and they contain primarily a range oftriacylglycerolsandcholesterolesters. 2535

IDLThe IDL particles have lost most of their triglyceride, but they retaincholesteryl esters. IDLSome of the IDL particles are rapidly taken up by the liver; others remain in circulation, where they undergo further triglyceride hydrolysis and are converted to LDL. IDL;LDLThey are cleared from theplasmainto theliverbyreceptor-mediated endocytosis, or further degraded to formLDL particles.IDL(receptor-mediated endocytosis)LDL(50%)IDL50%IDLLDLThe IDL particles have lost most of their triglyceride, but they retaincholesteryl esters. IDLSome of the IDL particles are rapidly taken up by the liver; others remain in circulation, where they undergo further triglyceride hydrolysis and are converted to LDL. IDL;LDL==================================================================================================Fifty percent of IDLs are recognized by receptors in the liver cells because of theapolipoprotein B-100(apoB-100) and apoE they contain and areendocytosed.

The IDLis taken up by the liver by the LDL-R via apoE. (triglyceride hydrolysis)LDL(triglyceride hydrolysis)LDL

The other 50% of IDL lose apoE; when their cholesterol content becomes greater than the content of triglyceride, they become LDL, with apoB-100 as the primary apolipoprotein.

IDLcan also rebindto adipocytes to deplete itself more of its triglyceride to ~ 10% where the IDLloses the apoEand apoCperipheral apoproteinsand becomes a cholesterol ester rich LDL molecule with only one apoB100apoproteinper LDL molecule.

The LDL is taken into a cell via the LDL receptor via endocytosis, where the contents are either stored, used for cell membrane structure, or converted into other products such as steroid hormones or bile acids. VLDL

So LDL looks similar to VLDL with a single apoB100apoprotein but unlike the VLDL that is triglyceride rich the LDL is cholesterol ester rich and is the MAIN carrier lipoprotein to transport cholesterol via its ester to the liver and other cells throughout the body.LDLVLDLLDLApo B100VLDLLDLImportantly the LDL molecule does not have apoEor apoCand is therefore not cleared from the blood by the liver as the LDL-R has high affinity for the apoE. ECLDL-RE

The apoB100in LDL has a much lower affinity for the LDL-R on the hepatocytes and as a result the life of LDL in the blood is much longer than all the other lipoproteins like VLDL; IDLboth of which have apoE to bind the LDL-R on the liver cell.LDLApo B100LDL-R1/2LDLVLDLLDL;Apo ELDL-RImportantly the LDL molecule does not have apoEor apoCand is therefore not cleared from the blood by the liver as the LDL-R has high affinity for the apoE. ECLDL-RE

The apoB100in LDL has a much lower affinity for the LDL-R on the hepatocytes and as a result the life of LDL in the blood is much longer than all the other lipoproteins like VLDL; IDLboth of which have apoE to bind the LDL-R on the liver cell.LDLApo B100LDL-R1/2LDLVLDLLDL;Apo ELDL-RThe consequence of the long life of LDL in the plasma is the LDL is susceptible to oxidative modification of the phospholipid monolayer containing polyunsaturated fatty acids.LDLThis is where the MISNOMER arises with LDL labelled as the BAD cholesterol.LDL is just the main carrier of cholesterol required by all cells in the body. It is NOT the cholesterol that is atherogenic (causing atherosclerosis), it is the damaged oxidized LDL lipoprotein that is taken up by macrophages in the sub endothelial space of the arterial lining. LDLLDLLDLTheproblem is that LDL is our carrier of cholesterol and so high LDL particularly when oxidized is directly associated with high risk for vascular disease.LDLLDLLDL (the main cholesterol rich) lipoprotein and if it spends too long in the circulation by poor hepatic uptake tends to oxidize. The polyunsaturated fatty acids (PUFA) in its membrane get damaged by free radicals, and then they proceed to damage the protein in the surface, and finally the fatty acidsin the core.LDLLDLPUFALDL (the main cholesterol rich) lipoprotein and if it spends too long in the circulation by poor hepatic uptake tends to oxidize. The polyunsaturated fatty acids (PUFA) in its membrane get damaged by free radicals, and then they proceed to damage the protein in the surface, and finally the fatty acidsin the core.LDLLDLPUFAOnce LDL oxidizes, it can invade the arterial wall in areas that experience disturbed blood flow (turbulence), like the points where arteries curve or branch. These areas are permeable to large molecules. Oxidized LDL attracts immunocompetent white blood cells (to repair the artery) and initiate an inflammatory cascade that produces the unstable arterial plaque. This is the basis of the oxidized LDL theory of atherosclerosis.LDLLDLLDLOnce LDL oxidizes, it can invade the arterial wall in areas that experience disturbed blood flow (turbulence), like the points where arteries curve or branch. These areas are permeable to large molecules. Oxidized LDL attracts immunocompetent white blood cells (to repair the artery) and initiate an inflammatory cascade that produces the unstable arterial plaque. This is the basis of the oxidized LDL theory of atherosclerosis.LDLLDLLDL Large LDL particles measure around 27 nm in diameter, while small LDL particles measure around 24 nm.smaller LDL particles having greater triglyceride content and less cholesterol.LDLsmaller LDL particles having greater triglyceride content and less cholesterol.LDLsmaller LDL particles having greater triglyceride content and less cholesterol.LDL--Are not cleared from the bloodstream as rapidly as the more normal large LDL particles, since the LDL receptor recognizes them less effectively. --AreLDLLDL

Small LDL of pattern B therefore hang around much longer, providing more opportunity to cause atherosclerotic plaque.

BLDL

--Are moreadherentto the artery wall, making them more likely to trigger plaque formation.--Are--Are more potent triggers ofinflammatoryresponses of the sort that make atherosclerotic plaque grow.--Are--Are more prone tooxidation, making them more powerful triggers of inflammation.--Are--Are more prone toglycation, or the glucose-triggered modification of the apoprotein B that makes it much more likely to contribute to atherosclerotic plaque.--AreB

glycation A special blood test called polyacrylamide gradient gel electrophoresis can measure particle size and determine whether a person has blood cholesterol LDL pattern A or LDL pattern B.

LDLALDLBIndividuals with pattern B are also more likely to develop high blood triglyceride levels after a fatty meal (postprandial hyperlipidemia). B()Pattern B is associated with accelerated atherosclerosis and a 3 to 5- fold increase in heart attack risk. B35

Pattern B is believed to be the most important cause of atherosclerosis in people with normal or near normal total and LDL cholesterol levels.LDLBSome scientists believe that the smaller LDL particles are more dangerous than the larger ones because they can more easily squeeze through the tiny gaps between the cells in the endothelium to reach inside the artery walls. LDL

The endothelium is a thin layer of cells which covers the inner wall of the arteries. The cells making up the endothelium have tiny gaps between them. Others postulate that the smaller LDL cholesterol particles are more easily oxidized. LDLOxidation of cholesterol is significant in the formation of cholesterol plaques.How can LDL cholesterol size be enlarged?LDLEven though LDL cholesterol particle size is mainly genetically inherited, individuals who have small LDL particles (pattern B) can increase their particle size through diet, exercise, and medications.LDLLDLB

Diets that are low in saturated fat and cholesterol, regular aerobic exercise, and loss of excess body fat have been determined to decrease the number of small LDL particles and increase the number of large LDL particles in the blood. LDLLDLIn other words, lifestyle modifications can change pattern B to pattern A.BAWhen lifestyle changes alone are unsuccessful, medications can be used. Even though the statin medications (discussed above) are effective in lowering the absolute levels of LDL cholesterol, they appear to have a limited effect on LDL cholesterol size pattern. LDLLDLMedications such as nicotinic acid (niacin) and gemfibrozil (Lopid) have been found effective in many instances in increasing the size of LDL cholesterol particles.LopidLDLLipoprotein (a) (Lp(a)) is an LDL cholesterol particle that is attached to a special protein called apo(a). In large part, a persons level of Lp(a) in the blood is genetically inherited. Lp(a)LDLApo(a)Lp(a)Lipoprotein (a) (Lp(a)) is an LDL cholesterol particle that is attached to a special protein called apo(a). In large part, a persons level of Lp(a) in the blood is genetically inherited. Lp(a)LDLApo(a)Lp(a)Lipoprotein (a) (Lp(a)) is an LDL cholesterol particle that is attached to a special protein called apo(a). In large part, a persons level of Lp(a) in the blood is genetically inherited. Lp(a)LDLApo(a)Lp(a)Elevated levels of Lp(a) (higher than 20 mg/dl to 30 mg/dl) in the blood are linked to a greater likelihood of atherosclerosis and heart attacks in both men and women. Lp(a) 20~30/

The risk is even more significant if the Lp(a) cholesterol elevation is accompanied by high LDL/HDL ratios.Lp(a)LDL/ HDLCertain diseases are associated with elevated Lp(a) levels. Patients on chronic kidneydialysisand those with nephrotic syndromes (kidney diseases that cause leakage of blood proteins into the urine) tend to have high levels of Lp(a).LpaLpaThere are many theories as to how Lp(a) causes atherosclerosis although exactly how Lp(a) accumulates cholesterol plaques on the artery walls has not been well defined. Lp(a)Lp(a)Clinical trials conclusively proving that lowering Lp(a) reduces atherosclerosis and the risk of heart attacks have not been conducted. Lp(a)Currently, there is no international standard for determining Lp(a) cholesterol levels and commercial sources of Lp(a) testing may not have the same accuracy as research laboratories. Lp(a) Lp(a)Therefore, specifically measuring and treating elevated Lp(a) cholesterol levels are not widely performed in this country.Lp(a) How can Lp(a) cholesterol levels be reduced?Lp(a) ?Most lipid-lowering medications such as statins, Lopid, and cholestyramine have a limited effect in lowering Lp(a) cholesterol levels. LopidLp(a)Estrogen has been shown to lower Lp(a) cholesterol levels by approximately 20% in women with elevated Lp(a) cholesterol. Lp(a)20Lp(a)

Estrogen can also increase HDL cholesterol levels when given to postmenopausal women. HDLAdditionally, nicotinic acid (Niacin or Niaspan) in high doses has been found to be effective in lowering Lp(a) cholesterol levels by approximately 30%.NiacinNiaspanLp(a)30VLDL

HDL is the lipoprotein transporting cholesterol from the tissues back to the liver for excretion into bile for elimination in the bowel but in the small bowel 70% of cholesterol excreted ultimately is reincorporated with diet fat into chylomicronsin the enterocyte to begin the whole process again.HDL70HDL is the lipoprotein transporting cholesterol from the tissues back to the liver for excretion into bile for elimination in the bowel but in the small bowel 70% of cholesterol excreted ultimately is reincorporated with diet fat into chylomicronsin the enterocyte to begin the whole process again.HDL70HDL is synthesized by the liver cells (and other gastrointestinal cells) and is a unique lipoprotein containing one integral transmembrane apoA apoprotein. HDLApo AHDL when synthesized has very little triglyceride or free cholesterol and is essentially empty as its job is to acquire cholesterol from the periphery to transport back to the liver. HDLHDL when synthesized has very little triglyceride or free cholesterol and is essentially empty as its job is to acquire cholesterol from the periphery to transport back to the liver. HDLIn the circulation the empty HDL acquires an enzyme LCAT(lecithin-cholesterol-acyl transferase). HDLlecithin-cholesterol-acyl transferase, LCAT-LCAT:lecithin cholesterol acyltransferase

The HDL with LCATimbedded in its monolayermembrane attachesto any cell binding to the cholesterol esters in the outer layer of the phospholipid bilayer cell membranes and the LCATattachesto the Hydroxy group on the cholesterol ester and extracts the ester from the outer cell membrane into the HDL molecule. LCATHDLHDLLCATHDLThus HDL takes cholesterol from peripheral cells and loads the cholesterol ester into the HDL and transports this back to the liver attaching to the apoA-receptor on the liver cell for the cholesterol to be synthesized in bile.HDLHDLApo ASo in deficient HDL (low HDL) states there is less of this carrier molecule to unload the cells and arterial wall of cholesterol content hence an independent risk for vascular disease. HDL

Like LDL you can equally understand the MISNOMER of HDL being good cholesterol as low levels potentiate vascular disease whilst high HDL tends to protect against atherosclerosis BUT it is NOT cholesterol that is implicated; it is the carrier molecule HDL.LDL;HDLLDL: 1 mg/dl , 1 % LDL-CHDL : 1 mg/dl , 3 % HDL-C, Omega-3Omega-6Much has been made of the reverse cholesterol transport mechanism whereby HDL extracts cholesterol from arterial plaques, but HDL has other importance roles in atherosclerosis with its antioxidant and anti-inflammatory properties key to the protective effect of HDL.HDLHDL

three-hypers series - hyperlipidemia - 03 what are lipoproteins?

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