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You are watching: Which of the following lipoproteins contains the highest percentage of cholesterol?

Feingold KR, Anawalt B, Boyce A, et al., editors. Endotext . Southern Dartmouth (MA): MDText.com, Inc.; 2000-.


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ABSTRACT

Cholesterol and triglycerides are insoluble in water and also therefore this lipids should be transported in association through proteins. Lipoproteins are complicated particles through a main core comprise cholesterol esters and triglycerides surrounding by free cholesterol, phospholipids, and apolipoproteins, i beg your pardon facilitate lipoprotein formation and also function. Plasma lipoproteins can be separated into 7 classes based on size, lipid composition, and also apolipoproteins (chylomicrons, chylomicron remnants, VLDL, IDL, LDL, HDL, and also Lp (a)). Chylomicron remnants, VLDL, IDL, LDL, and Lp (a) are all pro-atherogenic while HDL is anti-atherogenic. Apolipoproteins have actually four major functions consisting of 1) serving a structural role, 2) acting together ligands because that lipoprotein receptors, 3) guiding the development of lipoproteins, and 4) serving together activators or inhibitors of enzymes affiliated in the line of lipoproteins. The exogenous lipoprotein pathway starts with the incorporation of diet lipids right into chylomicrons in the intestine. In the circulation, the triglycerides carried in chylomicrons are metabolized in muscle and also adipose tissue by lipoprotein lipase releasing complimentary fatty acids, which space subsequently metabolized through muscle and adipose tissue, and also chylomicron remnants room formed. Chylomicron remnants room then taken up by the liver. The endogenous lipoprotein pathway begins in the liver with the development of VLDL. The triglycerides brought in VLDL room metabolized in muscle and also adipose tissue by lipoprotein lipase releasing cost-free fatty acids and also IDL space formed. The IDL are more metabolized come LDL, which are taken up by the LDL receptor in numerous tissues consisting of the liver, the predominant site of uptake. Reverse cholesterol transport begins with the development of nascent HDL through the liver and intestine. These small HDL particles deserve to then obtain cholesterol and phospholipids that are effluxed native cells, a process mediated through ABCA1 bring about the formation of maturation HDL. Tires HDL can acquire enhancement cholesterol from cells via ABCG1, SR-B1, or passive diffusion. The HDL climate transports the cholesterol to the liver either straight by connecting with hepatic SR-B1 or indirectly by delivering the cholesterol come VLDL or LDL, a procedure facilitated by CETP. Cholesterol efflux indigenous macrophages to HDL plays an essential role in protecting from the development of atherosclerosis. For finish coverage of all related locations of Endocrinology, please visit our on-line complimentary web-text, WWW.ENDOTEXT.ORG.


INTRODUCTION

Because lipids, such as cholesterol and triglycerides, space insoluble in water this lipids need to be transported in association with proteins (lipoproteins) in the circulation. Huge quantities of fat acids indigenous meals should be transported together triglycerides to protect against toxicity. These lipoproteins pat a key role in the absorption and also transport of diet lipids by the small intestine, in the deliver of lipids native the liver come peripheral tissues, and also the carry of lipids native peripheral organization to the liver and also intestine (reverse cholesterol transport). A secondary function is to transport toxic foreign hydrophobic and also amphipathic compounds, such together bacterial endotoxin, from areas of invasion and also infection (1).


STRUCTURE the LIPOPROTEINS (2)

Lipoproteins are facility particles that have a main hydrophobic core of non-polar lipids, mainly cholesterol esters and triglycerides. This hydrophobic core is surrounded by a hydrophilic membrane consist of of phospholipids, cost-free cholesterol, and also apolipoproteins (Figure 1). Plasma lipoproteins are separated into 7 classes based on size, lipid composition, and apolipoproteins (Table 1 and Figure 2).


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LipoproteinDensity (g/ml)Size (nm)Major LipidsMajor Apoproteins
Chylomicrons<0.93075-1200TriglyceridesApo B-48, Apo C, Apo E, Apo A-I, A-II, A-IV
Chylomicron Remnants0.930- 1.00630-80Triglycerides CholesterolApo B-48, Apo E
VLDL0.930- 1.00630-80TriglyceridesApo B-100, Apo E, Apo C
IDL1.006- 1.01925-35Triglycerides CholesterolApo B-100, Apo E, Apo C
LDL1.019- 1.06318- 25CholesterolApo B-100
HDL1.063- 1.2105- 12Cholesterol PhospholipidsApo A-I, Apo A-II, Apo C, Apo E
Lp (a)1.055- 1.085~30CholesterolApo B-100, Apo (a)

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Chylomicrons

These are huge triglyceride affluent particles made by the intestine, i m sorry are affiliated in the transfer of dietary triglycerides and also cholesterol to peripheral tissues and also liver. These particles save apolipoproteins A-I, A-II, A-IV, A-V, B-48, C-II, C-III, and also E. Apo B-48 is the main point structural protein and also each chylomicron particle has one Apo B-48 molecule. The size of chylomicrons varies relying on the amount of fat ingested. A high fat meal leads to the formation of big chylomicron particles due to the boosted amount the triglyceride being transported vice versa, in the fasting state the chylomicron particles are tiny carrying decreased quantities of triglyceride.


Chylomicron Remnants

The removal of triglyceride from chylomicrons through peripheral tissues outcomes in smaller particles referred to as chylomicron remnants. Compared to chylomicrons this particles room enriched in cholesterol and are pro-atherogenic.


Very Low-Density Lipoproteins (VLDL)

These particles are created by the liver and also are triglyceride rich. Castle contain apolipoprotein B-100, C-I, C-II, C-III, and also E. Apo B-100 is the core structural protein and each VLDL particle has one Apo B-100 molecule. Similar to chylomicrons the dimension of the VLDL particles have the right to vary relying on the amount of triglyceride brought in the particle. Once triglyceride production in the liver is increased, the secreted VLDL particles are large. However, VLDL corpuscle are smaller sized than chylomicrons.


Intermediate-Density Lipoproteins (IDL; VLDL Remnants)

The removed of triglythrade from VLDL by muscle and adipose tissue results in the development of IDL particles which space enriched in cholesterol. This particles save apolipoprotein B-100 and E. This IDL particles room pro-atherogenic.


Low-Density Lipoproteins (LDL)

These particles are obtained from VLDL and also IDL particles and they are also further enriched in cholesterol. LDL dead the bulk of the cholesterol the is in the circulation. The predominant apolipoprotein is B-100 and each LDL particle includes one Apo B-100 molecule. LDL is composed of a spectrum that particles differing in size and density. An abundance of small dense LDL particles are seen in association v hypertriglyceridemia, low HDL levels, obesity, type 2 diabetes (i.e. Patients through the metabolic syndrome) and infectious and also inflammatory states. These small dense LDL corpuscle are considered to be an ext pro-atherogenic than big LDL particles because that a variety of reasons. Tiny dense LDL particles have actually a lessened affinity because that the LDL receptor resulting in a prolonged retention time in the circulation. Additionally, they an ext easily enter the arterial wall surface and bind an ext avidly to intra-arterial proteoglycans, i m sorry traps castle in the arterial wall. Finally, tiny dense LDL corpuscle are an ext susceptible to oxidation, which could an outcome in an intensified uptake by macrophages.


High-Density Lipoproteins (HDL)

These particles play crucial role in turning back cholesterol transport from peripheral organization to the liver, i m sorry is one potential mechanism whereby HDL might be anti-atherogenic. In addition, HDL particles have anti-oxidant, anti-inflammatory, anti-thrombotic, and anti-apoptotic properties, i beg your pardon may additionally contribute come their capability to inhibit atherosclerosis. HDL particles are enriched in cholesterol and phospholipids. Apolipoproteins A-I, A-II, A-IV, C-I, C-II, C-III, and also E are associated with these particles. Apo A-I is the core structural protein and also each HDL particle may contain many Apo A-I molecules. HDL particles are really heterogeneous and also can be classified based on density, size, charge, or apolipoprotein ingredient (Table 2).


Table 2.


Classification the HDL


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Method that classificationTypes that HDL
Density gradient ultracentrifugationHDL2, HDL3, really high-density HDL
Nuclear magnetic resonancelarge, medium, and small
Gradient gel electrophoresisHDL 2a, 2b, 3a, 3b, 3c
2-dimensional gelatin electrophoresispre-beta 1 and 2, alpha 1, 2, 3, 4
Apolipoprotein compositionA-I particles, A-I: A-II particles, A-I: E particles

Lipoprotein (a) (Lp (a))

Lp (a) is one LDL bit that has actually apolipoprotein (a) attached to Apo B-100 via a de defiders bond. This bit is pro-atherogenic. The physiologic function of this lipoprotein is unknown.


APOLIPOPROTEINS (3,4)

Apolipoproteins have four significant functions including 1) offer a structural role, 2) acting together ligands because that lipoprotein receptors, 3) guiding the development of lipoproteins, and also 4) serving as activators or inhibitors of enzymes affiliated in the metabolism of lipoproteins (Table 3). Apolipoproteins for this reason play a an important role in lipoprotein metabolism.


Apolipoprotein A-I

Apo A-I is synthesized in the liver and intestine and is the major structural protein of HDL accounting for around 70% that HDL protein. It likewise plays a role in the interaction of HDL v ATP-binding cassette protein A1 (ABCA1), ABCG1, and also class B, form I scavenger receptor (SR-B1). Apo A-I is one activator that lecithin: cholesterol acyltransferase (LCAT), an enzyme that converts complimentary cholesterol into cholesteryl ester. High level of Apo A-I is connected with a reduced risk of atherosclerosis.


Apolipoprotein A-II

Apo A-II is synthesized in the liver and also is the second most plentiful protein on HDL audit for about 20% of HDL protein. The function of Apo A-II in lipid line is unclear. Apo A-II is a solid predictor of risk for CVD.


Apolipoprotein A-IV (5)

Apo A-IV is synthesized in the intestine throughout fat absorption. Apo A-IV is associated with chylomicrons and also high-density lipoproteins, however is additionally found in the lipoprotein-free fraction. Its specific role in lipoprotein metabolism continues to be to be determined yet studies have argued a function for Apo A-IV in regulation food intake.


Apolipoprotein A-V (6)

Apo A-V is synthesized in the liver and associates with triglyceride wealthy lipoproteins. It is one activator that LPL mediated lipolysis and thereby plays an important role in the line of triglyceride well-off lipoproteins.


Apolipoprotein B-48

Apo B-48 is synthesized in the intestine and also is the major structural protein of chylomicrons and also chylomicron remnants. Over there is a solitary molecule that apo B-48 per chylomicron particle. There is a solitary apolipoprotein B gene the is to express in both the liver and also intestine. The intestine expresses a protein that is approximately ½ the size of the liver because of mRNA editing. The apobec-1 editing facility is express in the intestine and edits a specific cytidine to an uracil in the apo B mRNA in the intestine creating a protect against codon that outcomes in the cessation that protein translation and also a shorter Apo B (Apo B-48). Especially Apo B-48 is not well-known by the LDL receptor.


Apolipoprotein B-100

Apo B-100 is synthesized in the liver and is the major structural ingredient of VLDL, IDL, and LDL. There is a solitary molecule of Apo B-100 every VLDL, IDL, and LDL particle. Apo B-100 is a ligand because that the LDL receptor and also therefore plays an important role in the clearance that lipoprotein particles. High level of Apo B-100 is associated with an raised risk that atherosclerosis.


Apolipoprotein C (7,8)

The C apolipoproteins space synthesized primarily in the liver and freely exchange in between lipoprotein particles and also therefore are uncovered in association v chylomicrons, VLDL, and also HDL.

Apo C-II is a co-factor because that lipoprotein lipase (LPL) and thus stimulates triglyceride hydrolysis (7). Loss of duty mutations in Apo C-II result in significant hypertriglyceridemia as result of a fail to metabolize triglyceride rich lipoproteins.

Apo C-III is an inhibitor of LPL (9). Additionally, Apo C-III inhibits the interaction of triglyceride affluent lipoproteins through their receptors. Recent studies have shown that ns of role mutations in Apo C-III result in decreases in serum triglyceride levels and a lessened risk of cardiovascular disease. Interestingly, inhibition that Apo C-III expression outcomes in a decrease in serum triglyceride levels also in patient deficient in lipoprotein lipase indicating that the ability of Apo C-III come modulate serum triglyceride levels is no dependent exclusively on regulation lipoprotein lipase activity.


Apolipoprotein E (10)

Apolipoprotein E is synthesized in plenty of tissues but the liver and also intestine are the primary source of circulating Apo E. Apo E exchanges in between lipoprotein particles and also is linked with chylomicrons, chylomicron remnants, VLDL, IDL, and a subgroup that HDL particles. There are three usual genetic variants that Apo E (Apo E2, E3, and also E4). ApoE2 different from the most usual isoform, Apo E3, by a solitary amino mountain substitution where cysteine substitutes for arginine in ~ residue 158. Apo E4 different from Apo E3 in ~ residue 112, whereby arginine substitutes because that cysteine. Apo E3 and also E4 are ligands for the LDL receptor if Apo E2 is poorly recognized by the LDL receptor. Patient who room homozygous because that Apo E2 can develop familial dysbetalipoproteinemia. Apo E4 is associated with an raised risk that Alzheimer’s disease and an boosted risk of atherosclerosis.


Apolipoprotein (a) (11)

Apo (a) is synthesized in the liver. This protein is a homolog of plasminogen and its molecular weight varies indigenous 300,000 to 800,000. It is attached come Apo B-100 via a de defiders bond. High levels of Apo (a) are connected with an enhanced risk that atherosclerosis. Apo (a) is one inhibitor that fibrinolysis and also can also enhance the absorb of lipoproteins through macrophages, both the which might increase the threat of atherosclerosis. The physiologic function of Apo (a) is unknown. Interesting way this apolipoprotein is uncovered in primates however not in various other species.


Table 3.


Apolipoproteins


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ApolipoproteinMWPrimary SourceLipoprotein AssociationFunction
Apo A-I28,000Liver, IntestineHDL, chylomicronsStructural protein because that HDL, Activates LCAT
Apo A-II17,000LiverHDL, chylomicronsStructural protein for HDL, Activates hepatic lipase
Apo A-IV45,000IntestineHDL, chylomicronsUnknown
Apo A-V39,000LiverVLDL, chylomicrons, HDLPromotes LPL mediated TG lipolysis
Apo B-48241,000IntestineChylomicronsStructural protein because that chylomicrons
Apo B-100512,000LiverVLDL, IDL, LDL, Lp (a)Structural protein, Ligand for LDL receptor
Apo C-I6,600LiverChylomicrons, VLDL, HDLActivates LCAT
Apo C-II8,800LiverChylomicrons, VLDL, HDLCo-factor because that LPL
Apo C-III8,800LiverChylomicrons, VLDL, HDLInhibits LPL and uptake the lipoproteins
Apo E34,000LiverChylomicron remnants, IDL, HDLLigand for LDL receptor
Apo (a)250,000- 800,00LiverLp (a)Inhibits plasminogen activation

LIPOPROTEIN RECEPTORS and also LIPID TRANSPORTERS

There are several receptors and also transporters that play a vital role in lipoprotein metabolism.

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LDL Receptor (12)

The LDL receptor is existing in the liver and also most other tissues. It recognizes Apo B-100 and also Apo E and hence mediates the uptake of LDL, chylomicron remnants, and IDL, which occurs via endocytosis (Figure 3). After internalization, the lipoprotein particle is degraded in lysosomes and the cholesterol is released. The delivery of cholesterol to the cabinet decreases the task of HMGCoA reductase, a vital enzyme in the biosynthesis of cholesterol, and also the expression the LDL receptors. LDL receptor in the liver beat a major role in determining plasma LDL levels (a low variety of receptors is associated with high plasma LDL level while a high variety of hepatic LDL receptor is linked with short plasma LDL levels). The variety of LDL receptor is regulation by the cholesterol contents of the cabinet (13). When cellular cholesterol levels are lessened the transcription aspect SREBP is transported from the endoplasmic reticulum to the golgi whereby proteases cleave and activate SREBP, which then migrates come the nucleus and stimulates the expression that LDL receptors (Figure 4). Conversely, once cellular cholesterol levels space high SREBP stays in the absorbent reticulum in one inactive kind and the expression the LDL receptor is low. As debated later PCSK9 regulates the rate of degradation of LDL receptors.