APOLIPOPROTEINS: WHAT ARE THEY, FUNCTIONS, TYPES - BIOLOGY - 2025

The apolipoproteins are proteins that form part of lipoproteins, which are macromolecular complexes "pseudomicelares" composed of a central or core apolar consisting of triglycerides and cholesterol esters surrounded by a phospholipid layer and lipoproteins and involved in lipid homeostasis.

The blood plasma of a human being has dozens of different apolipoproteins, classified into five main groups: apolipoproteins A, B, C, D and E. Some of these groups can be subdivided according to the presence of variants or isoforms and for this purpose adds a number in roman letters that designates the sub-rating.

Representation of a segment of an Apolipoprotein (Source: Jawahar Swaminathan and MSD staff at the European Bioinformatics Institute via Wikimedia Commons)

Each of these classes of apolipoproteins is associated with a specific type of lipoprotein or lipoprotein particle, and therefore it is necessary to enter into context with some characteristics and definitions of these macromolecular complexes.

Types of lipoproteins

According to the density at which they float by ultracentrifugation, lipoproteins (the complexes to which apolipoproteins belong) are commonly grouped into 6 classes with different properties and functions, namely:

1. Chylomicrons.
2. Chylomicron remnant particles.
3. Very low-density lipoproteins (VLDL).
4. Intermediate density lipoproteins (IDL).
5. Low-density lipoproteins (LDL).
6. High-density lipoproteins (HDL).

Characteristics of lipoproteins

Chylomicrons are the largest lipoproteins, and therefore the least dense. They are synthesized in the intestines and are responsible for the transport of lipids and fats that come from the food we eat.

When the triglycerides inside are hydrolyzed during their transit through the blood plasma, the remaining cholesterol-laden particles are transported for elimination in the liver.

VLDL lipoproteins also transport triglycerides and cholesterol from the liver and contribute to their redistribution in different tissues. When triglycerides are hydrolyzed in blood plasma, smaller particles, IDL and LDL, are formed.

LDLs are the lipoproteins mainly responsible for the transport of cholesterol in plasma. HDL is formed in different places including the liver and the intestine; They are involved in the “reverse” transport of cholesterol ”, as they acquire cholesterol from the tissues and transport it to the liver for excretion.

Functions of apolipoproteins

Apolipoproteins, the main protein components of lipoproteins, have various functions in the metabolism of the lipids they harbor, especially in their regulation.

The varied functions also include the transport and redistribution of lipids between different tissues, which involves the recognition of specific apolipoproteins that act as ligands for special receptors on the surface of target cells.

Apolipoproteins B-100 and E mediate the interaction of LDL lipoproteins with apo B, E (LDL) receptors in hepatic and extrahepatic tissues, and with apoE receptors in the liver, so that they are “taken up” by cells, thus regulating their plasma levels.

At the same time, these apolipoproteins participate in the redistribution of cholesterol between cells, which serves as a structural molecule for membrane biogenesis, as a precursor for steroids, or which is simply eliminated from the body through the liver.

An example of specific functions is the apolipoprotein apo B48, which participates in the formation and assembly of chylomicrons in the intestine. Its defects produce failures in the production of VLDL lipoproteins and chylomicrons, which results in certain pathologies related to essential fatty acids and lipids.

Apolipoproteins are also cofactors for lipid metabolism enzymes, for example lipoprotein lipase, which catalyzes the hydrolysis of triglycerides in chylomicrons, requires the presence of a class C apolipoprotein.

They maintain and stabilize the structure of lipoproteins by interacting with the micellar structure and phospholipids on the surface of lipoprotein particles, providing a hydrophilic surface for their contact with the aqueous medium that surrounds them.

Types

As mentioned above, there are five main types of apolipoproteins, named after the letters of the alphabet A, B, C, D, and E.

Apolipoprotein A (I, II, IV)

Apolipoprotein group A contains classes I, II, and IV. Among them, apolipoprotein AI is the protein component of HDL and can also be found in minute proportions in chylomicrons. It is produced in the intestine and in the liver. Among its main functions is to participate as an enzyme cofactor.

ApoA-II is the second component of HDL particles and can also be found in other lipoproteins. It is also synthesized in the liver and is a dimer that may play a role in regulating the binding of lipoproteins to apoE receptors.

Apolipoprotein B

This group of apolipoproteins is found mainly in chylomicrons, VLDL, IDL and LDL. There are two main forms which are known as apolipoprotein B100 (apoB100) and apolipoprotein B-48 (apoB48).

ApoB100 is synthesized by hepatocytes (liver cells) and is an essential component especially in VLDL, IDL and LDL lipoproteins, while apoB48 is synthesized by enterocytes (intestinal cells) and is restricted to chylomicrons and their remnant particles.

ApoB100 is a complex of several subunits, weighs more than 300 kDa, and is a glycosylated protein. ApoB48 is a protein closely related to apoB100, it is thought to be a fragment of it, but some authors consider that it is the product of the transcription and translation of a different gene.

Apolipoprotein C (I, II, III)

The apolipoproteins CI, C-II and C-III are the protein components of the surface of chylomicrons, and of the lipoproteins VLDL and HDL. They participate in multiple metabolic functions and among them, the redistribution of lipoprotein classes stands out, that is, they are involved in the metabolic remodeling of these structures.

Apolipoprotein E

These proteins participate in the formation of chylomicrons, VLDL and HDL. They have many functions, but perhaps the most important are related to the concentration of cholesterol in the blood and its transport to different tissues or its elimination through the liver.

Many types of diseases are related to defects in this apolipoprotein, either with its synthesis from RNA messengers, due to defects with the factors that regulate its transcription and translation, or directly with its activity or structural conformation.

It has been associated with coronary heart disease, with congenital cholesterol deposition and accumulation defects, and even with neurodegenerative diseases such as Alzheimer's.

References

1. Elliott, DA, Weickert, CS, & Garner, B. (2010). Apolipoproteins in the brain: implications for neurological and psychiatric disorders. Clinical Lipidology, 5 (4), 555–573.
2. Fox, SI (2006). Human Physiology (9th ed.). New York, USA: McGraw-Hill Press.
3. Mahley, RW, Innerarity, TL, Rall, SC, & Weisgarber, KH (1984). Plasma lipoproteins: apolipoprotein structure and function. Journal of Lipid Research, 25, 1277–1294.
4. Rawn, JD (1998). Biochemistry. Burlington, Massachusetts: Neil Patterson Publishers.
5. Smith, JD (2002). Apolipoproteins and aging: emerging mechanisms. Aging Research Reviews, 1, 345–365.