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A lipoprotein is a
biochemical Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms. A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, ...
assembly whose primary function is to transport
hydrophobic In chemistry, hydrophobicity is the chemical property of a molecule (called a hydrophobe) that is seemingly repelled from a mass of water. In contrast, hydrophiles are attracted to water. Hydrophobic molecules tend to be nonpolar and, thu ...
lipid Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ...
(also known as
fat In nutrition science, nutrition, biology, and chemistry, fat usually means any ester of fatty acids, or a mixture of such chemical compound, compounds, most commonly those that occur in living beings or in food. The term often refers specif ...
) molecules in water, as in
blood plasma Blood plasma is a light Amber (color), amber-colored liquid component of blood in which blood cells are absent, but which contains Blood protein, proteins and other constituents of whole blood in Suspension (chemistry), suspension. It makes up ...
or other
extracellular fluid In cell biology, extracellular fluid (ECF) denotes all body fluid outside the cells of any multicellular organism. Total body water in healthy adults is about 50–60% (range 45 to 75%) of total body weight; women and the obese typically ha ...
s. They consist of a
triglyceride A triglyceride (from '' tri-'' and '' glyceride''; also TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids. Triglycerides are the main constituents of body fat in humans and other vertebrates ...
and
cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...
center, surrounded by a
phospholipid Phospholipids are a class of lipids whose molecule has a hydrophilic "head" containing a phosphate group and two hydrophobic "tails" derived from fatty acids, joined by an alcohol residue (usually a glycerol molecule). Marine phospholipids typ ...
outer shell, with the
hydrophilic A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press. In contrast, hydrophobes are n ...
portions oriented outward toward the surrounding water and
lipophilic Lipophilicity (from Greek language, Greek λίπος "fat" and :wikt:φίλος, φίλος "friendly") is the ability of a chemical compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. Such compounds are c ...
portions oriented inward toward the lipid center. A special kind of protein, called
apolipoprotein Apolipoproteins are proteins that bind lipids (oil-soluble substances such as fats, cholesterol and fat soluble vitamins) to form lipoproteins. They transport lipids in blood, cerebrospinal fluid and lymph. The lipid components of lipoprotei ...
, is embedded in the outer shell, both stabilising the complex and giving it a functional identity that determines its role. Plasma lipoprotein particles are commonly divided into five main classes, based on size, lipid composition, and apolipoprotein content. They are, in increasing size order: HDL,
LDL Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall densit ...
, IDL,
VLDL Very-low-density lipoprotein (VLDL), density relative to extracellular water, is a type of lipoprotein made by the liver. VLDL is one of the five major groups of lipoproteins (chylomicrons, VLDL, intermediate-density lipoprotein, LDL, low-density ...
and
chylomicron Chylomicrons (from the Greek χυλός, chylos, meaning ''juice'' (of plants or animals), and micron, meaning ''small''), also known as ultra low-density lipoproteins (ULDL), are lipoprotein particles that consist of triglycerides (85–92%), ...
s. Subgroups of these plasma particles are primary drivers or modulators of
atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by eleva ...
. Many
enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
s, transporters, structural proteins,
antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
s, adhesins, and
toxin A toxin is a naturally occurring poison produced by metabolic activities of living cells or organisms. They occur especially as proteins, often conjugated. The term was first used by organic chemist Ludwig Brieger (1849–1919), derived ...
s are sometimes also classified as lipoproteins, since they are formed by lipids and proteins.


Scope


Transmembrane lipoproteins

Some transmembrane
proteolipid A proteolipid is a protein covalently linked to lipid molecules, which can be fatty acids, isoprenoids or sterols. The process of such a linkage is known as protein lipidation, and falls into the wider category of acylation and post-translationa ...
s, especially those found in
bacteria Bacteria (; : bacterium) are ubiquitous, mostly free-living organisms often consisting of one Cell (biology), biological cell. They constitute a large domain (biology), domain of Prokaryote, prokaryotic microorganisms. Typically a few micr ...
, are referred to as lipoproteins; they are not related to the lipoprotein particles that this article is about. Such
transmembrane protein A transmembrane protein is a type of integral membrane protein that spans the entirety of the cell membrane. Many transmembrane proteins function as gateways to permit the transport of specific substances across the membrane. They frequently un ...
s are difficult to isolate, as they bind tightly to the lipid membrane, often require lipids to display the proper structure, and can be water-insoluble. Detergents are usually required to isolate transmembrane lipoproteins from their associated biological membranes.


Plasma lipoprotein particles

Because fats are insoluble in water, they cannot be transported on their own in extracellular water, including blood plasma. Instead, they are surrounded by a hydrophilic external shell that functions as a transport vehicle. The role of lipoprotein particles is to transport fat molecules, such as
triglyceride A triglyceride (from '' tri-'' and '' glyceride''; also TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids. Triglycerides are the main constituents of body fat in humans and other vertebrates ...
s, phospholipids, and cholesterol within the extracellular water of the body to all the cells and tissues of the body. The proteins included in the external shell of these particles, called apolipoproteins, are synthesized and secreted into the extracellular water by both the
small intestine The small intestine or small bowel is an organ (anatomy), organ in the human gastrointestinal tract, gastrointestinal tract where most of the #Absorption, absorption of nutrients from food takes place. It lies between the stomach and large intes ...
and
liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...
cells. The external shell also contains phospholipids and cholesterol. All cells use and rely on fats and cholesterol as building blocks to create the multiple
membranes A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. B ...
that cells use both to control internal water content and internal water-soluble elements and to organize their internal structure and protein enzymatic systems. The outer shell of lipoprotein particles have the hydrophilic groups of phospholipids, cholesterol, and apolipoproteins directed outward. Such characteristics make them soluble in the salt-water-based blood pool.
Triglyceride A triglyceride (from '' tri-'' and '' glyceride''; also TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids. Triglycerides are the main constituents of body fat in humans and other vertebrates ...
s and
cholesteryl esters 300px, Cholesteryl oleate, a member of the cholesteryl ester family Cholesteryl esters are a type of dietary lipid and are ester derivatives of cholesterol. The ester bond is formed between the carboxylate group of a fatty acid and the hydroxyl g ...
are carried internally, shielded from the water by the outer shell. The kind of apolipoproteins contained in the outer shell determines the functional identity of the lipoprotein particles. The interaction of these apolipoproteins with enzymes in the blood, with each other, or with specific proteins on the surfaces of cells, determines whether triglycerides and cholesterol will be added to or removed from the lipoprotein transport particles. Characterization in human plasma


Structure

Lipoproteins are complex particles that have a central hydrophobic core of non-polar lipids, primarily cholesteryl esters and triglycerides. This hydrophobic core is surrounded by a hydrophilic membrane consisting of phospholipids, free cholesterol, and apolipoproteins. Plasma lipoproteins, found in
blood plasma Blood plasma is a light Amber (color), amber-colored liquid component of blood in which blood cells are absent, but which contains Blood protein, proteins and other constituents of whole blood in Suspension (chemistry), suspension. It makes up ...
, are typically divided into five main classes based on size, lipid composition, and apolipoprotein content: HDL,
LDL Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall densit ...
, IDL,
VLDL Very-low-density lipoprotein (VLDL), density relative to extracellular water, is a type of lipoprotein made by the liver. VLDL is one of the five major groups of lipoproteins (chylomicrons, VLDL, intermediate-density lipoprotein, LDL, low-density ...
and
chylomicron Chylomicrons (from the Greek χυλός, chylos, meaning ''juice'' (of plants or animals), and micron, meaning ''small''), also known as ultra low-density lipoproteins (ULDL), are lipoprotein particles that consist of triglycerides (85–92%), ...
s.


Functions


Metabolism

The handling of lipoprotein particles in the body is referred to as ''lipoprotein particle metabolism''. It is divided into two pathways,
exogenous In a variety of contexts, exogeny or exogeneity () is the fact of an action or object originating externally. It is the opposite of endogeneity or endogeny, the fact of being influenced from within a system. Economics In an economic model, an ...
and
endogenous Endogeny, in biology, refers to the property of originating or developing from within an organism, tissue, or cell. For example, ''endogenous substances'', and ''endogenous processes'' are those that originate within a living system (e.g. an ...
, depending in large part on whether the lipoprotein particles in question are composed chiefly of dietary (exogenous) lipids or whether they originated in the liver (endogenous), through
de novo synthesis In chemistry, ''de novo'' synthesis () is the synthesis of complex molecules from simple molecules such as sugars or amino acids, as opposed to recycling after partial degradation. For example, nucleotides are not needed in the diet as they can ...
of triglycerides. The
hepatocyte A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, bi ...
s are the main platform for the handling of triglycerides and cholesterol; the liver can also store certain amounts of
glycogen Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. It is the main storage form of glucose in the human body. Glycogen functions as one of three regularly used forms ...
and triglycerides. While
adipocyte Adipocytes, also known as lipocytes and fat cells, are the cell (biology), cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through ...
s are the main storage cells for triglycerides, they do not produce any lipoproteins.


Exogenous pathway

Bile Bile (from Latin ''bilis''), also known as gall, is a yellow-green/misty green fluid produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine. In humans, bile is primarily composed of water, is pro ...
emulsifies fats contained in the
chyme Chyme or chymus (; ) is the semi-fluid mass of partly digested food that is expelled by the stomach, through the pyloric valve, into the duodenum (the beginning of the small intestine). Chyme results from the mechanical and chemical breakdown ...
, then
pancreatic lipase Pancreatic lipases () are a protein family, family of lipolytic enzymes that hydrolyse ester linkages of triglycerides. Lipases are widely distributed in animals, plants and prokaryotes. At least three tissue-specific isozymes exist in higher ...
cleaves triglyceride molecules into two fatty acids and one 2-monoacylglycerol.
Enterocyte Enterocytes, or intestinal absorptive cells, are simple columnar epithelial cells which line the inner surface of the small and large intestines. A glycocalyx surface coat contains digestive enzymes. Microvilli on the apical surface increase ...
s readily absorb the small molecules from the chymus. Inside of the enterocytes, fatty acids and monoacylglycerides are transformed again into triglycerides. Then these lipids are assembled with
apolipoprotein B-48 Apolipoprotein B (ApoB) is a protein that in humans is encoded by the gene. Its measurement is commonly used to detect the risk of atherosclerotic cardiovascular disease. Isoforms The protein occurs in the plasma in two main isoforms, Apo ...
into ''nascent
chylomicron Chylomicrons (from the Greek χυλός, chylos, meaning ''juice'' (of plants or animals), and micron, meaning ''small''), also known as ultra low-density lipoproteins (ULDL), are lipoprotein particles that consist of triglycerides (85–92%), ...
s''. These particles are then secreted into the
lacteal A lacteal is a Lymph capillary, lymphatic capillary that absorbs dietary fats in the Intestinal villus, villi of the small intestine. Triglycerides are emulsified by bile and hydrolyzed by the enzyme lipase, resulting in a mixture of fatty acids, ...
s in a process that depends heavily on apolipoprotein B-48. As they circulate through the
lymphatic vessels The lymphatic vessels (or lymph vessels or lymphatics) are thin-walled vessels (tubes), structured like blood vessels, that carry lymph. As part of the lymphatic system, lymph vessels are complementary to the cardiovascular system. Lymph vessel ...
, nascent chylomicrons bypass the liver circulation and are drained via the
thoracic duct In human anatomy, the thoracic duct (also known as the ''left lymphatic duct'', ''alimentary duct'', ''chyliferous duct'', and ''Van Hoorne's canal'') is the larger of the two lymph ducts of the lymphatic system (the other being the right lymph ...
into the bloodstream. In the blood stream, ''nascent chylomicron particles'' interact with HDL particles, resulting in HDL donation of
apolipoprotein C-II Apolipoprotein C-II (Apo-CII, or Apoc-II), or apolipoprotein C2 is a protein that in humans is encoded by the gene. The protein encoded by this gene is secreted in plasma, where it is a component of very low density lipoproteins and chylomic ...
and
apolipoprotein E Apolipoprotein E (Apo-E) is a protein involved in the metabolism of fats in the body of mammals. A subtype is implicated in Alzheimer's disease and cardiovascular diseases. It is encoded in humans by the gene ''APOE''. Apo-E belongs to a family ...
to the nascent chylomicron. The chylomicron at this stage is then considered mature. Via apolipoprotein C-II, mature chylomicrons activate
lipoprotein lipase Lipoprotein lipase (LPL) (EC 3.1.1.34, systematic name triacylglycerol acylhydrolase (lipoprotein-dependent)) is a member of the lipase gene family, which includes pancreatic lipase, hepatic lipase, and endothelial lipase. It is a water-solubl ...
(LPL), an enzyme on
endothelial cell The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and th ...
s lining the blood vessels. LPL catalyzes the
hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...
of triglycerides that ultimately releases glycerol and
fatty acid In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated and unsaturated compounds#Organic chemistry, saturated or unsaturated. Most naturally occurring fatty acids have an ...
s from the chylomicrons. Glycerol and fatty acids can then be absorbed in peripheral tissues, especially
adipose Adipose tissue (also known as body fat or simply fat) is a loose connective tissue composed mostly of adipocytes. It also contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, Blood vessel, vascular endothel ...
and
muscle Muscle is a soft tissue, one of the four basic types of animal tissue. There are three types of muscle tissue in vertebrates: skeletal muscle, cardiac muscle, and smooth muscle. Muscle tissue gives skeletal muscles the ability to muscle contra ...
, for energy and storage. The hydrolyzed chylomicrons are now called ''chylomicron remnants''. The chylomicron remnants continue circulating the bloodstream until they interact via apolipoprotein E with chylomicron remnant receptors, found chiefly in the liver. This interaction causes the
endocytosis Endocytosis is a cellular process in which Chemical substance, substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a Vesicle (biology and chem ...
of the chylomicron remnants, which are subsequently hydrolyzed within
lysosome A lysosome () is a membrane-bound organelle that is found in all mammalian cells, with the exception of red blood cells (erythrocytes). There are normally hundreds of lysosomes in the cytosol, where they function as the cell’s degradation cent ...
s. Lysosomal
hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...
releases glycerol and fatty acids into the cell, which can be used for energy or stored for later use.


Endogenous pathway

The liver is the central platform for the handling of lipids: it is able to store glycerols and fats in its cells, the
hepatocytes A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, bile ...
. Hepatocytes are also able to create triglycerides via de novo synthesis. They also produce the bile from cholesterol. The intestines are responsible for absorbing cholesterol. They transfer it over into the blood stream. In the hepatocytes, triglycerides and cholesteryl esters are assembled with apolipoprotein B-100 to form ''nascent VLDL particles''. Nascent VLDL particles are released into the bloodstream via a process that depends upon apolipoprotein B-100. In the blood stream, ''nascent VLDL particles'' bump with HDL particles; as a result, HDL particles donate
apolipoprotein C-II Apolipoprotein C-II (Apo-CII, or Apoc-II), or apolipoprotein C2 is a protein that in humans is encoded by the gene. The protein encoded by this gene is secreted in plasma, where it is a component of very low density lipoproteins and chylomic ...
and apolipoprotein E to the nascent VLDL particle. Once loaded with apolipoproteins C-II and E, the nascent VLDL particle is considered mature. VLDL particles circulate and encounter LPL expressed on
endothelial cell The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and th ...
s. Apolipoprotein C-II activates LPL, causing hydrolysis of the VLDL particle and the release of glycerol and fatty acids. These products can be absorbed from the blood by peripheral tissues, principally adipose and muscle. The hydrolyzed VLDL particles are now called VLDL remnants or
intermediate-density lipoprotein Intermediate-density lipoproteins (IDLs) belong to the lipoprotein particle family and are formed from the degradation of very low-density lipoproteins as well as high-density lipoproteins. IDL is one of the five major groups of lipoproteins (chylo ...
s (IDLs). VLDL remnants can circulate and, via an interaction between apolipoprotein E and the remnant receptor, be absorbed by the liver, or they can be further hydrolyzed by
hepatic lipase Hepatic lipase (HL), also called hepatic triglyceride lipase (HTGL) or LIPC (for "lipase, hepatic"), is a form of lipase, catalyzing the hydrolysis of triacylglyceride. Hepatic lipase is coded by chromosome 15 and its gene is also often referre ...
. Hydrolysis by hepatic lipase releases glycerol and fatty acids, leaving behind ''IDL remnants'', called
low-density lipoprotein Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall density ...
s (LDL), which contain a relatively high cholesterol content (). LDL circulates and is absorbed by the liver and peripheral cells. Binding of LDL to its target tissue occurs through an interaction between the
LDL receptor The low-density lipoprotein receptor (LDL-R) is a mosaic protein of 839 amino acids (after removal of 21-amino acid signal peptide) that mediates the endocytosis of cholesterol-rich low-density lipoprotein (LDL). It is a cell-surface receptor ...
and apolipoprotein B-100 on the LDL particle. Absorption occurs through
endocytosis Endocytosis is a cellular process in which Chemical substance, substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a Vesicle (biology and chem ...
, and the internalized LDL particles are hydrolyzed within lysosomes, releasing lipids, chiefly cholesterol.


Possible role in oxygen transport

Plasma lipoproteins may carry oxygen gas. This property is due to the crystalline hydrophobic structure of lipids, providing a suitable environment for O2 solubility compared to an aqueous medium.


Role in inflammation

Inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
, a biological system response to stimuli such as the introduction of a
pathogen In biology, a pathogen (, "suffering", "passion" and , "producer of"), in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a Germ theory of d ...
, has an underlying role in numerous systemic biological functions and pathologies. This is a useful response by the immune system when the body is exposed to pathogens, such as bacteria in locations that will prove harmful, but can also have detrimental effects if left unregulated. It has been demonstrated that lipoproteins, specifically HDL, have important roles in the inflammatory process. When the body is functioning under normal, stable physiological conditions, HDL has been shown to be beneficial in several ways. LDL contains apolipoprotein B (apoB), which allows LDL to bind to different tissues, such as the artery wall if the
glycocalyx The glycocalyx (: glycocalyces or glycocalyxes), also known as the pericellular matrix and cell coat, is a layer of glycoproteins and glycolipids which surround the cell membranes of bacteria, epithelial cells, and other cells. Animal epithe ...
has been damaged by high
blood sugar level The blood sugar level, blood sugar concentration, blood glucose level, or glycemia is the measure of glucose concentrated in the blood. The body tightly regulates blood glucose levels as a part of metabolic homeostasis. For a 70 kg (1 ...
s. If oxidised, the LDL can become trapped in the proteoglycans, preventing its removal by HDL cholesterol efflux. Normal functioning HDL is able to prevent the process of oxidation of LDL and the subsequent inflammatory processes seen after oxidation.
Lipopolysaccharide Lipopolysaccharide (LPS), now more commonly known as endotoxin, is a collective term for components of the outermost membrane of the cell envelope of gram-negative bacteria, such as '' E. coli'' and ''Salmonella'' with a common structural archit ...
, or LPS, is the major pathogenic factor on the cell wall of
Gram-negative bacteria Gram-negative bacteria are bacteria that, unlike gram-positive bacteria, do not retain the Crystal violet, crystal violet stain used in the Gram staining method of bacterial differentiation. Their defining characteristic is that their cell envelo ...
.
Gram-positive bacteria In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. The Gram stain ...
has a similar component named
Lipoteichoic acid Lipoteichoic acid (LTA) is a major constituent of the cell wall of gram-positive bacteria. These organisms have an inner (or cytoplasmic) membrane and, external to it, a thick (up to 80 nanometer) peptidoglycan layer. The structure of LTA varies b ...
, or LTA. HDL has the ability to bind LPS and LTA, creating HDL-LPS complexes to neutralize the harmful effects in the body and clear the LPS from the body. HDL also has significant roles interacting with cells of the immune system to modulate the availability of cholesterol and modulate the immune response. Under certain abnormal physiological conditions such as system
infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...
or
sepsis Sepsis is a potentially life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage of sepsis is followed by suppression of the immune system. Common signs and s ...
, the major components of HDL become altered, The composition and quantity of lipids and apolipoproteins are altered as compared to normal physiological conditions, such as a decrease in HDL cholesterol (HDL-C), phospholipids, apoA-I (a major lipoprotein in HDL that has been shown to have beneficial anti-inflammatory properties), and an increase in Serum amyloid A. This altered composition of HDL is commonly referred to as acute-phase HDL in an acute-phase inflammatory response, during which time HDL can lose its ability to inhibit the oxidation of LDL. In fact, this altered composition of HDL is associated with increased mortality and worse clinical outcomes in patients with sepsis.


Classification


By density

Lipoproteins may be classified as five major groups, listed from larger and lower density to smaller and higher density. Lipoproteins are larger and less dense when the fat to protein ratio is increased. They are classified on the basis of
electrophoresis Electrophoresis is the motion of charged dispersed particles or dissolved charged molecules relative to a fluid under the influence of a spatially uniform electric field. As a rule, these are zwitterions with a positive or negative net ch ...
, ultracentrifugation and
nuclear magnetic resonance spectroscopy Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a Spectroscopy, spectroscopic technique based on re-orientation of Atomic nucleus, atomic nuclei with non-zero nuclear sp ...
via th
Vantera Analyzer
*
Chylomicron Chylomicrons (from the Greek χυλός, chylos, meaning ''juice'' (of plants or animals), and micron, meaning ''small''), also known as ultra low-density lipoproteins (ULDL), are lipoprotein particles that consist of triglycerides (85–92%), ...
s carry triglycerides (fat) from the intestines to the liver, to
skeletal muscle Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...
, and to adipose tissue. *
Very-low-density lipoprotein Very-low-density lipoprotein (VLDL), density relative to extracellular water, is a type of lipoprotein made by the liver. VLDL is one of the five major groups of lipoproteins (chylomicrons, VLDL, intermediate-density lipoprotein, low-density lip ...
s (VLDL) carry (newly synthesised) triglycerides from the liver to adipose tissue. *
Intermediate-density lipoprotein Intermediate-density lipoproteins (IDLs) belong to the lipoprotein particle family and are formed from the degradation of very low-density lipoproteins as well as high-density lipoproteins. IDL is one of the five major groups of lipoproteins (chylo ...
s (IDL) are intermediate between VLDL and LDL. They are not usually detectable in the blood when
fasting Fasting is the act of refraining from eating, and sometimes drinking. However, from a purely physiological context, "fasting" may refer to the metabolic status of a person who has not eaten overnight (before "breakfast"), or to the metabolic sta ...
. *
Low-density lipoprotein Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall density ...
s (LDL) carry 3,000 to 6,000 fat molecules (phospholipids, cholesterol, triglycerides, etc.) around the body. LDL particles are sometimes referred to as "bad" lipoprotein because concentrations of two kinds of LDL (sd-LDL and LPA), correlate with atherosclerosis progression. In healthy individuals, most LDL is large and buoyant (lb LDL). ** large buoyant LDL (lb LDL) particles ** small dense LDL (sd LDL) particles ** Lipoprotein(a) (LPA) is a lipoprotein particle of a certain phenotype *
High-density lipoprotein High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are t ...
s (HDL) collect fat molecules from the body's cells/tissues and take them back to the liver. HDLs are sometimes referred to as "good" lipoprotein because higher concentrations correlate with low rates of atherosclerosis progression and/or regression. For young healthy research subjects, ~70 kg (154 lb), these data represent averages across individuals studied, percentages represent % dry weight: However, these data are not necessarily reliable for any one individual or for the general clinical population.


Alpha and beta

It is also possible to classify lipoproteins as "alpha" and "beta", according to the classification of proteins in
serum protein electrophoresis Serum protein electrophoresis (SPEP or SPE) is a laboratory test that examines specific proteins in the blood called globulins. The most common indications for a serum protein electrophoresis test are to diagnose or monitor multiple myeloma, a ...
. This terminology is sometimes used in describing lipid disorders such as
abetalipoproteinemia Abetalipoproteinemia (also known as: Bassen–Kornzweig syndrome, microsomal triglyceride transfer protein deficiency disease, MTP deficiency, and betalipoprotein deficiency syndrome) is a disorder characterized by abnormal absorption of fat and ...
.


Subdivisions

Lipoproteins, such as LDL and HDL, can be further subdivided into subspecies isolated through a variety of methods. These are subdivided by density or by the protein contents/ proteins they carry. While the research is currently ongoing, researchers are learning that different subspecies contain different apolipoproteins, proteins, and lipid contents between species which have different physiological roles. For example, within the HDL lipoprotein subspecies, a large number of proteins are involved in general lipid metabolism. However, it is being elucidated that HDL subspecies also contain proteins involved in the following functions:
homeostasis In biology, homeostasis (British English, British also homoeostasis; ) is the state of steady internal physics, physical and chemistry, chemical conditions maintained by organism, living systems. This is the condition of optimal functioning fo ...
,
fibrinogen Fibrinogen (coagulation factor I) is a glycoprotein protein complex, complex, produced in the liver, that circulates in the blood of all vertebrates. During tissue and vascular injury, it is converted Enzyme, enzymatically by thrombin to fibrin ...
, clotting cascade, inflammatory and immune responses, including the
complement system The complement system, also known as complement cascade, is a part of the humoral, innate immune system and enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inf ...
,
proteolysis Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Protein degradation is a major regulatory mechanism of gene expression and contributes substantially to shaping mammalian proteomes. Uncatalysed, the hydrolysis o ...
inhibitors, acute-phase response proteins, and the LPS-binding protein,
heme Heme (American English), or haem (Commonwealth English, both pronounced /Help:IPA/English, hi:m/ ), is a ring-shaped iron-containing molecule that commonly serves as a Ligand (biochemistry), ligand of various proteins, more notably as a Prostheti ...
and iron metabolism,
platelet Platelets or thrombocytes () are a part of blood whose function (along with the coagulation#Coagulation factors, coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a thrombus, blood clot. Platelets have no ...
regulation, vitamin binding and general transport.


Research

High levels of lipoprotein(a) are a significant
risk factor In epidemiology, a risk factor or determinant is a variable associated with an increased risk of disease or infection. Due to a lack of harmonization across disciplines, determinant, in its more widely accepted scientific meaning, is often use ...
for
atherosclerotic Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. This is a chronic inflammatory disease involving many different cell types and is driven by elev ...
cardiovascular disease Cardiovascular disease (CVD) is any disease involving the heart or blood vessels. CVDs constitute a class of diseases that includes: coronary artery diseases (e.g. angina, heart attack), heart failure, hypertensive heart disease, rheumati ...
s via mechanisms associated with
inflammation Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', '' ...
and
thrombosis Thrombosis () is the formation of a Thrombus, blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel (a vein or an artery) is injured, the body uses platelets (thrombocytes) and fib ...
. The links of mechanisms between different lipoprotein isoforms and risk for cardiovascular diseases, lipoprotein synthesis, regulation, and metabolism, and related risks for
genetic disease A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosome abnormality. Although polygenic disorders are ...
s are under active research, as of 2022.


See also

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Lipid anchored protein Lipids are a broad group of organic compounds which include fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include storing ene ...
*
Remnant cholesterol Remnant cholesterol, also known as remnant lipoprotein and triglyceride-rich lipoprotein cholesterol is an atherogenic lipoprotein composed primarily of very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) with chylomicr ...
*
Reverse cholesterol transport Reverse cholesterol transport (RCT) is a multistep process comprising removal of excess cholesterol from cells in the body and delivery to the liver for excretion into the small intestine. Enhancing reverse cholesterol transport is considered a po ...
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References


External links

* {{Authority control Lipids * Physiology Cardiology he:כולסטרול#ליפופרוטאינים