| Apolipoprotein | |||||||
|---|---|---|---|---|---|---|---|
 Apolipoprotein e3 (Apoe3) | |||||||
| Identifiers | |||||||
| Symbol | Apolipoprotein | ||||||
| Pfam | PF01442 | ||||||
| InterPro | IPR000074 | ||||||
| SCOP2 | 1oef /SCOPe /SUPFAM | ||||||
| OPM superfamily | 172 | ||||||
| OPM protein | 3r2p | ||||||
| |||||||
Apolipoproteins areproteins that bindlipids (oil-soluble substances such as fats,cholesterol andfat soluble vitamins) to formlipoproteins. They transport lipids inblood,cerebrospinal fluid andlymph.
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 a lipoprotein particle that is itself water-soluble, and can thus be carried throughbody fluids (i.e., blood, lymph).
In addition to stabilizing lipoprotein structure and solubilizing the lipid component, apolipoproteins interact with lipoprotein receptors and lipid transport proteins, thereby participating in lipoprotein uptake and clearance. They also serve asenzymecofactors for specificenzymes involved in the metabolism of lipoproteins.[1]
Apolipoproteins are also exploited byhepatitis C virus (HCV) to enable virus entry, assembly, and transmission. They play a role in viral pathogenesis and viral evasion from neutralizing antibodies.[2]
Different lipoproteins contain different classes of apolipoproteins, which influence their function.
Apolipoprotein A-I (apoA1) is the major structural protein component ofhigh-density lipoproteins (HDL), although it is present in other lipoproteins in smaller amounts.[3]Apolipoprotein A-IV (apoA4) is present inchylomicrons,very-low-density lipoproteins (VLDL), and HDL. It is thought to act primarily inreverse cholesterol transport[4] andintestinal lipid absorption via chylomicron assembly and secretion. ApoA-IV synthesized in hypothalamus is suggested to be a satiating factor which regulates the food intake of the rodent.[5][1]
Apolipoprotein B plays a particularly important role in lipoprotein transport being the primary organizing protein of many lipoproteins.[1]
Apolipoprotein C-III (apoC3) plays an important role in lipid metabolism specific in regulating the metabolism of triglyceride-rich lipoproteins (TRLs).[6]
Apolipoprotein D (apoD) is a soluble carrier protein of lipophilic molecules in neurons and glial cells within the central and peripheral nervous system and apoD can also modulate the stability and oxidation status of these molecules.[7]
Apolipoprotein E (apoE) plays an important role in the transport and uptake ofcholesterol by way of its high affinity interaction with lipoprotein receptors, including thelow-density lipoprotein (LDL)receptor. ApoE is the major lipoprotein in thecentral nervous system. Recent findings with apoA1 and apoE suggest that thetertiary structures of these two members of thehuman exchangeable apolipoproteingene family are related.[8] The three-dimensionalstructure of the LDL receptor-bindingdomain of apoE indicates that the protein forms an unusually elongated four-helix bundle that may be stabilised by a tightly packedhydrophobic core that includesleucine zipper-type interactions and by numeroussalt bridges on the mostly charged surface.Basicamino acids important for LDLreceptorbinding are clustered into a surface patch on one longhelix.[9]
Apolipoprotein F (apoF) is one of the minor apolipoprotein in blood plasma and it is a lipid transfer inhibit protein to inhibit cholesteryl ester transfer protein-mediated transfers of cholesteryl esters and triglycerides.[10][11]
Apolipoprotein M (apoM) participates in the lipid metabolism and exhibit anti‑atherosclerotic functions and it is presented in high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL).[12]
There are multiple classes of apolipoproteins and several sub-classes:
Exchangeable apolipoproteins (apoA, apoC, and apoE) have the samegenomic structure and are members of a multi-gene family that probablyevolved from a common ancestralgene. Apo-AI and ApoA4 are part of the APOA1/C3/A4/A5gene cluster onchromosome 11.[14]
Hundreds of geneticpolymorphisms of the apolipoproteins have been described, and many of them alter their structure and function.
The cluster of exchangeable apoliproteins is well conserved invertebrates.[15] The family diversified by duplication, with the ancestral gene most similar to ApoC1.[16]
Beyond vertebrates, proteins similar to the exchangeable ApoA/C/E and the nonexchangable Apo-B are found in a wide range of animals andchoanoflagellates. This suggests that the ancestral animal already has both kinds of apolipoproteins. Inarthropods in particular,diacylglycerol-carrying apolipoproteins are known asapolipophorins, with the ApoA/C/E-like one known asapolipophorin III and the Apo-B like one known asapolipophorin I/II.[16]
Apolipoprotein synthesis in the intestine is regulated principally by the fat content of the diet.
Apolipoprotein synthesis in the liver is controlled by a host of factors, including dietary composition,hormones (insulin,glucagon,thyroxin,estrogens,androgens),alcohol intake, and various drugs (statins,niacin, andfibric acids). ApoB is an integral apoprotein whereas the others are peripheral apoproteins.
Apolipoprotein synthesis such as ApoA4 in hypothalamus involves in the integration of signals for regulation of food intake[5] which is regulated by vagal nerve andcholecystokinin.[17]
Apolipoprotein has been suggested to be implicated in several types of diseases and dysfunction.
ApoC1 level increases in neuropathic pain and fibromyalgia patients which suggest it plays an important role in occurrence of these conditions.[18]
ApoC3 is a risk factor of cardiovascular disease. Accumulation of plasma TRLs caused by elevated apoC-III leading to hypertriglyceridaemia.[19]
ApoD level increases in nervous system with a large number of neurologic disorders inclusive of Alzheimer's disease, schizophrenia, and stroke.[7]
ApoE has been implicated indementia andAlzheimer's disease.[20]
Apo(a) is a component oflipoprotein(a) (Lp(a)) and elevated plasma Lp(a) level is a heritable, independent, and possibly causal risk factor for Atherosclerotic Cardiovascular Disease (ASCVD).[21] The cholesterol-rich apoB-containing lipoproteins also participate in the pathogenesis of ASCVD.
Lipids:lipoprotein particle metabolism | ||
|---|---|---|
| Lipoprotein particle classes and subclasses |
|  |
| Apolipoproteins | ||
| Extracellularenzymes | ||
| Lipid transfer proteins | ||
| Cell surface receptors | ||
| ATP-binding cassette transporter | ||