Apolipoproteins are proteins that coat lipoprotein surface that binds lipids such as cholesterol, low-density lipoprotein (LDL), or high-density lipoproteins (HDL) in lipid metabolism. They function in the transport of such lipids in their structure that acts as a ligand to cell receptors and lipid transport proteins. ^[1] They are important in the binding and transportation of lipids throughout the body, necessary in energy structural components, and nutrients.

Apolipoprotein A-I is a protein of APOA1 gene located on the 11th chromosome found in humans that is a component of HDL. Gene for APOA1 protein contains a total of 4 exons that is synthesized for the protein, used in lipid metabolism of HDL. ^[2] Apolipoprotein a-1 (apoA-I) is a fairly small molecule that consists of a total of 243 residues and is 29-kD polypeptide in size. Structure in is shown in rainbow, in arrangement from N-terminus (red) of amine group to C-terminus (dark blue) end of carboxyl group.

Function

Apolipoprotein A-I contains amphipathic structure sequences of helices in its repeating hydrophilic and non-polar hydrophobic groups that form helices are what allows the interaction between hydrophobic properties of water, such as in the blood stream and hydrophobic lipids.

Apolipoprotein A-I is a protein APOA1 gene in humans that is a component of HDL, which a form of good cholesterol in human's diet, used in the transport of cholesterol and phospholipids in the body through the bloodstream in the reverse transport of cholesterol from the tissues to the liver of hepatocytes. They promote cholesterol efflux, a pathway in transferring intracellular cholesterol to extracellular acceptors, from tissues and act as a cofactor for the lecithin cholesterol acyltransferase (LCAT).^[3]

Clinical significance

Apolipoprotein A-1 is found to be as an indicator for cardiovascular disease and atherosclerotic cardiovascular disease. Since APOA1 is a component of HDL associated with good form of cholesterol, when ABOAB (apolipoprotein B) a component of LDL, a form of bad cholesterol levels are elevated in blood can signal as a risk factor for development in hardening of arterial walls and blockage. ^[4] High-density lipoprotein complex is important in the clearing of fats through absorption of cholesterol that is transported into the liver where it is synthesized into bile salts or excreted.^[5][6]

Apolipoprotein A-I (Milano) is a mutant form of apolipoprotein A-I associated in reducing coronary artery disease to those genetically predisposition. ^[7] Mutation Milano was first discovered in from a patient in Limone sul Garda, Northern Italy or alarming elevated triglycerides and low HDL with no signs of atherosclerosis or cardiovascular disease. Mutation occurs at 173 residue of replaced with cysteine. ^[8]

Diseases

Tangier disease

Genetic disorder with significantly reduced HDL in the blood caused by mutation of APOA1 gene (ABCA1) caused by abnormal pre-mRNA spicing, in the loss of 22 amino acids of premature stop codon.^[9] As a result of decreased apolipoprotein A-1 synthesized, cells undergo large lipid fluxes and accumulated cholesterol and fats. Accumulation of cholesterol in cell due to lack of transport is toxic and impairs cell function. Visible signs of the disease include yellow-orange tonsils and formation of foam cells of lipid-laden macrophages.^[10]

Alzheimer’s

Structural highlights

Apolipoprotein a-1 (apoA-I) is a fairly small molecule that consists of a total of 243 residues and is 29-kD polypeptide in size. Its structure consists of two helical domains that include a four-helix of antiparallel bundle by N terminal and two helix bundle at the C terminal end. ApoA-I consists of alpha helices including chain A (orange), B (blue), C (red), and D (green) as displayed, in which an infinity like structure. C terminal domain of carboxyl group is known to participate in role in lipid binding for transport, found following between residues At the central region, two antiparallel helices form a flexible domain of connected bundles of each end of helices.^[11]

Apolipoprotein a-1 in the monomer form (lacking 1-43 residues) consists of unique pseudo-continuous alpha helix highlighted by kinks at , spaced approximately every 22 residues.^[12]

Biomarkers of coronary artery disease are also found to be of modification at glutamate residue 243 of truncated APOA1 of single amino acid.