Apolipoproteins

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When apolipoproteins ( apo of Greek άπό : Waste, displacement) refers to the protein fraction of lipoproteins (including chylomicrons , VLDL , LDL , IDL , HDL ), of the water-insoluble lipids transported in the blood. The apolipoproteins, together with phospholipids, form the water-soluble ( hydrophilic ) surface of the lipoproteins, where they act as a structural framework and / or recognition and docking molecule z. B. act for membrane receptors .

Structure, function

Since the apolipoproteins, with the exception of the ApoBs, can switch back and forth between individual lipoprotein particles, the combination of the different apolipoproteins on a lipoprotein changes as the metabolism progresses in the bloodstream. The apolipoprotein composition shows the current lipid composition of the lipoprotein and directs it to the next phase of its metabolic pathway until it is finally absorbed into a body cell , in most cases a liver cell .

Apolipoproteins are produced in the tissues that synthesize lipoproteins, ie in particular in the liver and small intestine . The names of the apolipoproteins are historical (ApoAs were first found in HDL, ApoBs in LDL and their precursors, and ApoCs in VLDL) and are usually composed of a capital letter and, if necessary, a number after it. The following table contains information on some important of the known apolipoproteins.

Apolipoprotein Molecular mass ( kDa ) Occurrence Main place of synthesis function
ApoA-I 29 HDL, chylomicrons Liver, intestines Activator of the LCAT
ApoA-II 17.4 Chylomicrons, HDL Intestines Structural element, activator of hepatic lipase
ApoA-IV 39 Chylomicrons, HDL liver Activator of the LCAT
Apo (a) 300 to 800
(genetic) 		Lp (a) liver unknown, risk factor for CHD
ApoB-48 (not interchangeable) 260 Chylomicrons, remnants Intestines Chylomicron (-remnant) structure
ApoB-100 (not interchangeable) 550 VLDL, IDL, LDL liver Ligand for cellular uptake (ApoB-100 receptor) ( endocytosis via LDL receptor )
ApoC-I 7th HDL, chylomicrons, VLDL liver Activator of the LCAT
ApoC-II 9 Chylomicrons, remnants, VLDL, HDL liver Lipoprotein lipase activator
ApoC-III 9 Chylomicrons, remnants, VLDL, HDL liver Lipoprotein lipase inhibitor
ApoD 33 HDL liver Activator of the LCAT, structural element
ApoE 35 Chylomicrons, remnants, VLDL, IDL, HDL Liver, macrophages Ligand for cellular uptake ( endocytosis via ApoE receptor)

The ApoA and ApoC proteins as well as ApoE are structurally similar, since they contain many, repeating, amphipathic α-helices , which at the genetic level consist of tandem repeats of 11 codons and therefore very likely evolved from an original gene. Interestingly, these genes are distributed over two gene clusters in the human genome : ApoC-I / -II / -IV / ApoE on chromosome 19q3.2-q3.3 and ApoA-I / -IV / -V / ApoC-III on chromosome 11q23-q24. In contrast, the two ApoB proteins are transcribed by a single gene (ApoB-48 is produced by RNA editing - in humans only in the small intestinal epithelium ) and consist predominantly of extensive amphipathic β-sheet structures, which are presumably responsible for the strong association with the Lipid core are responsible.

A number of disorders of lipid metabolism can be traced back to defects in the production of apolipoproteins or their docking points on the cell wall (e.g. the LDL receptor ). The measurement of the blood levels of the various apolipoproteins is part of the diagnosis of these diseases, the clinical relevance of which is particularly high because a disturbed lipid metabolism usually affects the risk of arteriosclerosis and thus the life expectancy of the patient.

ApoA-I (M), a genetic variant of ApoA-I, the so-called Milano type, is currently being investigated to see whether it is suitable as a therapeutic agent for atherosclerosis , as the carriers of this trait, the Milanese fat researcher Cesare Sirtori in town Limone sul Garda on Lake Garda, are characterized by long life and low levels of atherosclerosis. Contrary to the usual fact that a high HDL is a protective factor against arteriosclerosis, the carriers of the ApoA-I (M) have low HDL values. ApoA-I (M) is able to dimerize through an amino acid exchange , thus has a longer plasma half-life, can mobilize cholesterol more efficiently and presumably leads in this way to a reduction in atherosclerotic plaques .

literature

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