Abstract
In early reports by Kare Berg from Oslo, Norway, Lp(a) was described as a pre-ß1 lipoprotein found in the region of HDL by ultracentrifugation. Subsequent studies from numerous laboratories revealed that Lp(a) consists of an LDL-like core particle and the characteristic apo(a) glycoprotein both linked by one disulfide bridge. Since the lipid composition of LDL varies quite considerably among patients, it is evident that this might be also the case for Lp(a). Most of the structural and compositional studies on Lp(a) were performed on preparations obtained from healthy fasting normolipemic individuals where fractions in the density of HDL1 were harvested. The composition of Lp(a) preparations from non-fasting—dyslipoproteinemic individuals—or from density fractions outside of HDL1 is by far less clear.
Idealized Lp(a) preparations with a hydrated density characteristic for HDL1 consist of a core that is indistinguishable from parent LDL. Their morphology by electron microscopy is very similar to that of LDL. Such Lp(a) is rich in cholesteryl esters and phospholipids and has lower amounts of free cholesterol and triglycerides. The characteristic Lp(a) antigen, apo(a), is a glycoprotein with up to 30% w/w of N- and O-glycosylated sugars, rich in sialic acid. The terminal sialic acid of apo(a) prevents its fast catabolism by specific asialo-glycoprotein receptors on liver cells. The protein backbone of apo(a) has a characteristic structure dominated by so-called kringles that are highly homologous to kringle-IV of plasminogen. There is also a kringle-V like structure and a protease domain found in apo(a) whose gene and protein sequence are very similar to those found in plasminogen.
The various kringles found in apo(a) are not only key for the assembly with LDL to form Lp(a) but also impact profoundly the Lp(a) metabolism. On one side, kringles are responsible for binding to Lys groups on LDL, and on the other side, they mediate binding of apo(a) to cell surfaces followed by catabolism or degradation. There are numerous mutated and polymorphic forms of apo(a) that show altered metabolism. In a similar way, the morphology and composition of LDL greatly impact the assembly and metabolism of Lp(a) as evident from studies with LDL from LCAT-deficient patients or patients with the B-3500 mutation of apoB-100.
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Abbreviations
- Apo(a):
-
Specific antigen of Lp(a)
- ASGPR:
-
Asialo-glycoprotein receptor
- LCAT:
-
Lecithin:cholesterol acyl transferase
- LDL:
-
Low-density lipoprotein
- Lp:
-
Lipoprotein
- Lp(a):
-
Lipoprotein(a)
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Kostner, G.M. (2023). Lp(a) Biochemistry, Composition, and Structure. In: Kostner, K., Kostner, G.M., Toth, P.P. (eds) Lipoprotein(a). Contemporary Cardiology. Humana, Cham. https://doi.org/10.1007/978-3-031-24575-6_2
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