Lipoprotein A Essay

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Introduction Lipoprotein A was first discovered in humans by Kare Berg in 1963 whilst a study of variation in LDL antigenicity. The Human gene encoding lipoprotein(a) was cloned in the year 1987(1). Lipoprotein A Structure Lipoprotein A has a similar structure to the LDL molecule with the addition of a covalently bound specific apolipoprotein A (2). Apolipoprotein(A) is a homologue of plasminogen and contains several copies of KRINGLE 4 plasminogen, a single copy of KRINGLE 5 plasminogen and an inactive protease domain (2). Studies have indicated that the number of KRINGLE 4 domains can range from 51 to 12 giving rise to approximately 34 different apo(a) isoforms. Also,10 distinct types of KIV domains exist for the repeated KIV domains, …show more content…

Experiments showing that lysine analogues break down lipoprotein A assembly suggest that lysine binding domains in apo(a) and lysine residues in apo are involved in the primary non-covalent interaction.15. Mutagenesis studies show defective Lp(a) assembly after the removal of lysine binding sites in apo(a) KIV types 6–8 providing further evidence. A recent study of single point mutations introduced into the lysine binding sites in KIV 6–8 has shown that KIV 7 and 8 are essential for efficient lipoprotein A assembly (7). Multiple apoB sequences that noncovalently bind apo(a) are documented. An apoB lysine residue in the N-terminus, apoBLys680 mediating noncovalent binding of an apoB18 fragment to apo(a) have been postulated. Further evidence has shown that a peptide containing the apoBLys680 residue is bound to apo(a) KIV type 7. C-terminal moiety of apoB has also been hypothesized in the noncovalent interaction with apo(a). Truncated apoB molecules found in a region between apoB95 (4330 amino acids) and apoB97 (4397 amino acids) has been said to be important for efficient Lp(a) assembly. Characterisation of the apoB4330 to 4397 regions found a 21-amino acid sequence (amino acids 4372–4392) containing four lysine residues (including a highly conserved lysine at position 4372) that could be an a apo(a) binding site. A peptide spanning this

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