Physicochemical properties of apolipoprotein(a) and lipoprotein(a-) derived from the dissociation of human plasma lipoprotein (a).
Chemical reduction of human plasma lipoprotein(a) (Lp(a)) yielded two water-soluble products which were separated by rate zonal ultracentrifugation. Apolipoprotein(a) (apo(a)) was completely recovered from the bottom of the gradient, whereas lipoprotein(a-) (Lp(a-)), which contained all of the lipids and apo-B100 of Lp(a), floated. By the techniques of circular dichroism and viscometry Lp(a-) was identical to low density lipoprotein (LDL). Lp(a-) was slightly larger in mass than autologous LDL and contained proportionally more triglyceride. The difference in mass between Lp(a) and Lp(a-) was accounted for by the loss of 2 molecules of apo(a) from the Lp(a) particle. The molecular weight of reduced and carboxymethylated apo(a) was 281,000 as determined by sedimentation equilibrium in 6 M guanidine HCl. By circular dichroism the structure of apo(a) was mostly random (71%) with the remainder representing 8% alpha-helix and 21% beta-sheet; its intrinsic viscosity, 28.3 cm3/g, was consistent with an extended flexible coil. The amino acid composition was characterized by an unusually high content of proline (11.4 mol %) as well as tryptophan, tyrosine, arginine, threonine, and a low amount of lysine, phenylalanine, and isoleucine. Apo(a) contained 28.1% carbohydrate by weight represented by mannose, galactose, galactosamine, glucosamine, and sialic acid in an approximate molar ratio of 3:7:5:4:7, respectively. Overall, the structure of Lp(a) appears to be consistent with a rigid spherical LDL-like core particle which, as a consequence of its association with a flexible glycoprotein such as apo(a), favors the entrapment of significant amounts of hydrodynamically associated solvent. Furthermore, the Lp(a-) remnant generated by the removal of apo(a) from Lp(a) was similar in structure but not identical to autologous LDL.
D000328:Adult; D000596:Amino Acids / Q000032:analysis; D001053:Apolipoproteins / Q000097:blood; D001054:Apolipoproteins A / Q000097:blood*; D002241:Carbohydrates / Q000032:analysis; D002501:Centrifugation, Zonal / Q000379:methods; D002784:Cholesterol / Q000032:analysis; D002788:Cholesterol Esters / Q000032:analysis; D002942:Circular Dichroism; D005260:Female; D006801:Humans; D017270:Lipoprotein(a); D008074:Lipoproteins / Q000097:blood*; D008970:Molecular Weight; D010743:Phospholipids / Q000032:analysis; D011487:Protein Conformation; D014280:Triglycerides / Q000032:analysis; D014783:Viscosity
D000596:Amino Acids; D001053:Apolipoproteins; D001054:Apolipoproteins A; D002241:Carbohydrates; D002788:Cholesterol Esters; D017270:Lipoprotein(a); D008074:Lipoproteins; D010743:Phospholipids; D014280:Triglycerides; D002784:Cholesterol