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J. Biol. Chem., Vol. 261, Issue 19, 8712-8718, Jul, 1986
GM Fless, ME ZumMallen and AM Scanu
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.
Physicochemical properties of apolipoprotein(a) and lipoprotein(a-) derived from the dissociation of human plasma lipoprotein (a)
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