Carbamylation-induced alterations in low-density lipoprotein metabolism.
Low-density lipoprotein was derived from carbamyl (carbamyl-LDL) by incubating LDL in potassium cyanate (KCNO). The proportion of free amino groups in the carbamyl-LDL was negatively correlated (r = -0.95) with the time of incubation in potassium cyanate (ranged from 5 to 360 min). The carbamylation did not change the chemical composition or the flotation characteristics of the LDL particles. However, the electrophoretic mobility of carbamyl-LDL was distinctly increased with the extent of carbamylation. The carbamyl-LDL had substantially decreased binding to the LDL apoB/E receptors of the bovine adrenocortical membranes when compared to the control-LDL. The reduced binding was already observed when only 9% of the free amino groups were derived from carbamyl. A minor carbamylation of LDL (less than 20% of the free amino groups) decreased the in vivo clearance of LDL from rabbit plasma. However, when more than 20% of the free amino groups were derived the carbamyl-LDL had accelerated clearance compared to the control-LDL. LDL isolated from uremic patients was cleared in rabbits at a slower rate than LDL isolated from a control subject. Providing that carbamylation of LDL could also occur in vivo resulting in similar alterations of the LDL binding to the LDL B/E receptors, as observed in the present study, the uremia-related accelerated atherosclerosis could have one additional mechanistic explanation.
Hörkkö
S
S
Department of Internal Medicine, University of Oulu, Finland.
Savolainen
M J
MJ
Kervinen
K
K
Kesäniemi
Y A
YA
D000302:Adrenal Cortex / Q000378:metabolism; D000818:Animals; D002417:Cattle; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D018110:Receptors, Lipoprotein
D008077:Lipoproteins, LDL; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; C032531:apolipoprotein B,E receptor; C039916:carbamyl-LDL