Receptor-dependent and -independent catabolism of low-density lipoprotein in a kindred with familial hypobetalipoproteinemia.
Three affected members of a kindred with asymptomatic hypobetalipoproteinemia (HBL) were injected intravenously with 125I-labeled native low-density lipoproteins (LDL) and 131I-labeled cyclohexanedione (CHD)-treated LDL. Plasma and urine radioactivity data were collected for 15 days at regular intervals. A compartmental model using the SAAM program was built to fit simultaneously 125I and 131I plasma radioactivity decay and urine excretion data. This model allows precise calculation of the kinetic parameters of both receptor-independent (NR) and receptor-dependent (R) pathways. Compared with normal subjects, HBL patients show a 90% increased fractional catabolic rate (FCR) of LDL by both routes, more marked for the R pathway (215% increase), and an approximately 50% reduced production rate (PR). Structural analysis did not show significant abnormalities of apolipoprotein (apo) B in HBL patients compared with normal. These data suggest that the very reduced, LDL-apo B plasma levels result from a combination of two processes: (1) an increased activity of all catabolic routes, and (2) a reduced "synthesis" rate. The latter may result from a decreased conversion of very-low-density lipoprotein (VLDL) to LDL secondary to an increased direct removal of large VLDL, suggested by apo C-II and C-III turnover studies previously reported.
Malmendier
C L
CL
Research Foundation on Atherosclerosis, Brussels, Belgium.
Lontie
J F
JF
Delcroix
C
C
Sérougne
C
C
Férézou
J
J
Lee
D M
DM
D000293:Adolescent; D000328:Adult; D001055:Apolipoproteins B / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D006995:Hypobetalipoproteinemias / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011973:Receptors, LDL / Q000502:physiology*
D001055:Apolipoproteins B; D008055:Lipids; D008074:Lipoproteins; D008077:Lipoproteins, LDL; D011973:Receptors, LDL