Further insights into the pathophysiology of hyperapobetalipoproteinemia: role of basic proteins I, II, III.
Hyperapobetalipoproteinemia (hyperapoB), a familial lipoprotein disorder characterized by an increase in small, dense, low-density lipoprotein (LDL) particles, is strongly associated with coronary artery disease. There are two metabolic defects in hyperapoB: an increased synthesis of a very-low-density lipoprotein in liver, resulting in an overproduction of LDL, and a delayed clearance of post-prandial triglyceride and free fatty acids. To date, defects in the apolipoprotein B gene do not appear to explain the hyperapoB phenotype. Defect(s) in the uptake or intracellular metabolism of free fatty acids have been found in cells from hyperapoB patients. Three basic proteins (BPs)--BP I (Mr 14,000, pI 9.10), BP II (Mr 27,500, pI 8.48), and BP III (Mr 55,000, pI 8.73)--were isolated from normal human serum. Compared with normal fibroblasts, cultured hyperapoB fibroblasts incubated with BP I, which appears to be the same protein as acylation-stimulating protein (ASP), showed 50% less stimulation of triglyceride acylation and cholesterol esterification, whereas BP II markedly stimulated cholesteryl ester formation, and BP III caused no difference in response vs normal fibroblasts. However, in cultured normal human monocyte macrophages, BP III, but not BP I or BP II, stimulated cholesteryl esterification two- to threefold. BP I, BP II, and BP III may provide new insights into normal metabolism of lipids, lipoproteins, and free fatty acids and the pathophysiology of hyperapoB.
Kwiterovich
P O
PO
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD.
Motevalli
M
M
Miller
M
M
Bachorik
P S
PS
Kafonek
S D
SD
Chatterjee
S
S
Beaty
T
T
Virgil
D
D
D000818:Animals; D001053:Apolipoproteins / Q000097:blood / Q000502:physiology*; D001055:Apolipoproteins B / Q000097:blood / Q000235:genetics; D001798:Blood Proteins / Q000502:physiology*; D015926:Complement C3a / Q000031:analogs & derivatives*; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006951:Hyperlipoproteinemias / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008074:Lipoproteins / Q000097:blood / Q000235:genetics / Q000502:physiology*
D001053:Apolipoproteins; D001055:Apolipoproteins B; D001798:Blood Proteins; D008074:Lipoproteins; C044541:complement C3a, des-Arg-(77)-; D015926:Complement C3a