Circulation, Vol 82, 1574-1594, Copyright © 1990 by American Heart Association
SG Young
For the past 5 years, investigators from many different laboratories have
contributed to a greatly increased understanding of two very important
lipid-carrying proteins in plasma--apo B-100 and apo B-48. Apo B-100, an
extremely large protein composed of 4,536 amino acids, is synthesized by
the liver and is crucial for the assembly of triglyceride-rich VLDL
particles. Apo B-100 is virtually the only protein of LDL, a cholesteryl
ester-enriched class of lipoproteins that are metabolic products of VLDL.
The apo B-100 of LDL serves as a ligand for the LDL receptor-mediated
uptake of LDL particles by the liver and extrahepatic tissues. The LDL
receptor-binding region of apo B-100 is located in the carboxyterminal
portion of the molecule, whereas its lipid-binding regions appear to be
broadly dispersed throughout its length. Apo B-48 contains the
amino-terminal 2,152 amino acids of apo B- 100 and is produced by the
intestine as a result of editing of a single nucleotide of the apo B mRNA,
which changes the codon specifying apo B- 100 amino acid 2,153 to a
premature stop codon. Apo B-48 has an obligatory structural role in the
formation of chylomicrons; therefore, its synthesis is essential for
absorption of dietary fats and fat- soluble vitamins. Both apo B-48 and apo
B-100 are encoded on chromosome 2 by a single gene that contains 29 exons
and 28 introns. An elevated level of apo B-100 in the plasma is a potent
risk factor for developing premature atherosclerotic disease. In the past 3
years, many different apo B gene mutations that affect the concentrations
of both apo B and cholesterol in the plasma have been characterized. A
missense mutation in the codon for apo B-100 amino aid 3,500 is associated
with hypercholesterolemia. This mutation results in poor binding of apo B-
100 to the LDL receptor, thereby causing the cholesteryl ester-enriched LDL
particles to accumulate in the plasma. This disorder is called familial
defective apo B-100, and it is probably a cause of premature
atherosclerotic disease. Familial hypobetalipoproteinemia is a condition
associated with abnormally low levels of apo B and cholesterol; affected
individuals may actually have a reduced risk of atherosclerotic
disease.(ABSTRACT TRUNCATED AT 400 WORDS)
ARTICLES
Recent progress in understanding apolipoprotein B
Department of Medicine, University of California, San Francisco 94140- 0608.
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