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Current Opinion in Lipidology Apr 1998Extensive manipulation of the apolipoprotein B gene in yeast and bacterial artificial chromosome clones and subsequent expression of these clones in transgenic mice have... (Review)
Review
Extensive manipulation of the apolipoprotein B gene in yeast and bacterial artificial chromosome clones and subsequent expression of these clones in transgenic mice have provided fresh insights into several aspects of apolipoprotein B biology, including the identification of sequences important for lipoprotein (a) assembly, the demonstration that intestinal expression of apolipoprotein B is controlled by DNA sequences > 50 kb from the gene, and the extraordinary finding that apolipoprotein B is expressed in the heart.
Topics: Animals; Apolipoproteins B; Chromosomes, Bacterial; Cloning, Molecular; Cysteine; Enhancer Elements, Genetic; Gene Expression Regulation; Intestinal Mucosa; Lipoprotein(a); Mice; Mice, Transgenic; Myocardium; Rec A Recombinases
PubMed: 9559266
DOI: 10.1097/00041433-199804000-00005 -
Annales de Biologie Clinique 1990
International Federation of Clinical Chemistry (IFCC) Scientific Division. Committee on Apolipoproteins, Working Group on Antibody Reagents. Selection and characterization of monoclonal antibodies for measuring plasma levels of apolipoproteins A-I and B.
Topics: Antibodies, Monoclonal; Antibody Affinity; Antibody Specificity; Apolipoproteins A; Apolipoproteins B; Arteriosclerosis; Humans; Polymorphism, Genetic
PubMed: 2288449
DOI: No ID Found -
Biochemical Society Transactions May 1992
Topics: Apolipoprotein B-100; Apolipoproteins B; Apolipoproteins E; Carbon Isotopes; Female; Gas Chromatography-Mass Spectrometry; Humans; Isotope Labeling; Leucine; Lipoproteins, VLDL; Male; Reference Values
PubMed: 1397512
DOI: 10.1042/bst020102s -
Atherosclerosis Aug 1998Retention of apo B-100 lipoproteins, low density lipoprotein (LDL) and probably lipoprotein(a), Lp(a), by intima proteoglycans (PGs) appears to increase the residence... (Review)
Review
Retention of apo B-100 lipoproteins, low density lipoprotein (LDL) and probably lipoprotein(a), Lp(a), by intima proteoglycans (PGs) appears to increase the residence time needed for their structural, hydrolytic and oxidative modifications. If the rate of LDL entry exceeds the tissue capacity to eliminate the modified products, this process may be a contributor to atherogenesis and lesion advancement. LDL binds to PGs of the intima, by association of specific positive segments of the apo B-100 with the negatively-charged glycosaminoglycans (GAGs) made of chondroitin sulfate (CS), dermatan sulfate (DS) and probably heparan sulfate (HS). Small, dense LDL has a higher affinity for CS-PGs than large buoyant particles, probably because they expose more of the segments binding the GAGs than larger LDL. PGs cause irreversible structural alterations of LDL that potentiate hydrolytic and oxidative modifications. These alterations also increase LDL uptake by macrophages and smooth muscle cells. These in vitro data suggest that part of the atherogenicity of LDL may depend on its tendency to form complexes with arterial PGs in vivo. Ex vivo results support this hypothesis. Subjects with coronary heart disease have LDL with significantly higher affinity for arterial PGs. This is also a characteristic of subjects with the atherogenic lipoprotein phenotype, with high levels of small, dense LDL. The LDL-PG affinity, however can be modified by dietary or pharmacological interventions that change the composition and size of LDL. Lesion-prone intima contain PGs with a high affinity for LDL. Increased LDL entrapment at these sites may be a key step in a cyclic atherogenic process.
Topics: Amino Acid Sequence; Animals; Apolipoproteins B; Arteries; Arteriosclerosis; Humans; Lipoproteins; Molecular Sequence Data; Proteoglycans
PubMed: 9712326
DOI: 10.1016/s0021-9150(98)00107-5 -
Clinical Chemistry Oct 2004Plasma lipoproteins are important determinants of atherosclerosis. Apolipoprotein (apo) B is a large, amphipathic glycoprotein that plays a central role in human... (Review)
Review
BACKGROUND
Plasma lipoproteins are important determinants of atherosclerosis. Apolipoprotein (apo) B is a large, amphipathic glycoprotein that plays a central role in human lipoprotein metabolism. Two forms of apoB are produced from the APOB gene by a unique posttranscriptional editing process: apoB-48, which is required for chylomicron production in the small intestine, and apoB-100, required for VLDL production in the liver. In addition to being the essential structural component of VLDL, apoB-100 is the ligand for LDL-receptor-mediated endocytosis of LDL particles.
CONTENT
The study of monogenic dyslipidemias has revealed important aspects of metabolic pathways. In this review, we discuss the regulation of apoB metabolism and examine how APOB gene defects can lead to both hypo- and hypercholesterolemia. The key clinical, metabolic, and genetic features of familial hypobetalipoproteinemia and familial ligand-defective apoB-100 are described.
SUMMARY
Missense mutations in the LDL-receptor-binding domain of apoB cause familial ligand-defective apoB-100, characterized by hypercholesterolemia and premature coronary artery disease. Other mutations in APOB can cause familial hypobetalipoproteinemia, characterized by hypocholesterolemia and resistance to atherosclerosis. These naturally occurring mutations reveal key domains in apoB and demonstrate how monogenic dyslipidemias can provide insight into biologically important mechanisms.
Topics: Apolipoproteins B; Humans; Hyperlipidemias; Mutation
PubMed: 15308601
DOI: 10.1373/clinchem.2004.038026 -
Nutrition Reviews Nov 1990
Review
Topics: Apolipoproteins B; Cell Line; Humans; Oleic Acid; Oleic Acids
PubMed: 2080046
DOI: 10.1111/j.1753-4887.1990.tb02894.x -
Biokhimiia (Moscow, Russia) Sep 1995Biosynthesis of cholesterol esters in the blood flow and their function are determined by the fact that these compounds are the sole endogenously synthesized molecules... (Review)
Review
Biosynthesis of cholesterol esters in the blood flow and their function are determined by the fact that these compounds are the sole endogenously synthesized molecules whose hydrophobicity is higher than that of triglycerides transferred by the blood. Within the structure of intermediate density lipoproteins, cholesterol esters substitute for triglycerides during association of apoprotein B-100 with the C-terminal lipid-binding domain. Substitution of the liquid-crystalline phase of triglycerides for the corresponding phase of cholesterol esters results in a significant alteration of the apoprotein B-100 conformation and the formation of low density lipoproteins. Within the structure of low density lipoproteins, the N-terminal domain (apoprotein B-100 ligand) acquires an active conformation and an ability to interact with cell membrane receptors, thereby facilitating their absorption of low density lipoproteins. Cholesterol synthesis in the blood is an independent step in triglyceride transport. Inhibition of cholesterol ester synthesis into high density lipoproteins and their conversion into intermediate density lipoproteins is unaccompanied by the acquisition by apoprotein B-100 of a final conformation or by the formation of low density lipoproteins. Remnants of intermediate density lipoproteins having an intermediate conformation of apoprotein B-100 and the inactive position of the domain ligand are accumulated in the blood. This results in the development of IIb type hyperlipoproteinemia. Resumption of conversion of cholesterol esters from high density lipoproteins into intermediate density lipoprotein remnants normalizes the triglyceride transport. The final conformation of apoprotein B-100 can be modelled by substituting triglycerides in intermediate density lipoprotein remnants for another substance whose hydrophobicity is similar to that of cholesterol esters (dolichol, probucol).(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Anticholesteremic Agents; Apolipoprotein B-100; Apolipoproteins B; Biological Transport; Cholesterol Esters; Lipolysis; Probucol; Protein Conformation; Triglycerides
PubMed: 8562646
DOI: No ID Found -
Biochemical Society Transactions Apr 1987
Review
Topics: Amino Acid Sequence; Apolipoproteins B; Base Sequence; DNA; Humans; Lipoproteins, LDL; Lipoproteins, VLDL; Molecular Weight; Protein Conformation; Receptors, LDL
PubMed: 3556259
DOI: 10.1042/bst0150195 -
Metabolism: Clinical and Experimental Oct 1996We describe a new truncation of apolipoprotein (apo) B in a white kindred with familial hypobetalipoproteinemia (FHBL). Apo B-43.7, found in a daughter and her father,...
We describe a new truncation of apolipoprotein (apo) B in a white kindred with familial hypobetalipoproteinemia (FHBL). Apo B-43.7, found in a daughter and her father, was due to a C --> T change in base position 6162 of the apo B gene converting the arginine (residue 1986) codon CGA to a stop codon TGA. Both subjects were heterozygotes, and both apo B-43.7- and apo B-100-containing particles were present in plasma. On density gradient ultracentrifugation (DGUC), approximately 30% to 40% of apo B-43.7 floated with very-low-density lipoprotein (VLDL)/intermediate-density lipoprotein (IDL)-density particles and 60% to 70% floated with high-density lipoprotein (HDL)-density particles. To assess the metabolism of apo B, 13C-leucine was infused and its rates of appearance in and disappearance from apo B-43.7- and apo B-100-containing particles were quantified by multicompartmental kinetic analysis. Apo B-100 entered plasma via VLDL with a production rate of 30 mg x kg-1 x d-1. Fractional catabolic rates (FCRs) for apo B-100 VLDL, IDL, and low-density lipoprotein (LDL) were 20.0, 16.0, and 0.46 pools x d-1, respectively. The production rate of apo B-43.7 was 9.6 mg x kg-1 x d-1, and FCRs for apo B-43.7 VLDL- and HDL-like particles were 12.0 and 1.8 pools x d-1, respectively. Approximately 30% of apo B-43.7 in HDL-density particles was derived from VLDL apo B-43.7, and about 70% appeared to enter the plasma as HDLs. The relatively low production rate of apo B-43.7 is compatible with previous reports that apo B truncations are produced at lower rates than their apo B-100 counterparts.
Topics: Adult; Apolipoprotein B-100; Apolipoproteins B; Child; Female; Humans; Hypobetalipoproteinemias; Lipoproteins; Male; Middle Aged; Mutation; Pedigree
PubMed: 8843188
DOI: 10.1016/s0026-0495(96)90251-6 -
The Journal of Biological Chemistry Jul 1986The structural relationship between apolipoprotein B-100 (apo-B-100) and apolipoprotein B-48 (apo-B-48) has not been elucidated. A peptide fragment (MDB-18) of... (Comparative Study)
Comparative Study
The structural relationship between apolipoprotein B-100 (apo-B-100) and apolipoprotein B-48 (apo-B-48) has not been elucidated. A peptide fragment (MDB-18) of approximately 6 kDa was isolated from a tryptic digest of apo-B-100. The sequence of the first 22 amino acids of MDB-18 was determined by Edman degradation. A 15-residue peptide corresponding to this sequence was synthesized by the solid-phase method and was utilized to develop a sequence-specific polyclonal antibody. On immunoblot analysis, the antibody recognized both intact apo-B-100 and apo-B-48. In addition, preincubating the antibody with the synthetic peptide abolished the recognition of both apo-B-100 and apo-B-48. These data are interpreted as indicating that there is an amino acid sequence homology between apo-B-100 and apo-B-48. Since the MDB-18 peptide is located in the carboxyl region of the B-100 molecule, we propose apo-B-100 and apo-B-48 share a common carboxyl region sequence.
Topics: Amino Acid Sequence; Apolipoprotein B-100; Apolipoprotein B-48; Apolipoproteins B; Humans; Immunologic Techniques; Peptide Fragments; Trypsin
PubMed: 3522585
DOI: No ID Found