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Apolipoprotein E1 Lys-146----Glu with type III hyperlipoproteinemia
K Moriyama1, J Sasaki, A Matsunaga
1Department of Internal Medicine, School of Medicine, Fukuoka University, Japan.
Biochimica Et Biophysica Acta
|September 22, 1992
Summary
Researchers discovered a new apolipoprotein E (apo E) variant in hyperlipidemia patients. This apo E variant shows significantly reduced binding to the apo B, E receptor, impacting lipid metabolism.
Area of Science:
- Biochemistry
- Genetics
- Molecular Biology
Background:
- Apolipoprotein E (apo E) plays a crucial role in lipid metabolism and receptor binding.
- Type III hyperlipidemia is a condition associated with apo E abnormalities.
- Isoelectric focusing (IEF) and gene analysis are standard methods for apo E phenotyping.
Observation:
- A discrepancy was noted between apo E phenotypes determined by IEF (E3/E1) and gene analysis (E3/E3) in individuals with type III hyperlipidemia.
- DNA sequencing revealed a specific lysine to glutamic acid substitution at position 146 (Lys-146----Glu) in the affected individuals.
- This substitution results in a gain of negative charge in the apo E protein.
Findings:
- The identified apo E variant (apo E1 Lys-146----Glu) exhibits significantly reduced binding affinity (<10%) to the low-density lipoprotein (LDL) receptor (also known as the apo B, E receptor) on human skin fibroblasts compared to apo E3.
- Site-directed mutagenesis confirmed the role of this specific amino acid substitution in altering receptor binding.
- The study confirms that lysine at position 146 is critical for apo E's interaction with its receptor.
Implications:
- This finding elucidates the molecular basis of a specific apo E variant's dysfunction in hyperlipidemia.
- Understanding this mechanism can contribute to developing targeted therapies for lipid disorders.
- The study highlights the importance of accurate apo E phenotyping for diagnosing and managing hyperlipidemia.