The effects of altered apolipoprotein A-I structure on plasma HDL concentration. Trends Cardiovasc Med 2002 Apr;12(3):121-8
Date
05/15/2002Pubmed ID
12007737DOI
10.1016/s1050-1738(01)00163-3Scopus ID
2-s2.0-0036234218 (requires institutional sign-in at Scopus site) 171 CitationsAbstract
Approximately 46 human apolipoprotein A-I (apoA-I) coding sequence mutations have been reported to date. Roughly half of these mutations are associated with lower than average plasma concentrations of high-density lipoprotein (HDL) apoA-I. Mutations associated with low HDL apoA-I concentrations fall into two main categories: those which poorly activate the enzyme lecithin:cholesterol acyltransferase (LCAT) and those associated with amyloidosis. These phenotypically distinct groups of mutations are uniquely localized in different regions of the apoprotein sequence. Mutations associated with abnormal LCAT activation are located within repeats 5, 6, and 7, corresponding to amino acids 121 to 186, while many of the mutations found in amyloid deposits are clustered at the amino terminus of the protein, namely residues 1 to 90. These observations strongly support the idea that the tertiary structure of apoA-I determines its intravascular fate and ultimately the steady state concentration of plasma HDL.
Author List
Sorci-Thomas MG, Thomas MJAuthors
Mary Sorci Thomas PhD Professor in the Medicine department at Medical College of WisconsinMichael J. Thomas PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAmino Acids
Amyloidosis
Apolipoprotein A-I
Enzyme Activation
Humans
Lipoproteins, HDL
Mutation
Phosphatidylcholine-Sterol O-Acyltransferase
Sequence Homology, Amino Acid
