Linked Life Data

9507105

Source:http://linkedlifedata.com/resource/pubmed/id/9507105

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-4-30
pubmed:abstractText
Characterization of the factors that regulate plasma cholesterol esterification shows that the increased activity of lecithin:cholesterol acyltransferase (LCAT) in the plasma of hyperlipidemic subjects is due to enhanced interactions with a preferred substrate. The details of how the physical properties of high density lipoproteins (HDL) may affect their ability to stimulate cholesterol esterification by LCAT have been investigated in homogeneous reconstituted HDL particles containing two molecules of apolipoprotein (apo) A-I (Lp2A-I) and palmitoyl-oleoyl phosphatidylcholine (POPC). Increasing the POPC or sphingomyelin (SPH) content in an Lp2A-I complex increases particle size and stability but decreases the negative surface charge of apoA-I. Increasing Lp2A-I POPC or SPH content also significantly inhibits cholesterol esterification by LCAT. Increase in the maximum rate of CE production (Vmax) by LCAT is directly related to an increased negative charge on the different Lp2A-I particles and to a reduced amount and stability of amphipathic alpha-helices in apoA-I. In contrast, increasing the Lp2A-I complex negative charge directly by addition of a charged lipid, phosphatidylinositol (PI), has minimal effect on apoA-I conformation and LCAT activation. While variations in Lp2A-I PI content have little effect on the interfacial binding of LCAT, increasing POPC content appears to directly increase the binding affinity of LCAT for the different Lp2A-I particles. These results show that LCAT is stimulated by an apoA-I conformation-dependent increase in negative charge but is less sensitive to electrostatic changes in the lipid interface of discoidal Lp2A-I. The activation of LCAT appears to be dependent on the exposure of both central (residues 98-132) and N-terminal (residues 2-8) domains in apoA-I. A strong relationship between the immunoreactivity of two specific mAbs, 4H1 and A11, and LCAT reactivity suggests that the N-terminus of apoA-I may interact with a central domain in a manner that may regulate the accessibility of LCAT to the edge of the disc. This indicates that the conformation and charge of apoA-I are sensitive to the surface-lipid composition of HDL particles and play a central role in regulating LCAT activation. Since alterations in the surface lipid composition of HDL particles from hyperlipidemic subjects also modify the charge and structure of these particles, this may stimulate the rates of cholesterol esterification by making these lipoproteins preferred LCAT substrates.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-3002
pubmed:author
pubmed:copyrightInfo
Copyright 1998 Elsevier Science B.V.
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
1390
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
160-72
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9507105-Apolipoprotein A-I, pubmed-meshheading:9507105-Cholesterol, pubmed-meshheading:9507105-Cholesterol Esters, pubmed-meshheading:9507105-Enzyme Activation, pubmed-meshheading:9507105-Humans, pubmed-meshheading:9507105-Kinetics, pubmed-meshheading:9507105-Lipoproteins, HDL, pubmed-meshheading:9507105-Models, Molecular, pubmed-meshheading:9507105-Particle Size, pubmed-meshheading:9507105-Phosphatidylcholine-Sterol O-Acyltransferase, pubmed-meshheading:9507105-Phosphatidylcholines, pubmed-meshheading:9507105-Phosphatidylinositols, pubmed-meshheading:9507105-Protein Conformation, pubmed-meshheading:9507105-Protein Structure, Secondary, pubmed-meshheading:9507105-Sphingomyelins, pubmed-meshheading:9507105-Static Electricity, pubmed-meshheading:9507105-Surface Properties
pubmed:year
1998
pubmed:articleTitle
Effect of the surface lipid composition of reconstituted LPA-I on apolipoprotein A-I structure and lecithin: cholesterol acyltransferase activity.
pubmed:affiliation
Lipoproteins and Atherosclerosis Group, Ottawa Civic Hospital, University of Ottawa Heart Institute H-452, 1053 Carling Avenue, Ottawa, Ont., Canada.
pubmed:publicationType
Journal Article