• Lacko, Andras (PI)

Project Details


The proposed research will examine the mechanism of the reaction catalyzed
by the enzyme Lecithin: Cholesterol Acyltransferase (LCAT). Interaction
between the enzyme and high density lipoprotein (HDL), its primary
substrate in vivo, will be investigated. A newly developed method
involving hydrophobic chromatography will be used for the isolation of
HDL. This technique avoids some of the compositional changes that are
associated with other preparative techniques, particularly
ultracentrifugation. The HDL will be fractionated on DEAE cellulose into
subfractions which are known to exhibit differential reactivity toward
LCAT. Specific phases of the proposed research will include:

1) Incubation of the HDL subfractions with purified enzyme and examination
of the LCAT reaction as a function of the concentration of substrate lipids
and those of specific apoprotein components of the lipid/protein substrate

2) Study of the transfer of substrate lipids from triglyceride rich
lipoprotein to HDL subfractions and the effect of the attendant changes on
the LCAT reaction.

3) Study of the mechanism of product (lysolecithin) removal from the enzyme

The LCAT/HDL system has been implicated in the process called reverse
cholesterol transport which facilitates the transfer of excess cholesterol
from peripheral tissues to the liver. It is thus likely that the findings
of the research proposed here would aid in the understanding of the
reversal of atherosclerosis. Consequently, the findings may ultimately be
useful in developing modalities for the prevention of cardiovascular
diseases including coronary heart disease.
Effective start/end date31/12/8931/12/89


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