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lecithin-cholesterol acyltransferase (LCAT, phosphatidylcholine-sterol acyltransferase, phospholipid-cholesterol acyltransferase)
Function:
- central enzyme in the extracellular metabolism of plasma lipoproteins, especially in the process of reverse cholesterol transport
- esterifies free cholesterol transported in plasma lipoproteins
- LCAT is the only enzyme found in plasma which catalyzes esterfication of sterols
- cholesterol from peripheral cells is transferred to HDL particles, esterified through the action of LCAT on HDL, & incorporated into the core of the lipoprotein
- cholesterol ester is thereby transported back to the liver
- LCAT facilitates the removal of excess cholesterol from peripheral tissues to the liver
- most cholesterol esters present in plasma are the product of the reaction catalyzed by LCAT in which cholesterol is esterified with the sn-2 fatty acid of phosphatidylcholine
- the resulting cholesteryl esters are packed into the hydrophobic core of lipoproteins
- activity is enhanced by apo A1 & inhibited by apo A2
phosphatidylcholine + a sterol
1-acylglycerophosphocholine + a sterol ester
Structure:
- belongs to the AB hydrolase superfamily, lipase family
Expression:
- LCAT is synthesized in the liver & circulates in plasma as a complex with components of high density lipoprotein (HDL).
Pathology:
- defects in LCAT are the cause of
a) fish-eye disease [MIM:136120]
b) LCAT deficiency [MIM:245900]; also called Norum disease
Interactions
molecular events
Related
apolipoprotein A1 (APOA1)
apolipoprotein A2 (APOA2)
cholesterol
cholesterol ester
high density lipoprotein (HDL)
General
cholesterol acyltransferase (sterol-O-acyltransferase, acyl coenzyme A:cholesterol acyltransferase 1, acyl-cholesterol acyltransferase, SOAT1 ACACT ACACT1 ACAT ACAT1 SOAT STAT)
glycoprotein
lecithin acyltransferase
plasma protein
Properties
SIZE: entity length = 440 aa
MW = 50 kD
COMPARTMENT: cellular membrane
MOTIF: signal sequence {1-24}
N-glycosylation site {N44}
cysteine residue {C74}
MODIFICATION: cysteine residue {C98}
cysteine residue {C98}
MODIFICATION: cysteine residue {C74}
N-glycosylation site {N108}
serine residue {S205}
N-glycosylation site {N296}
cysteine residue {C337}
MODIFICATION: cysteine residue {C380}
cysteine residue {C380}
MODIFICATION: cysteine residue {C337}
N-glycosylation site {N408}
Thr glycosylation site {T431}
Ser glycosylation site {S433}
Database Correlations
OMIM correlations
MORBIDMAP 606967
UniProt P04180
Pfam PF02450
Kegg hsa:3931
ENZYME 2.3.1.43
References
- Primary Hyperlipoproteinemias, Steiner & Shafrir
(eds), McGraw Hill, NY, 1991, pg 30
- Tietz Textbook of Clinical Chemistry, 2nd ed. Burtis CA &
Ashwood ER (eds), WB Saunders Co, Philadelphia PA, 1993,
pg 1029
- OMIM :accession 245900
- UniProt :accession P04180
- GeneReviews
https://www.genecards.org/cgi-bin/carddisp.pl?gene=LCAT
- Wikipedia, Lecithin-cholesterol acyltransferase entry
http://en.wikipedia.org/wiki/Lecithin-cholesterol_acyltransferase