Affinage

LCAT

Phosphatidylcholine-sterol acyltransferase · UniProt P04180

Length
440 aa
Mass
49.6 kDa
Annotated
2026-04-28
100 papers in source corpus 28 papers cited in narrative 28 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LCAT is a liver-secreted plasma phospholipid-cholesterol acyltransferase that esterifies free cholesterol on lipoproteins using the sn-2 fatty acyl chain of phosphatidylcholine, driven by an α/β hydrolase fold with a Ser181/Asp345/His377 catalytic triad, an interfacial recognition lid (residues 50–74), and an oxyanion hole formed by F103 and L182 (PMID:9541390, PMID:26195816). Activated primarily by apoA-I on HDL—through a registry-dependent epitope spanning helices 3–7 of anti-parallel apoA-I rings—and by apoE on apoB-containing lipoproteins, LCAT is essential for converting discoidal pre-β HDL to mature spherical HDL particles downstream of ABCA1-mediated lipidation, and is the exclusive source of long-chain polyunsaturated cholesteryl esters in plasma apoB lipoproteins (PMID:29773713, PMID:15654758, PMID:17206937, PMID:11893779). Loss-of-function mutations cause familial LCAT deficiency or fish-eye disease—the latter reflecting selective loss of α-LCAT (HDL-directed) activity while retaining β-LCAT (LDL-directed) activity—and the resulting accumulation of lipoprotein X (LpX) directly induces glomerulonephropathy through macropinocytic uptake and pro-inflammatory signaling in renal cells (PMID:2052566, PMID:4061122, PMID:26919698, PMID:15466392). LCAT transcription is upregulated by IL-6/STAT3 in hepatocytes and by estrogen via ESR1, linking its expression to inflammatory and hormonal regulation of cholesterol metabolism (PMID:12032172, PMID:38718297).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1985 High

    Establishing that plasma contains two functionally distinct LCAT activities—α-LCAT on HDL and β-LCAT on VLDL/LDL—resolved how fish-eye disease patients lose HDL esterification while retaining LDL esterification, defining substrate selectivity as a fundamental LCAT property.

    Evidence In vitro cross-incubation of normal and fish-eye plasma LCAT with isolated HDL fractions, with biochemical cholesterol esterification measurements

    PMID:3989387 PMID:4061122

    Open questions at the time
    • Molecular basis of α- vs. β-LCAT selectivity unknown at this stage
    • No structural information on LCAT or its activator interactions
  2. 1991 High

    Identification of the T123I missense mutation as the genetic cause of fish-eye disease provided the first molecular explanation for selective α-LCAT deficiency and localized substrate discrimination to a specific region of the LCAT polypeptide.

    Evidence PCR sequencing of LCAT exons in two unrelated fish-eye disease families with biochemical validation of selective HDL-activity loss

    PMID:2052566

    Open questions at the time
    • Structural context of T123 unknown
    • Mechanism by which T123I selectively impairs HDL activity not yet determined
  3. 1997 High

    Complete LCAT knockout in mice proved that LCAT is essential for virtually all plasma cholesterol esterification and HDL maturation in vivo, establishing the physiological non-redundancy of this enzyme.

    Evidence Targeted gene disruption in mouse ES cells with comprehensive plasma lipoprotein phenotyping showing 99% loss of esterification and HDL-C reduced to 7% of normal

    PMID:9054454

    Open questions at the time
    • Downstream pathological consequences of LCAT deficiency (renal, corneal) not yet modeled
    • Relative contributions of α- vs. β-LCAT in vivo unclear
  4. 1998 High

    Structural modeling and mutagenesis revealed that LCAT belongs to the α/β hydrolase fold superfamily with a Ser/Asp/His catalytic triad and an interfacial lid domain (residues 50–74), providing the first mechanistic framework for its catalytic cycle and substrate engagement.

    Evidence Threading/homology modeling combined with site-directed mutagenesis of D345, H377, F103, L182 in COS-1 cells with in vitro activity assays

    PMID:10065713 PMID:9541390

    Open questions at the time
    • No experimental 3D structure yet
    • Lid dynamics during catalysis uncharacterized
  5. 2000 High

    Mechanistic dissection of fish-eye disease mutations showed they specifically ablate phospholipase A2 activity on HDL, explaining how a single enzyme can exhibit substrate-selective loss of function depending on the activating apolipoprotein context.

    Evidence Expression of T123I, N131D, N391S, F382 LCAT mutants in COS-1 cells with esterase, PLA2, and acyltransferase assays on monomeric substrates, rHDL, and LDL

    PMID:10669643 PMID:10787436

    Open questions at the time
    • Structural basis for apoA-I vs. apoE interaction surfaces not resolved
    • In vivo validation of PLA2 selectivity mechanism absent
  6. 2002 High

    Demonstration that LCAT is the exclusive source of long-chain polyunsaturated cholesteryl esters in apoB lipoproteins, and that residue E149 shapes fatty-acyl selectivity, established LCAT's quantitative contribution to the plasma CE fatty acid composition.

    Evidence LCAT-null crossed into LDLr-/- and apoE-/- backgrounds with CE fatty acid profiling by GLC; transgenic E149A mutant in LCAT-null mice

    PMID:11590219 PMID:11893779

    Open questions at the time
    • Structural basis for E149-mediated fatty acyl selection unknown
    • Physiological consequences of altered CE fatty acid composition not determined
  7. 2005 High

    Identifying apoE as the major LCAT activator on apoB lipoproteins and negative charges in apoA-I helix 6 as modulators of catalytic efficiency defined how different apolipoprotein cofactors tune LCAT activity on distinct lipoprotein substrates.

    Evidence Genetic mouse models (apoE-/-, apoA-I-/-, double KO) with in vitro LCAT incubation; systematic apoA-I helix-6 charge mutants with kinetic analysis on reconstituted HDL

    PMID:15654758 PMID:15807534

    Open questions at the time
    • Physical interaction surfaces between LCAT and apoE not mapped
    • Whether apoE activates LCAT through a mechanism analogous to apoA-I's registry mechanism unknown
  8. 2007 High

    Showing that LCAT converts apoE-containing discoidal HDL to spherical particles in apoA-I-null mice, dependent on ABCA1, placed LCAT in the HDL maturation pathway downstream of transporter-mediated lipidation.

    Evidence Adenoviral co-expression of apoE and LCAT in apoA-I-/- and ABCA1-/- mice with electron microscopy and FPLC analysis

    PMID:17206937

    Open questions at the time
    • Kinetics of LCAT action on nascent vs. remodeled HDL in vivo not quantified
    • Role of other HDL remodeling enzymes (CETP, PLTP) in this process not dissected
  9. 2015 High

    The 2.65 Å crystal structure of human LCAT confirmed the α/β hydrolase core, revealed two accessory subdomains mediating interfacial activation and lid function, and allowed mapping of all known disease mutations onto a validated three-dimensional framework.

    Evidence X-ray crystallography after deglycosylation and Fab co-crystallization

    PMID:26195816

    Open questions at the time
    • No structure of LCAT bound to a lipoprotein or apoA-I
    • Lid conformational dynamics during catalysis not captured
  10. 2016 High

    Direct demonstration that LpX is nephrotoxic—causing glomerular deposition, macropinocytic uptake by podocytes and mesangial cells, and IL-6 secretion—provided the causal link between LCAT deficiency, LpX accumulation, and the characteristic renal disease.

    Evidence Synthetic LpX infusion into Lcat-/- vs. WT mice; in vitro podocyte/mesangial cell uptake assays; TEM/SEM; proteinuria measurement

    PMID:15466392 PMID:26919698

    Open questions at the time
    • Signaling pathways downstream of LpX uptake not fully characterized
    • Whether LpX clearance therapy can reverse established nephropathy unknown
  11. 2018 High

    The apoA-I 'thumbwheel' mechanism revealed that LCAT activation requires a specific inter-chain registry (5/5) presenting a composite epitope from helices 3–7 on the two antiparallel apoA-I molecules, explaining how HDL conformation controls LCAT activity independently of binding.

    Evidence Engineered disulfide-locked apoA-I registries on reconstituted discoidal HDL with LCAT activity assays and chemical cross-linking

    PMID:29773713

    Open questions at the time
    • Atomic-resolution structure of the LCAT–apoA-I–HDL ternary complex not available
    • Whether the thumbwheel mechanism operates on spherical HDL or only on nascent discs is unknown
  12. 2021 High

    In vivo tracer kinetics revealed that LCAT associates preferentially with medium and small HDL subfractions and appears on HDL with delayed kinetics compared with PLTP and CETP, suggesting a distinct metabolic itinerary possibly involving an extravascular transit.

    Evidence Stable-isotope leucine tracer infusion with targeted mass spectrometry and compartmental modeling in six human subjects

    PMID:33351780

    Open questions at the time
    • Site of extravascular LCAT residence not identified
    • Whether delayed HDL association reflects hepatic secretion kinetics or peripheral redistribution is unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • A high-resolution structure of the LCAT–apoA-I–HDL ternary complex, the conformational dynamics of the lid during catalysis, and the precise signaling pathways by which LpX causes glomerular injury remain unresolved.
  • No atomic structure of LCAT engaged with a lipoprotein particle
  • Lid dynamics during the catalytic cycle uncharacterized at atomic resolution
  • Downstream intracellular signaling from LpX macropinocytosis incompletely mapped

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 9 GO:0008289 lipid binding 2 GO:0016787 hydrolase activity 2
Localization
GO:0005576 extracellular region 4 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-1430728 Metabolism 6 R-HSA-1643685 Disease 4 R-HSA-382551 Transport of small molecules 3
Partners
ABCA1APOA1APOA2APOELDLRSCARB1

Evidence

Reading pass · 28 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 LCAT belongs to the α/β hydrolase fold family and employs a Ser/Asp/His catalytic triad. Site-directed mutagenesis identified D345 and H377 as catalytic residues and F103 and L182 as oxyanion hole residues. A putative 'lid' domain at residues 50–74 was proposed to mediate enzyme-substrate interaction. Threading/structural homology modeling combined with site-directed mutagenesis and in vitro activity assays in COS-1 cells Protein Science High 9541390
2015 The 2.65 Å crystal structure of human LCAT reveals an α/β hydrolase core with two additional subdomains: subdomain 1 contains the interfacial activation region and subdomain 2 contains the lid and substrate-binding pocket residues. Natural loss-of-function mutations map onto these structural features. X-ray crystallography (2.65 Å) after enzymatic deglycosylation and Fab-fragment co-crystallization Journal of Lipid Research High 26195816
1999 Residues 50–74 of LCAT constitute an interfacial recognition domain (lid) required for substrate interaction. Deletion of residues 56–68 abolished all activity; W61 requires an aromatic residue for full activity on HDL; R52 and K53 contribute to lid folding and activity on both HDL and LDL; M65/N66 are required for membrane-destabilizing (fusogenic) properties of the lid peptide. Site-directed mutagenesis, synthetic peptide membrane-fusion assays, in vitro enzyme activity on HDL and LDL substrates Protein Engineering High 10065713
2000 Fish-eye disease (FED) LCAT mutants T123I, N131D, and N391S specifically lose phospholipase A2 activity on HDL, accounting for their selective loss of acyltransferase activity on HDL while retaining activity on LDL. Residues T123 and F382, located N-terminal of amphipathic helices α3-4 and αHis, specifically mediate LCAT interaction with HDL and apoA-I. Expression of natural and engineered LCAT mutants in COS-1 cells; esterase, phospholipase A2, and acyltransferase activity assays on monomeric substrate, rHDL, and LDL Journal of Lipid Research High 10787436
1991 A homozygous T123I missense mutation in LCAT causes selective loss of α-LCAT activity (activity on HDL) while preserving β-LCAT activity (activity on VLDL/LDL), establishing the molecular basis of fish-eye disease as a substrate-selective enzyme defect. PCR sequencing of LCAT exons; family analysis; biochemical characterization of plasma LCAT activity on HDL vs. VLDL/LDL substrates Proceedings of the National Academy of Sciences USA High 2052566
1985 Two distinct LCAT activities exist in normal plasma: α-LCAT, specific for HDL, and β-LCAT, specific for VLDL/LDL. Fish-eye disease is characterized by selective α-LCAT deficiency, as demonstrated by the inability of fish-eye plasma LCAT to esterify HDL cholesterol while normal LCAT fully esterified fish-eye HDL cholesterol in vitro. In vitro incubations of isolated HDL fractions with normal vs. fish-eye LCAT (lipoprotein-depleted plasma); cholesterol esterification measured biochemically Acta Medica Scandinavica High 4061122
2018 APOA1 uses a 'thumbwheel' mechanism to activate LCAT: the anti-parallel APOA1 rings on nascent discoidal HDL can adopt two registries (5/5 and 5/2). Locking APOA1 in the 5/2 registry by engineered disulfide bonds impaired LCAT cholesteryl esterification activity despite equal LCAT binding, demonstrating that full LCAT activation requires a hybrid epitope composed of helices 5–7 on one APOA1 molecule and helices 3–4 on the other. Engineered cysteine disulfide cross-linking to lock APOA1 in specific registries; LCAT esterification activity assay; chemical cross-linking; cholesterol efflux assay Journal of Lipid Research High 29773713
2005 ApoE is the major physiological activator of LCAT on apoB-containing lipoproteins (VLDL/LDL). Deletion of apoE from LDL nearly abolishes LCAT-mediated cholesterol esterification on those particles; adding apoE to apoE/apoA-I double-knockout VLDL restores 3-fold more LCAT activity than adding apoA-I. Genetic mouse models (apoE-/-, apoA-I-/-, double KO); plasma CER measurement; recombinant mouse LCAT incubation with isolated LDL from different genotypes; Western blot Biochemistry High 15654758
2005 Negatively charged residues in apoA-I helix 6 directly attenuate LCAT catalytic efficiency: an inverse correlation (r = 0.85) exists between LCAT catalytic efficiency and net negative charge on helix 6, independent of overall particle charge. Engineering of apoA-I helix-6 charge mutants; reconstituted HDL of two discrete sizes; LCAT kinetic assays (Km, Vmax, catalytic efficiency) Biochemistry High 15807534
1997 Complete genetic knockout of LCAT in mice eliminates plasma cholesterol esterification (99% reduction in activity), reduces HDL cholesterol to 7% of normal, elevates triglycerides, and produces heterogeneous prebeta-migrating HDL, establishing that LCAT is essential for HDL maturation and plasma cholesterol esterification in vivo. Targeted gene disruption in mouse embryonic stem cells; plasma lipid/lipoprotein analysis by FPLC and 2D gel electrophoresis; LCAT activity assays Journal of Biological Chemistry High 9054454
2007 LCAT is essential for the conversion of discoidal HDL to spherical HDL in vivo. In apoA-I-/- mice, adenovirus-mediated apoE expression generates discoidal HDL; co-expression of human LCAT converts these to spherical particles and normalizes lipoprotein profiles, demonstrating that LCAT acts downstream of ABCA1-dependent lipidation. Adenovirus-mediated gene transfer in apoA-I-/- and ABCA1-/- mice; lipoprotein analysis by FPLC and electron microscopy Biochemical Journal High 17206937
2016 Lipoprotein X (LpX), an abnormal cholesterol-rich multilamellar particle that accumulates in LCAT deficiency, is directly nephrotoxic. An apoA-I- and LCAT-dependent pathway normally converts LpX to HDL-like particles for plasma clearance. In Lcat-/- mice, exogenous LpX deposited in all glomerular compartments, was taken up by macropinocytosis into endothelial cells, podocytes, and mesangial cells, induced IL-6 secretion, and recapitulated all histological hallmarks of familial LCAT deficiency nephropathy. Synthetic LpX administration to wild-type and Lcat-/- mice; in vitro podocyte and mesangial cell experiments; TEM/SEM; immunohistochemistry; proteinuria measurement; lysosomal PLA2 degradation assays PLoS ONE High 26919698
1987 The LCAT structural gene maps to chromosome 16q22, confirmed by somatic cell hybrid analysis and in situ hybridization. Southern blotting of rodent × human somatic cell hybrids; in situ hybridization to human metaphase chromosomes Annals of Human Genetics High 3674753
1995 Glycation of apoA-I lysine residues on HDL reduces LCAT reactivity: moderate glycation increases both Km and Vmax but decreases enzyme reactivity, while high glycation decreases both parameters. Native diabetic HDL also impairs LCAT Vmax and reactivity, implicating glycation of the LCAT cofactor apoA-I as a mechanism of reduced LCAT activity in diabetes. In vitro HDL glycation with glucose/cyanoborohydride; LCAT kinetic assays (Km, Vmax) with glycated vs. native HDL substrates; TNBS quantification of glycated residues Clinica Chimica Acta Medium 7758222
1993 ApoA-I is the most efficient LCAT activator among apolipoproteins: phospholipid-cholesterol complexes with intact apoA-I show ~40-fold greater LCAT catalytic efficiency than those with apoA-I CNBr fragments; apoA-II gives lowest efficiency. LCAT action on discoidal complexes drives their conversion to spherical particles with a cholesteryl ester core. In vitro LCAT kinetic assays on reconstituted complexes with apoA-I, apoA-I fragments, apoA-II, and apoA-IV; electron microscopy of product particles Biochimica et Biophysica Acta Medium 1420299
1985 LCAT action on HDL3 in the presence of triglyceride-rich lipoproteins drives conversion of HDL3 to HDL2b in vitro. Removal of VLDL/LDL prevents this conversion, and HDL3 shifts toward higher density instead; addition of exogenous triglyceride-rich lipoproteins restores HDL3→HDL2b conversion in an LCAT-dependent manner. In vitro incubation of whole plasma with selective lipoprotein depletion (phosphotungstate precipitation); analytical ultracentrifugation; LCAT inhibition experiments Journal of Lipid Research Medium 3989387
2002 LCAT is the exclusive source of long-chain polyunsaturated cholesteryl esters in plasma apoB lipoproteins. Removal of functional LCAT from LDLr-/- mice eliminates all cholesteryl species containing >18-carbon polyunsaturated fatty acids from LDL while increasing saturated/monounsaturated CE, demonstrating LCAT's quantitative contribution to the apoB lipoprotein CE fatty acid pool. Genetic crosses of LCAT-/- into LDLr-/- and apoE-/- mouse backgrounds; CE fatty acid composition by gas-liquid chromatography Journal of Lipid Research High 11893779
2001 A single amino acid substitution E149A in human LCAT selectively increases its in vitro and in vivo reactivity toward phosphatidylcholine species containing sn-2 arachidonate, enriching HDL cholesteryl esters with 20:4 and 22:6 n-3 species without altering HDL concentration or size, demonstrating that E149 shapes substrate fatty-acyl selectivity. Transgenic mouse overexpression of hLCAT-E149A vs. hLCAT-wt; HDL CE fatty acid composition; crossed into LCAT knockout background Journal of Lipid Research High 11590219
1993 A tyr83→stop null mutation and a tyr156→asn missense mutation cause compound heterozygous classic LCAT deficiency. In vitro expression of LCAT(tyr156→asn) in HEK-293 cells produced a protein with only 6% of normal mass (rapid catabolism) and no detectable CER, but residual mass retained 30% specific α-LCAT activity, indicating the substitution impairs secretion/stability rather than catalysis per se. DNA sequencing; restriction enzyme analysis; in vitro expression in HEK-293 cells; LCAT mass (ELISA) and activity assays Journal of Lipid Research High 8445342
1995 An LCAT frameshift mutation (G873 deletion, Val264 codon) and a missense mutation Gly344→Ser each abolish LCAT activity and mass in patient plasma. In transfected cells, both mutant proteins are synthesized at normal levels but are retained in the endoplasmic reticulum, fail to be processed to the mature 67 kDa form, and are degraded without secretion, revealing a trafficking/folding defect mechanism. Sequencing; COS-1 and BHK cell transfection; pulse-chase labeling; SDS-PAGE/fluorography; immunocytochemistry; Northern blot Journal of Lipid Research High 8656071
2002 IL-6 transcriptionally upregulates LCAT through a minimal STAT3-binding element at −1514 to −1508 bp in the LCAT promoter. Overexpression of STAT3 significantly enhanced IL-6-induced LCAT promoter activity in HepG2 cells. Sequential deletion promoter-reporter constructs transfected in HepG2 cells; IL-6 treatment; STAT3 overexpression Journal of Lipid Research Medium 12032172
2004 Selective accumulation of LpX in LCAT-knockout/SREBP1a-transgenic mice is sufficient to induce spontaneous glomerulopathy with mesangial expansion, foam cell infiltrates, and tubulointerstitial lipid deposits, providing in vivo causal evidence that LpX mediates LCAT-deficiency nephropathy. Novel mouse model (S+lcat-/-) generated by cross-breeding; FPLC lipoprotein fractionation; electron microscopy; histopathology; immunohistochemistry American Journal of Pathology High 15466392
2010 The N-terminal region of apoA-I around residue S36 is required for LCAT activation. The S36A mutant, found in a hypoalphalipoproteinemia patient, is predominantly monomeric (unlike oligomeric WT) and shows significantly impaired LCAT activation on reconstituted HDL despite normal lipid binding, implicating apoA-I self-association as a factor in LCAT cofactor function. Recombinant S36A apoA-I expression; native gel electrophoresis; chemical cross-linking; sedimentation equilibrium; CD spectroscopy; LCAT activation assay on rHDL Journal of Lipid Research Medium 20884842
2021 LCAT is secreted mainly in medium and small HDL (α2, α3, prebeta) and its appearance on HDL in plasma is markedly delayed compared with PLTP and CETP, suggesting LCAT may reside transiently outside systemic circulation before binding to HDL, defining its distinct metabolic itinerary on HDL subpopulations. In vivo stable-isotope tracer infusion (deuterium-labeled leucine); targeted mass spectrometry on Orbitrap Lumos; compartmental modeling across 6 participants JCI Insight High 33351780
2019 LCAT is expressed by corneal epithelial and endothelial cells (LCAT mRNA detected), while keratocytes contain LCAT protein but lack LCAT mRNA, indicating keratocytes acquire LCAT by uptake from interstitial fluid rather than local synthesis. Immunolocalization; in situ hybridization; RNA sequencing of cultured corneal stromal fibroblasts; Western blot of keratocyte lysates Biomolecules Medium 31779197
2000 LCAT reduces LDL-cholesterol in transgenic rabbits through the LDL receptor (LDLr) pathway: LCAT overexpression increases LDL apoB-100 fractional catabolic rate and reduces LDL-C only in rabbits with at least one functional LDLr allele, not in LDLr-/- rabbits, establishing LDLr-dependent clearance as the mechanism for LCAT's anti-atherogenic LDL-lowering effect. Transgenic rabbit model crossed into Watanabe (LDLr-deficient) background; LDL apoB-100 turnover by isotope tracer; plasma lipid and atherosclerosis quantification Arteriosclerosis, Thrombosis, and Vascular Biology High 10669643
2013 An inhibitory anti-LCAT antibody causes acquired LCAT deficiency and nephrotic syndrome indistinguishable from familial LCAT deficiency. Co-immunoprecipitation and mixing tests confirmed the antibody inhibits LCAT activity; immunohistochemistry detected LCAT along glomerular capillary walls, identifying it as the autoantigen in membranous nephropathy. Steroid treatment eliminated the antibody, restored LCAT activity and HDL, and resolved glomerular lesions. Co-immunoprecipitation; mixing test for inhibitory antibody; immunohistochemistry/immunofluorescence; LCAT activity assay; renal biopsy histology Journal of the American Society of Nephrology High 23620397
2024 Estrogen upregulates LCAT expression in liver via ESR1 in an ESR1-dependent manner; LCAT then facilitates HDL-C production and uptake through LDLR and SCARB1 pathways. Enhanced HDL-C absorption impairs SREBP2 maturation, suppressing cholesterol biosynthesis and dampening HCC cell proliferation. LCAT deficiency abolished estrogen's tumor-suppressive effect in ovariectomized female mice. Transcriptomic analysis; in vitro LCAT overexpression/knockdown with SREBP2 readout; in vivo adenoviral/genetic LCAT manipulation; subcutaneous and orthotopic tumor models; pharmacological inhibition with lovastatin Cancer Research Medium 38718297

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Role of apoA-I, ABCA1, LCAT, and SR-BI in the biogenesis of HDL. Journal of molecular medicine (Berlin, Germany) 297 16501936
1997 The molecular pathology of lecithin:cholesterol acyltransferase (LCAT) deficiency syndromes. Journal of lipid research 260 9162740
1991 A molecular defect causing fish eye disease: an amino acid exchange in lecithin-cholesterol acyltransferase (LCAT) leads to the selective loss of alpha-LCAT activity. Proceedings of the National Academy of Sciences of the United States of America 110 2052566
1981 Lecithin:cholesterol acyltransferase (LCAT) mass; its relationship to LCAT activity and cholesterol esterification rate. Journal of lipid research 105 7320631
1997 Targeted disruption of the mouse lecithin:cholesterol acyltransferase (LCAT) gene. Generation of a new animal model for human LCAT deficiency. The Journal of biological chemistry 101 9054454
1998 A proposed architecture for lecithin cholesterol acyl transferase (LCAT): identification of the catalytic triad and molecular modeling. Protein science : a publication of the Protein Society 86 9541390
2007 Pathway of biogenesis of apolipoprotein E-containing HDL in vivo with the participation of ABCA1 and LCAT. The Biochemical journal 83 17206937
1993 Genetic and phenotypic heterogeneity in familial lecithin: cholesterol acyltransferase (LCAT) deficiency. Six newly identified defective alleles further contribute to the structural heterogeneity in this disease. The Journal of clinical investigation 78 8432868
2002 Altered activities of anti-atherogenic enzymes LCAT, paraoxonase, and platelet-activating factor acetylhydrolase in atherosclerosis-susceptible mice. Journal of lipid research 76 11893784
1994 Modification of LCAT activity and HDL structure. New links between cigarette smoke and coronary heart disease risk. Arteriosclerosis and thrombosis : a journal of vascular biology 74 8305416
1985 Evidence for deficiency of high density lipoprotein lecithin: cholesterol acyltransferase activity (alpha-LCAT) in fish eye disease. Acta medica Scandinavica 72 4061122
2018 A thumbwheel mechanism for APOA1 activation of LCAT activity in HDL. Journal of lipid research 68 29773713
1997 Molecular phylogeny of rodents, with special emphasis on murids: evidence from nuclear gene LCAT. Molecular phylogenetics and evolution 65 9417899
2016 Lipoprotein X Causes Renal Disease in LCAT Deficiency. PloS one 64 26919698
1982 Population-based reference values for lecithin-cholesterol acyltransferase (LCAT). Atherosclerosis 58 7115467
1975 Genetics of LCAT (lecithin: cholesterol acyltransferase) deficiency. Annals of human genetics 55 806250
2015 Role of LCAT in Atherosclerosis. Journal of atherosclerosis and thrombosis 52 26607351
2011 Increased risk of coronary artery disease in Caucasians with extremely low HDL cholesterol due to mutations in ABCA1, APOA1, and LCAT. Biochimica et biophysica acta 51 21875686
1996 Two novel molecular defects in the LCAT gene are associated with fish eye disease. Arteriosclerosis, thrombosis, and vascular biology 50 8620346
2003 Hepatic lipase expression in macrophages contributes to atherosclerosis in apoE-deficient and LCAT-transgenic mice. The Journal of clinical investigation 48 12897204
2012 Very low levels of HDL cholesterol and atherosclerosis, a variable relationship--a review of LCAT deficiency. Vascular health and risk management 46 22701329
1996 Potential gene therapy for lecithin-cholesterol acyltransferase (LCAT)-deficient and hypoalphalipoproteinemic patients with adenovirus-mediated transfer of human LCAT gene. Circulation 45 8901669
1993 Two different allelic mutations in the lecithin:cholesterol acyltransferase (LCAT) gene resulting in classic LCAT deficiency: LCAT (tyr83-->stop) and LCAT (tyr156-->asn). Journal of lipid research 45 8445342
2020 Genetic, biochemical, and clinical features of LCAT deficiency: update for 2020. Current opinion in lipidology 43 32618730
1978 Familial LCAT deficiency. Report of two patients from a Canadian family of Italian and Swedish descent. Scandinavian journal of clinical and laboratory investigation. Supplementum 43 746343
2024 Estrogen Induces LCAT to Maintain Cholesterol Homeostasis and Suppress Hepatocellular Carcinoma Development. Cancer research 42 38718297
1992 An amino acid exchange in exon I of the human lecithin: cholesterol acyltransferase (LCAT) gene is associated with fish eye disease. Biochemical and biophysical research communications 42 1571050
2000 LCAT modulates atherogenic plasma lipoproteins and the extent of atherosclerosis only in the presence of normal LDL receptors in transgenic rabbits. Arteriosclerosis, thrombosis, and vascular biology 41 10669643
1988 Familial LCAT deficiency and fish-eye disease. Journal of inherited metabolic disease 41 3141686
1985 The in vitro formation of HDL2 during the action of LCAT: the role of triglyceride-rich lipoproteins. Journal of lipid research 41 3989387
2003 Effects of intravenous apolipoprotein A-I/phosphatidylcholine discs on LCAT, PLTP, and CETP in plasma and peripheral lymph in humans. Arteriosclerosis, thrombosis, and vascular biology 40 12893687
2005 Apolipoprotein E is the major physiological activator of lecithin-cholesterol acyltransferase (LCAT) on apolipoprotein B lipoproteins. Biochemistry 38 15654758
2015 The high-resolution crystal structure of human LCAT. Journal of lipid research 37 26195816
2000 The bushlike radiation of muroid rodents is exemplified by the molecular phylogeny of the LCAT nuclear gene. Molecular phylogenetics and evolution 37 11083941
2019 Recombinant LCAT (Lecithin:Cholesterol Acyltransferase) Rescues Defective HDL (High-Density Lipoprotein)-Mediated Endothelial Protection in Acute Coronary Syndrome. Arteriosclerosis, thrombosis, and vascular biology 35 30894011
2015 Increased plasma cholesterol esterification by LCAT reduces diet-induced atherosclerosis in SR-BI knockout mice. Journal of lipid research 35 25964513
2012 ApoA-IV promotes the biogenesis of apoA-IV-containing HDL particles with the participation of ABCA1 and LCAT. Journal of lipid research 35 23132909
2022 LCAT- targeted therapies: Progress, failures and future. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 34 35121343
2020 Apigenin, flavonoid component isolated from Gentiana veitchiorum flower suppresses the oxidative stress through LDLR-LCAT signaling pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 34 32504920
2011 High prevalence of mutations in LCAT in patients with low HDL cholesterol levels in The Netherlands: identification and characterization of eight novel mutations. Human mutation 34 21901787
2015 Lack of LCAT reduces the LPS-neutralizing capacity of HDL and enhances LPS-induced inflammation in mice. Biochimica et biophysica acta 33 26170061
2005 Apolipoprotein A-I helix 6 negatively charged residues attenuate lecithin-cholesterol acyltransferase (LCAT) reactivity. Biochemistry 33 15807534
2004 A novel in vivo lecithin-cholesterol acyltransferase (LCAT)-deficient mouse expressing predominantly LpX is associated with spontaneous glomerulopathy. The American journal of pathology 33 15466392
2002 Transgenic overexpression of human lecithin: cholesterol acyltransferase (LCAT) in mice does not increase aortic cholesterol deposition. Atherosclerosis 33 12208474
2002 In vivo contribution of LCAT to apolipoprotein B lipoprotein cholesteryl esters in LDL receptor and apolipoprotein E knockout mice. Journal of lipid research 32 11893779
1995 Reactivity of lecithin-cholesterol acyl transferase (LCAT) towards glycated high-density lipoproteins (HDL). Clinica chimica acta; international journal of clinical chemistry 32 7758222
1978 Lecithin-cholesterol acyltransferase (LCAT) activity in chronic uremia. Kidney international. Supplement 32 278893
2018 Loss of LCAT activity in the golden Syrian hamster elicits pro-atherogenic dyslipidemia and enhanced atherosclerosis. Metabolism: clinical and experimental 31 29526535
2015 A novel protein glycan biomarker and LCAT activity in metabolic syndrome. European journal of clinical investigation 31 26081900
2014 Increased risk of premature coronary artery disease in Egyptians with ABCA1 (R219K), CETP (TaqIB), and LCAT (4886C/T) genes polymorphism. Journal of clinical lipidology 31 25110219
2004 HMG-CoA reductase inhibition reverses LCAT and LDL receptor deficiencies and improves HDL in rats with chronic renal failure. American journal of physiology. Renal physiology 31 15507547
2013 Nephrotic syndrome caused by immune-mediated acquired LCAT deficiency. Journal of the American Society of Nephrology : JASN 29 23620397
2004 ACAT inhibition reverses LCAT deficiency and improves plasma HDL in chronic renal failure. American journal of physiology. Renal physiology 29 15280162
1999 Characterization of functional residues in the interfacial recognition domain of lecithin cholesterol acyltransferase (LCAT). Protein engineering 29 10065713
2019 LCAT, ApoD, and ApoA1 Expression and Review of Cholesterol Deposition in the Cornea. Biomolecules 28 31779197
2008 Therapeutic management of a new case of LCAT deficiency with a multifactorial long-term approach based on high doses of angiotensin II receptor blockers (ARBs). Clinical nephrology 28 18397721
1991 Molecular defect in familial lecithin:cholesterol acyltransferase (LCAT) deficiency: a single nucleotide insertion in LCAT gene causes a complete deficient type of the disease. Biochemical and biophysical research communications 28 1662503
2009 An apoA-I mimetic peptide increases LCAT activity in mice through increasing HDL concentration. International journal of biological sciences 27 19680471
2007 LCAT can rescue the abnormal phenotype produced by the natural ApoA-I mutations (Leu141Arg)Pisa and (Leu159Arg)FIN. Biochemistry 27 17711302
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1997 Adenovirus-mediated expression of hepatic lipase in LCAT transgenic mice. Journal of lipid research 27 9323591
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1987 The structural gene for lecithin:cholesterol acyl transferase (LCAT) maps to 16q22. Annals of human genetics 27 3674753
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2002 Identification of an IL-6 response element in the human LCAT promoter. Journal of lipid research 15 12032172
2001 Alteration of plasma HDL cholesteryl ester composition with transgenic expression of a point mutation (E149A) of human LCAT. Journal of lipid research 15 11590219
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