Human plasma lecithin-cholesterol acyltransferase. An elucidation of the catalytic mechanism.
Open accessAbstract
Human plasma lecithin-cholesterol acyltransferase (LCAT) transacylates the sn-2 fatty acid of lecithin to cholesterol forming cholesteryl ester and lysolecithin. Measurement of the phospholipase A2 and transacylase activities of the enzyme using proteoliposome substrates and following selective chemical modification of serine, histidine, and cysteine residues of pure homogeneous LCAT indicated the following catalytic mechanism: HS-Cys-E-Ser-OH + lecithin in equilibrium HS-Cys-E-Ser-O-FA + lysolecithin, HS-Cys-E-Ser-O-FA in equilibrium FA-S-Cys-E-Ser-OH, FA-S-Cys-E-Ser-OH + cholesterol-OH in equilibrium HS-Cys-E-Ser-OH + cholesterol-O-FA, where FA denotes fatty acid. Modification of 2 LCAT cysteine residues with 5,5'-dithiobis-(2-nitrobenzoic acid) or treatment with ferricyanide inactivated the transacylase but not the phospholipase A2 activity. Modification of 1 serine residue with phenylmethanesulfonyl fluoride or 1 histidine residue with diethyl pyrocarbonate inhibited cholesteryl ester formation and phospholipase A2 activity. Proteoliposome substrates protected both activities against chemical inactivation. Lecithin alone protected the phospholipase A2 activity against phenylmethanesulfonyl fluoride inactivation but not the transacylase against 5,5'-dithiobis-(2-nitrobenzoic acid) inactivation. Incubation of native LCAT with arachidonyl-CoA or the lecithin-apo-A-I proteoliposome resulted in acylation of three enzyme sites, only one of which was stable to neutral hydroxylamine after denaturation. Fatty acylenzyme oxy- and thioesters were demonstrable in both cases. No transfer of arachidonic acid from iodoacetamide-modified LCAT to cholesterol occurred, indicating that the fatty-acylated serine residue cannot directly esterify cholesterol. Cholesterol arachidonate was formed upon incubation of phenylmethanesulfonyl fluoride-modified LCAT with arachidonyl-CoA.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
LCAT activity was assessed by measuring cholesterol esterification activity using exogenous [3H]cholesterol-labelled HDL proteoliposome discs as the substrate.
“LCAT activity was assessed by measuring cholesterol esterification activity using exogenous [3H]cholesterol-labelled HDL proteoliposome discs as the substrate91.”
From Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses (2016) · cites this paper as [91]
Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 315,771 · see citing works
A SIMPLE METHOD FOR THE ISOLATION AND PURIFICATION OF TOTAL LIPIDES FROM ANIMAL TISSUES
Folch, J., Lees, M., & Stanley, G. H. S. (1957) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)64849-5 · Cited by 65,189 · see citing works
Ellman, G. L. (1959) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(59)90090-6 · Cited by 26,383 · see citing works
THE ATTRACTIONS OF PROTEINS FOR SMALL MOLECULES AND IONS
Scatchard, G. (1949) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1949.tb27297.x · Cited by 19,724 · see citing works
Havel, R. J., Eder, H. A., & Bragdon, J. H. (1955) · Journal of Clinical Investigation · doi:10.1172/jci103182 · Cited by 8,756 · see citing works
Maturation of the head of bacteriophage T4
Laemmli, U. K., & Fãvre, M. (1973) · Journal of Molecular Biology · doi:10.1016/0022-2836(73)90198-8 · Cited by 3,725 · see citing works
The plasma lecithin:cholesterol acyltransferase reaction
Glomset, J. A. (1968) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)43114-1 · Cited by 2,409 · see citing works
Mans, R. J., & Novelli, G. D. (1961) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(61)90009-1 · Cited by 2,051 · see citing works
Serine Proteases: Structure and Mechanism of Catalysis
Kraut, J. (1977) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.46.070177.001555 · Cited by 1,253 · see citing works
[41] Modification of histidyl residues in proteins by diethylpyrocarbonate
Miles, E. W. (1977) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(77)47043-5 · Cited by 807 · see citing works
Gel electrophoresis of proteins: A practical approach
Calvert, R. A. (1982) · Immunology Today · doi:10.1016/0167-5699(92)90190-i · Cited by 788 · see citing works
Determination of Lecithin: Cholesterol Acyltransfer in Human Blood Plasma
Stokke, K. T., & Norum, K. R. (1971) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.3109/00365517109080184 · Cited by 555 · see citing works
Soutar, A. K., Garner, C. W., Baker, H. N., Sparrow, J. T., Jackson, R. L., Gotto, A. M., & Smith, L. C. (1975) · Biochemistry · doi:10.1021/bi00685a003 · Cited by 392 · see citing works
The mechanism of the plasma cholesterol esterification reaction: Plasma fatty acid transferase
Glomset, J. A. (1962) · Biochimica et Biophysica Acta · doi:10.1016/0006-3002(62)90156-7 · Cited by 371 · see citing works
Activation of lecithin: cholesterol acyltransferase by human apolipoprotein A-IV.
Steinmetz, A., & Utermann, G. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)89547-3 · Cited by 345 · see citing works
Chen, C. H., & Albers, J. J. (1982) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38100-1 · Cited by 298 · see citing works
Evidence of an essential histidine residue in thermolysin
Burstein, Y., Walsh, K. A., & Neurath, H. (1974) · Biochemistry · doi:10.1021/bi00698a030 · Cited by 209 · see citing works
Yokoyama, S., Fukushima, D., Kupferberg, J. P., et al. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)79708-5 · Cited by 202 · see citing works
Aron, L., Jones, S., & Fielding, C. J. (1978) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)34488-5 · Cited by 180 · see citing works
Kuksis, A., Myher, J. J., Marai, L., et al. (1975) · Journal of Chromatographic Science · doi:10.1093/chromsci/13.9.423 · Cited by 176 · see citing works
Lecithin : Cholesterol acyltransferase : Effects of substrate composition upon enzyme activity
Fielding, C. J., Shore, V. G., & Fielding, P. E. (1972) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(72)90116-6 · Cited by 147 · see citing works
Radioimmunoassay of Human Apolipoprotein CII
Kashyap, M. L., Srivastava, L., Chen, C. Y., et al. (1977) · Journal of Clinical Investigation · doi:10.1172/jci108753 · Cited by 143 · see citing works
Stoops, J. K., & Wakil, S. J. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)69376-2 · Cited by 137 · see citing works
Chung, J., Abano, D., Fless, G. M., et al. (1979) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)50341-0 · Cited by 123 · see citing works
Albers, J. J. (1978) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.3109/00365517809104899 · Cited by 113 · see citing works
Subbaiah, P. V., Albers, J. J., Chen, C. H., et al. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)70558-4 · Cited by 101 · see citing works
Fatty acid specificity of plasma phosphatidylcholine: cholesterol acyltransferase
Sgoutas, D. S., Leight, M., & King, R. (1972) · Biochemistry · doi:10.1021/bi00752a022 · Cited by 101 · see citing works
Post-heparin serum lecithinase in man and its positional specificity
Vogel, W. C., & Bierman, E. L. (1967) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)38941-0 · Cited by 93 · see citing works
Purification and characterization of human plasma lecithin: cholesterol acyltransferase
Albers, J. J., Cabana, V. G., & Stahl, Y. D. B. (1976) · Biochemistry · doi:10.1021/bi00650a020 · Cited by 84 · see citing works
Waite, M., & Sisson, P. (1973) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)43183-9 · Cited by 74 · see citing works
Zorich, N. L., Jonas, A. M., & Pownall, H. J. (1985) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)39427-9 · Cited by 73 · see citing works
Lecithin: Cholesterol Acyltransferase and Intravascular Cholesterol Transport
Marcel, Y. L. (1982) · Advances in lipid research · doi:10.1016/b978-0-12-024919-0.50009-6 · Cited by 72 · see citing works
Reactivity of the sulfhydryl groups of muscle phosphofructokinase
Kemp, R. G., & Forest, P. B. (1968) · Biochemistry · doi:10.1021/bi00847a022 · Cited by 71 · see citing works
Marcel, Y. L., Vézina, C., Emond, D., et al. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.5.2969 · Cited by 67 · see citing works
Origin and disappearance of plasma lecithin: cholesterol acyltransferase
Osuga, T., & Portman, O. W. (1971) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1971.220.3.735 · Cited by 63 · see citing works
[34] Fluorography for the detection of radioactivity in gels
Bonner, W. M. (1984) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(84)04115-x · Cited by 59 · see citing works
Nichols, A. V., & Gong, E. (1971) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(71)90266-9 · Cited by 58 · see citing works
Microheterogeneity and physical properties of human lecithin-cholesterol acyltransferase.
Doi, Y., & Nishida, T. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)81970-x · Cited by 46 · see citing works
Kitabatake, K., Piran, U., Kamio, Y., et al. (1979) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(79)90181-4 · Cited by 46 · see citing works
Ridgway, N. D., & Dolphin, P. J. (1985) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)34256-5 · Cited by 45 · see citing works
Self-citationJansen, H., & Hülsmann, W. C. (1975) · Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism · doi:10.1016/0005-2760(75)90149-6 · Cited by 43 · see citing works
Utilization of various sterols by lecithin‐cholesterol acyltransferase as acyl acceptors
Piran, U., & Nishida, T. (1979) · Lipids · doi:10.1007/bf02533465 · Cited by 42 · see citing works
Ruch, F. E., & Vagelos, P. R. (1973) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)43198-0 · Cited by 41 · see citing works
[87] Lecithin-cholesterol acyltransferase from human plasma
Doi, Y., & Nishida, T. (1981) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(81)71089-9 · Cited by 41 · see citing works
Stoops, J. K., & Wakil, S. J. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.8.4544 · Cited by 38 · see citing works
Engeser, H., HuBNER, K., STRAUB, J., et al. (1979) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1979.tb19734.x · Cited by 35 · see citing works
Charakterisierung der Acetyltransferase in der Fettsaäresynthetase aus Hefe
Ziegenhorn, J., Niedermeier, R., Nüssler, C., et al. (1972) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1972.tb02097.x · Cited by 32 · see citing works
Jonas, A. M., & McHugh, H. T. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)44461-9 · Cited by 31 · see citing works
Jonas, A., Covinsky, K. E., & Sweeny, S. A. (1985) · Biochemistry · doi:10.1021/bi00335a018 · Cited by 30 · see citing works
Chong, K. S., Jahani, M., Hara, S., et al. (1983) · Canadian Journal of Biochemistry and Cell Biology · doi:10.1139/o83-112 · Cited by 29 · see citing works
Yamazaki, S., Mitsunaga, T., FURUKAWA, Y., et al. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)81971-1 · Cited by 27 · see citing works
Cognet, J. A. H., & Hammes, G. G. (1983) · Biochemistry · doi:10.1021/bi00281a033 · Cited by 27 · see citing works
The role of histidine residues in glutamate dehydrogenase
Tudball, N., Bailey-Wood, R., & Thomas, P. (1972) · Biochemical Journal · doi:10.1042/bj1290419 · Cited by 25 · see citing works
Organic extraction and preparative isoelectric focussing of rat serum apolipoproteins
Dolphin, P. J. (1980) · FEBS Letters · doi:10.1016/0014-5793(80)80956-2 · Cited by 17 · see citing works
Self-citationAmino acid sequence around the reactive cysteine residues in thiolase
Gehring, U., & Harris, J. I. (1968) · FEBS Letters · doi:10.1016/0014-5793(68)80044-4 · Cited by 16 · see citing works
Verdery, R. B. (1981) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(81)90867-6 · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Aho, V., Ollila, H. M., Kronholm, E., Bondia-Pons, I., Soininen, P., Kangas, A. J., Hilvo, M., Seppälä, I., Kettunen, J., Oikonen, M., et al. (2016) · Scientific Reports · doi:10.1038/srep24828 · Cited by 126 · see citing works
Self-citationA lecithin: Retinol acyltransferase activity in human and rat liver
MacDonald, P. N., & Ong, D. E. (1988) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(88)80818-0 · Cited by 108 · see citing works
Hiukka, A., Leinonen, E., Jauhiainen, M., Sundvall, J., Ehnholm, C., Keech, A. C., & Taskinen, M. R. (2007) · Diabetologia · doi:10.1007/s00125-007-0751-8 · Cited by 68 · see citing works
Self-citation
- Authors
- Jauhiainen, M., & Dolphin, P. J.
- Affiliations
- Dalhousie University (CA)
- ORCID
- Jauhiainen, M
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1986-05
- Volume
- 261
- Issue
- 15
- Pages
- 7032-7043
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1480395470
- Cited by
- 169
- References
- 56
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 4 · 2014: 4 · 2013: 3 · 2012: 4
- FWCI
- 17.68
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Lipid Membrane Structure and Behavior
- Keywords
- lecithin:cholesterol acyltransferase, catalytic mechanism, phospholipase A2 activity, cholesteryl ester formation, lysophosphatidylcholine, enzyme inactivation, serine residues, histidine residues, cysteine residues, arachidonic acid, apolipoprotein A-I, proteoliposomes
- MeSH terms
- Acyltransferases, Cysteine, Dithionitrobenzoic Acid, Humans, Kinetics, Phosphatidylcholine-Sterol O-Acyltransferase, Liposomes, Phospholipases A, Protein Binding, Proteolipids, Phospholipases A2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review