Lecithin:cholesterol acyltransferase in familial HDL deficiency (Tangier disease)

P. Haydn Pritchard, Roger McLeod, Jiri Frohlich, Myung C. Park, B. J. Kudchodkar, Andras G. Lacko

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

These studies were performed to investigate the relationship between the enzyme lecithin:cholesterol acyltransferase and plasma lipoproteins in Tangier disease, a condition characterized by a virtual absence of high-density lipoproteins (HDLs) and an accumulation of cholesteryl esters in peripheral tissues. Apolipoprotein A-I was nearly absent from the patient's plasma (1% of the normal levels were found). However, apolipoprotein A-I purified from the plasma of the Tangier disease patient, was found to activate both purified and the plasma enzyme. At lower apolipoprotein concentrations (up to 25 μg/ml), about twice the amount of Tangier apolipoprotein A-I was required to achieve a certain level of lecithin:cholesterol acyltransferase activity as compared with the activating potential of the normal apolipoprotein. Gel chromatography studies revealed that as in normal plasma, lecithin:cholesterol acyltransferase in Tangier plasma was associated with an HDL-size lipoprotein fraction. However, unlike in normal plasma, this lipoprotein complex (containing lecithin:cholesterol acyltransferase) was not removed from Tangier plasma by immunoaffinity chromatography utilizing immobilized anti-apolipoprotein A-I antibodies. Plasma incubation studies showed that free cholesterol was primarily supplied by LDL in normal plasma, whereas both LDL and VLDL donated the free cholesterol for lecithin:cholesterol acyltransferase reaction in Tangier plasma. The majority of the cholesteryl esters, generated during the incubation experiments, were transferred back to LDL in normal plasma, whereas in Tangier plasma both LDL and VLDL served as cholesteryl ester acceptors. The cholesteryl ester transfer from HDL to lower-density lipoproteins was lower in Tangier plasma as compared to this process in a normal control, suggesting that a minimal cholesteryl ester core may be required for the stability of HDL.

Original languageEnglish
Pages (from-to)227-234
Number of pages8
JournalBiochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
Volume958
Issue number2
DOIs
StatePublished - 4 Feb 1988

Fingerprint

Hypoalphalipoproteinemias
Tangier Disease
Phosphatidylcholine-Sterol O-Acyltransferase
HDL Lipoproteins
Plasmas
Cholesterol Esters
Lipoproteins
Apolipoprotein A-I
Apolipoproteins
Chromatography
Cholesterol

Keywords

  • Cholesteryl ester transfer
  • HDL deficiency
  • Lecithin:cholesterol acyltransferase
  • Lipoprotein
  • Tangier disease

Cite this

Pritchard, P. Haydn ; McLeod, Roger ; Frohlich, Jiri ; Park, Myung C. ; Kudchodkar, B. J. ; Lacko, Andras G. / Lecithin:cholesterol acyltransferase in familial HDL deficiency (Tangier disease). In: Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism. 1988 ; Vol. 958, No. 2. pp. 227-234.
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abstract = "These studies were performed to investigate the relationship between the enzyme lecithin:cholesterol acyltransferase and plasma lipoproteins in Tangier disease, a condition characterized by a virtual absence of high-density lipoproteins (HDLs) and an accumulation of cholesteryl esters in peripheral tissues. Apolipoprotein A-I was nearly absent from the patient's plasma (1{\%} of the normal levels were found). However, apolipoprotein A-I purified from the plasma of the Tangier disease patient, was found to activate both purified and the plasma enzyme. At lower apolipoprotein concentrations (up to 25 μg/ml), about twice the amount of Tangier apolipoprotein A-I was required to achieve a certain level of lecithin:cholesterol acyltransferase activity as compared with the activating potential of the normal apolipoprotein. Gel chromatography studies revealed that as in normal plasma, lecithin:cholesterol acyltransferase in Tangier plasma was associated with an HDL-size lipoprotein fraction. However, unlike in normal plasma, this lipoprotein complex (containing lecithin:cholesterol acyltransferase) was not removed from Tangier plasma by immunoaffinity chromatography utilizing immobilized anti-apolipoprotein A-I antibodies. Plasma incubation studies showed that free cholesterol was primarily supplied by LDL in normal plasma, whereas both LDL and VLDL donated the free cholesterol for lecithin:cholesterol acyltransferase reaction in Tangier plasma. The majority of the cholesteryl esters, generated during the incubation experiments, were transferred back to LDL in normal plasma, whereas in Tangier plasma both LDL and VLDL served as cholesteryl ester acceptors. The cholesteryl ester transfer from HDL to lower-density lipoproteins was lower in Tangier plasma as compared to this process in a normal control, suggesting that a minimal cholesteryl ester core may be required for the stability of HDL.",
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Lecithin:cholesterol acyltransferase in familial HDL deficiency (Tangier disease). / Pritchard, P. Haydn; McLeod, Roger; Frohlich, Jiri; Park, Myung C.; Kudchodkar, B. J.; Lacko, Andras G.

In: Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism, Vol. 958, No. 2, 04.02.1988, p. 227-234.

Research output: Contribution to journalArticle

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T1 - Lecithin:cholesterol acyltransferase in familial HDL deficiency (Tangier disease)

AU - Pritchard, P. Haydn

AU - McLeod, Roger

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AB - These studies were performed to investigate the relationship between the enzyme lecithin:cholesterol acyltransferase and plasma lipoproteins in Tangier disease, a condition characterized by a virtual absence of high-density lipoproteins (HDLs) and an accumulation of cholesteryl esters in peripheral tissues. Apolipoprotein A-I was nearly absent from the patient's plasma (1% of the normal levels were found). However, apolipoprotein A-I purified from the plasma of the Tangier disease patient, was found to activate both purified and the plasma enzyme. At lower apolipoprotein concentrations (up to 25 μg/ml), about twice the amount of Tangier apolipoprotein A-I was required to achieve a certain level of lecithin:cholesterol acyltransferase activity as compared with the activating potential of the normal apolipoprotein. Gel chromatography studies revealed that as in normal plasma, lecithin:cholesterol acyltransferase in Tangier plasma was associated with an HDL-size lipoprotein fraction. However, unlike in normal plasma, this lipoprotein complex (containing lecithin:cholesterol acyltransferase) was not removed from Tangier plasma by immunoaffinity chromatography utilizing immobilized anti-apolipoprotein A-I antibodies. Plasma incubation studies showed that free cholesterol was primarily supplied by LDL in normal plasma, whereas both LDL and VLDL donated the free cholesterol for lecithin:cholesterol acyltransferase reaction in Tangier plasma. The majority of the cholesteryl esters, generated during the incubation experiments, were transferred back to LDL in normal plasma, whereas in Tangier plasma both LDL and VLDL served as cholesteryl ester acceptors. The cholesteryl ester transfer from HDL to lower-density lipoproteins was lower in Tangier plasma as compared to this process in a normal control, suggesting that a minimal cholesteryl ester core may be required for the stability of HDL.

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