Inhibition of lecithin:Cholesterol acyltransferase following intravenous administration of heparin in man

Harold L. Rutenberg, Andras G. Lacko, Louis A. Soloff

Research output: Contribution to journalArticleResearchpeer-review

19 Citations (Scopus)

Abstract

1. 1. Lecithin:cholesterol acyltransferase (EC 2.3.1.43) is the enzyme responsible for the esterification of free cholesterol in human plasma. A marked decrease in the initial rate of enzyme activity was observed in the sera of subjects who received 5000 units of heparin intravenously 4 h after a 1200 calorie meal. This inhibition occurred coincident in time with a marked elevation of serum free fatty acid concentration. Both of these effects could be observed as early as I min following heparin administration. 2. 2. When heparin was given to subjects in the fasting state, the inhibition of enzyme activity was seen only in subjects whose serum triglyceride levels were sufficiently high to produce free fatty acid concentrations in excess of 1000 μequiv/1. 3. 3. In vitro addition of free fatty acids (in the form of palmitic acid) and lysolecithin to the reaction mix separately and together also resulted in reduced enzyme activity which could in turn be reversed by increasing amounts of serum albumin. The data are consistent with the presence of multiple sites for the binding of free fatty acids and lysolecithin by serum albumin: One site binds up to 2 moles of free fatty acids per mole of albumin. The excess free fatty acids compete with lysolecithin for a second site, the binding capacity of the lysolecithin being approx. I mole of lysolecithin per mole of serum albumin. Thus, lecithin:cholesterol acyltransferase inhibition may be caused by a combination of elevated free fatty acids and unbound lysolecithin, the latter being a product of the lecithin:cholesterol acyltransferase reaction which apparently cannot be removed from the enzyme surface when free fatty acids already occupy lysolecithin binding sites on serum albumin.

Original languageEnglish
Pages (from-to)419-427
Number of pages9
JournalBiochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism
Volume326
Issue number3
DOIs
StatePublished - 20 Dec 1973

Fingerprint

Phosphatidylcholine-Sterol O-Acyltransferase
Lysophosphatidylcholines
Nonesterified Fatty Acids
Intravenous Administration
Heparin
Serum Albumin
Enzyme activity
Enzymes
Binding Sites
Serum
Plasma (human)
Enzyme inhibition
Palmitic Acid
Inhibition (Psychology)
Esterification
Meals
Albumins
Fasting
Triglycerides
Cholesterol

Cite this

@article{0177340567374d9bb9f0f85842173316,
title = "Inhibition of lecithin:Cholesterol acyltransferase following intravenous administration of heparin in man",
abstract = "1. 1. Lecithin:cholesterol acyltransferase (EC 2.3.1.43) is the enzyme responsible for the esterification of free cholesterol in human plasma. A marked decrease in the initial rate of enzyme activity was observed in the sera of subjects who received 5000 units of heparin intravenously 4 h after a 1200 calorie meal. This inhibition occurred coincident in time with a marked elevation of serum free fatty acid concentration. Both of these effects could be observed as early as I min following heparin administration. 2. 2. When heparin was given to subjects in the fasting state, the inhibition of enzyme activity was seen only in subjects whose serum triglyceride levels were sufficiently high to produce free fatty acid concentrations in excess of 1000 μequiv/1. 3. 3. In vitro addition of free fatty acids (in the form of palmitic acid) and lysolecithin to the reaction mix separately and together also resulted in reduced enzyme activity which could in turn be reversed by increasing amounts of serum albumin. The data are consistent with the presence of multiple sites for the binding of free fatty acids and lysolecithin by serum albumin: One site binds up to 2 moles of free fatty acids per mole of albumin. The excess free fatty acids compete with lysolecithin for a second site, the binding capacity of the lysolecithin being approx. I mole of lysolecithin per mole of serum albumin. Thus, lecithin:cholesterol acyltransferase inhibition may be caused by a combination of elevated free fatty acids and unbound lysolecithin, the latter being a product of the lecithin:cholesterol acyltransferase reaction which apparently cannot be removed from the enzyme surface when free fatty acids already occupy lysolecithin binding sites on serum albumin.",
author = "Rutenberg, {Harold L.} and Lacko, {Andras G.} and Soloff, {Louis A.}",
year = "1973",
month = "12",
day = "20",
doi = "10.1016/0005-2760(73)90142-2",
language = "English",
volume = "326",
pages = "419--427",
journal = "Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism",
issn = "0005-2760",
publisher = "Elsevier BV",
number = "3",

}

Inhibition of lecithin:Cholesterol acyltransferase following intravenous administration of heparin in man. / Rutenberg, Harold L.; Lacko, Andras G.; Soloff, Louis A.

In: Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism, Vol. 326, No. 3, 20.12.1973, p. 419-427.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Inhibition of lecithin:Cholesterol acyltransferase following intravenous administration of heparin in man

AU - Rutenberg, Harold L.

AU - Lacko, Andras G.

AU - Soloff, Louis A.

PY - 1973/12/20

Y1 - 1973/12/20

N2 - 1. 1. Lecithin:cholesterol acyltransferase (EC 2.3.1.43) is the enzyme responsible for the esterification of free cholesterol in human plasma. A marked decrease in the initial rate of enzyme activity was observed in the sera of subjects who received 5000 units of heparin intravenously 4 h after a 1200 calorie meal. This inhibition occurred coincident in time with a marked elevation of serum free fatty acid concentration. Both of these effects could be observed as early as I min following heparin administration. 2. 2. When heparin was given to subjects in the fasting state, the inhibition of enzyme activity was seen only in subjects whose serum triglyceride levels were sufficiently high to produce free fatty acid concentrations in excess of 1000 μequiv/1. 3. 3. In vitro addition of free fatty acids (in the form of palmitic acid) and lysolecithin to the reaction mix separately and together also resulted in reduced enzyme activity which could in turn be reversed by increasing amounts of serum albumin. The data are consistent with the presence of multiple sites for the binding of free fatty acids and lysolecithin by serum albumin: One site binds up to 2 moles of free fatty acids per mole of albumin. The excess free fatty acids compete with lysolecithin for a second site, the binding capacity of the lysolecithin being approx. I mole of lysolecithin per mole of serum albumin. Thus, lecithin:cholesterol acyltransferase inhibition may be caused by a combination of elevated free fatty acids and unbound lysolecithin, the latter being a product of the lecithin:cholesterol acyltransferase reaction which apparently cannot be removed from the enzyme surface when free fatty acids already occupy lysolecithin binding sites on serum albumin.

AB - 1. 1. Lecithin:cholesterol acyltransferase (EC 2.3.1.43) is the enzyme responsible for the esterification of free cholesterol in human plasma. A marked decrease in the initial rate of enzyme activity was observed in the sera of subjects who received 5000 units of heparin intravenously 4 h after a 1200 calorie meal. This inhibition occurred coincident in time with a marked elevation of serum free fatty acid concentration. Both of these effects could be observed as early as I min following heparin administration. 2. 2. When heparin was given to subjects in the fasting state, the inhibition of enzyme activity was seen only in subjects whose serum triglyceride levels were sufficiently high to produce free fatty acid concentrations in excess of 1000 μequiv/1. 3. 3. In vitro addition of free fatty acids (in the form of palmitic acid) and lysolecithin to the reaction mix separately and together also resulted in reduced enzyme activity which could in turn be reversed by increasing amounts of serum albumin. The data are consistent with the presence of multiple sites for the binding of free fatty acids and lysolecithin by serum albumin: One site binds up to 2 moles of free fatty acids per mole of albumin. The excess free fatty acids compete with lysolecithin for a second site, the binding capacity of the lysolecithin being approx. I mole of lysolecithin per mole of serum albumin. Thus, lecithin:cholesterol acyltransferase inhibition may be caused by a combination of elevated free fatty acids and unbound lysolecithin, the latter being a product of the lecithin:cholesterol acyltransferase reaction which apparently cannot be removed from the enzyme surface when free fatty acids already occupy lysolecithin binding sites on serum albumin.

UR - http://www.scopus.com/inward/record.url?scp=0015849008&partnerID=8YFLogxK

U2 - 10.1016/0005-2760(73)90142-2

DO - 10.1016/0005-2760(73)90142-2

M3 - Article

VL - 326

SP - 419

EP - 427

JO - Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism

JF - Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism

SN - 0005-2760

IS - 3

ER -