BIOMAT Database Logo BIOMAT Database Logo

Low density lipoprotein metabolism in cultured fibroblasts from a new group of patients presenting clinically with homozygous familial hypercholesterolemia. 1982

G A Coetzee, and D R van der Westhuyzen, and G M Berger, and H E Henderson, and W Gevers

The metabolism of low density lipoproteins (LDL) was studied in cultured fibroblasts obtained from five local patients diagnosed, on the basis of clinical features and serum cholesterol concentrations, as having the homozygous form of familial hypercholesterolemia. LDL receptor function was assessed by measuring the binding, internalization, and degradation of 125I-labeled LDL, and by measuring the stimulation of cellular acyl-CoA cholesterol acyltransferase (ACAT) activity which followed exposure to LDL. Fibroblasts from two cases (CF and GM) showed receptor activities which were approximately 10% of the values obtained with normal cells, while ACAT stimulation by LDL was very low. These two patients were classified as homozygous for a receptor-defective abnormality. However, fibroblasts from the other three patients (JG, ES, and TT) showed greater than 25% of normal receptor activity, as assessed by 125I-LDL binding and catabolism. ACAT stimulation by LDL in cells from JG and ES was within the range of values shown by cells previously characterized as heterozygous for a receptor-negative mutation. Cells from ES behaved atypically: a low, but nonsaturable, activation by LDL was evident. ACAT stimulation by LDL was normal in cells from TT. Receptor activities of the cells from the available parents, assessed on the basis of LDL binding and degradation or of ACAT stimulation, were not clearly distinguishable from those of normal cells. These results add to the growing evidence of genetic heterogeneity underlying the clinical picture associated with familial hypercholesterolemia in different geographical distributions.

UI MeSH Term Description Entries
D008077 Lipoproteins, LDL A class of lipoproteins of small size (18-25 nm) and light (1.019-1.063 g/ml) particles with a core composed mainly of CHOLESTEROL ESTERS and smaller amounts of TRIGLYCERIDES. The surface monolayer consists mostly of PHOSPHOLIPIDS, a single copy of APOLIPOPROTEIN B-100, and free cholesterol molecules. The main LDL function is to transport cholesterol and cholesterol esters to extrahepatic tissues. Low-Density Lipoprotein,Low-Density Lipoproteins,beta-Lipoprotein,beta-Lipoproteins,LDL(1),LDL(2),LDL-1,LDL-2,LDL1,LDL2,Low-Density Lipoprotein 1,Low-Density Lipoprotein 2,LDL Lipoproteins,Lipoprotein, Low-Density,Lipoproteins, Low-Density,Low Density Lipoprotein,Low Density Lipoprotein 1,Low Density Lipoprotein 2,Low Density Lipoproteins,beta Lipoprotein,beta Lipoproteins
D008297 Male Males
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002648 Child A person 6 to 12 years of age. An individual 2 to 5 years old is CHILD, PRESCHOOL. Children
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children
D002785 Sterol O-Acyltransferase An enzyme that catalyzes the formation of cholesterol esters by the direct transfer of the fatty acid group from a fatty acyl CoA derivative. This enzyme has been found in the adrenal gland, gonads, liver, intestinal mucosa, and aorta of many mammalian species. EC 2.3.1.26. Acyl-CoA-Cholesterol Acyltransferase,Cholesterol Acyltransferase,Cholesterol Esterifying Enzyme,Acyl CoA Cholesterol Acyltransferase,Acyltransferase, Acyl-CoA-Cholesterol,Acyltransferase, Cholesterol,Enzyme, Cholesterol Esterifying,Esterifying Enzyme, Cholesterol,O-Acyltransferase, Sterol,Sterol O Acyltransferase
D005260 Female Females
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D006720 Homozygote An individual in which both alleles at a given locus are identical. Homozygotes

Related Publications

G A Coetzee, and D R van der Westhuyzen, and G M Berger, and H E Henderson, and W Gevers
Low density lipoprotein receptor activity in homozygous familial hypercholesterolemia fibroblasts.
November 1982, The Journal of biological chemistry,
G A Coetzee, and D R van der Westhuyzen, and G M Berger, and H E Henderson, and W Gevers
Low density lipoprotein apheresis in pediatric patients with homozygous familial hypercholesterolemia.
April 2009, Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy,
G A Coetzee, and D R van der Westhuyzen, and G M Berger, and H E Henderson, and W Gevers
Degradation of cationized low density lipoprotein and regulation of cholesterol metabolism in homozygous familial hypercholesterolemia fibroblasts.
September 1976, Proceedings of the National Academy of Sciences of the United States of America,
G A Coetzee, and D R van der Westhuyzen, and G M Berger, and H E Henderson, and W Gevers
Low-density lipoprotein apheresis in homozygous familial hypercholesterolemia.
July 2001, The American journal of cardiology,
G A Coetzee, and D R van der Westhuyzen, and G M Berger, and H E Henderson, and W Gevers
Enhanced degradation of trypsin-treated low density lipoprotein by fibroblasts from a patient with homozygous familial hypercholesterolemia.
April 1978, Biochimica et biophysica acta,
G A Coetzee, and D R van der Westhuyzen, and G M Berger, and H E Henderson, and W Gevers
Analysis of low-density lipoprotein receptor gene mutations in a Chinese patient with clinically homozygous familial hypercholesterolemia.
October 2003, Chinese medical journal,
G A Coetzee, and D R van der Westhuyzen, and G M Berger, and H E Henderson, and W Gevers
Genetics of the low density lipoprotein receptor: I. Low density lipoprotein receptor activity in cultured fibroblasts from subjects with or without familial hypercholesterolemia.
August 1981, Clinical genetics,
G A Coetzee, and D R van der Westhuyzen, and G M Berger, and H E Henderson, and W Gevers
Long-term effect of low-density lipoprotein apheresis in patients with homozygous familial hypercholesterolemia.
August 2003, Therapeutic apheresis and dialysis : official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy,
G A Coetzee, and D R van der Westhuyzen, and G M Berger, and H E Henderson, and W Gevers
Comparison of two low-density lipoprotein apheresis systems in patients with homozygous familial hypercholesterolemia.
August 2016, Journal of clinical apheresis,
G A Coetzee, and D R van der Westhuyzen, and G M Berger, and H E Henderson, and W Gevers
Homozygous familial hypercholesterolemia mutant with a defect in internalization of low density lipoprotein.
August 1981, Proceedings of the National Academy of Sciences of the United States of America,
Copied contents to your clipboard!