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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1975 Aug;72(8):2925–2929. doi: 10.1073/pnas.72.8.2925

Receptor-dependent hydrolysis of cholesteryl esters contained in plasma low density lipoprotein.

M S Brown, S E Dana, J L Goldstein
PMCID: PMC432891  PMID: 241998

Abstract

Selective radioactive labeling of the cholesteryl esters contained within human plasma low density lipoprotein has allowed the study of the metabolism of these molecules in monolayers and extracts of cultured human fibroblasts. In monolayers of normal cells, binding of low density lipoprotein to its cell surface receptor was followed by rapid hydrolysis of the [3H]cholesteryl linoleate contained within the lipoprotein and accumulation of the liberated [3H]cholesterol within the cell. The stoichiometry of the degradative process suggested that the protein and cholesteryl ester components of the lipoprotein were hydrolyzed in parallel. Incubation of intact fibroblasts with chloroquine, a known inhibitor of lysosomal degradative processes, inhibited the hydrolysis of the lipoprotein-bound cholesteryl esters. Fibroblasts from subjects with the homozygous form of familial hypercholesterolemia, which lack functional low density lipoprotein receptors and thus are unable to take up this lipoprotein when it is present in the culture medium at low concentrations, were therefore unable to hydrolyze the lipoprotein-bound [3H]cholesteryl linoleate. However, cell-free extracts from these mutant cells were capable of hydrolyzing the lipoprotein-bound [3H]cholesteryl linoleate at the same rapid rate as normal cells when incubated at acid pH. These data illustrate the essential role of the low density lipoprotein receptor and of lysosomal acid hydrolases in the metabolic utilization of low density lipoproteins by cultured human fibroblasts.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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