Low density lipoprotein physiology: Difference between revisions
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==Overview== | ==Overview== | ||
==Physiology== | |||
LDL’s main role is mediating metabolism and transport of [[cholesterol]]. LDL transports [[cholesterol]] and [[triglycerides]] from the [[liver]] to peripheral tissues. LDL transports approximately 70% of circulating [[cholesterol]].<ref name="pmid12813012">{{cite journal| author=Rader DJ, Cohen J, Hobbs HH| title=Monogenic hypercholesterolemia: new insights in pathogenesis and treatment. | journal=J Clin Invest | year= 2003 | volume= 111 | issue= 12 | pages= 1795-803 | pmid=12813012 | doi=10.1172/JCI18925 | pmc=PMC161432 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12813012 }} </ref> It is formed in the circulation from VLDL by the action of [[lipoprotein lipase]] (LPL). | |||
* LDL receptors, located at specific coat pits on plasma membrane of specific target cells mediate the selective uptake of molecules into cells by [[endocytosis]]. The coat pits contain [[clathrin]] protein on the cytoplasmic end of the plasma membrane to promote [[endocytosis]]. LDL receptors are glycoproteins that have negatively charged domains capable of interacting with positively charged arginine and lysine residues of apo B-100. | |||
* Inside the cell, LDL migrates within a vesicle and is targeted to be degraded within the [[lysosome]] that contains hydrolases capable of digesting components of LDL. LDL degradation produces cholesterol, amino acids, glycerol and fatty acids.<ref name="pmid4355366">{{cite journal| author=Goldstein JL, Brown MS| title=Familial hypercholesterolemia: identification of a defect in the regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity associated with overproduction of cholesterol. | journal=Proc Natl Acad Sci U S A | year= 1973 | volume= 70 | issue= 10 | pages= 2804-8 | pmid=4355366 | doi= | pmc=PMC427113 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4355366 }} </ref> | |||
* Not only does LDL transport cholesterol, but also this activity is key to control cholesterol homeostasis.<ref>Murtola T, Vuorela TA, Hyvonen MT et al. Low density lipoprotein: Structure, dynamics, and interactions of apoB-100 with lipids. Soft Matter. 2011;7:8136-8141 | |||
</ref> Cholesterol derived from LDL following degradation within the lysosome contributes to the feedback inhibition of cholesterol synthesis by directly suppressing the rate-limiting step catalyzed by HMG-CoA reductase enzyme.<ref name="pmid4355366">{{cite journal| author=Goldstein JL, Brown MS| title=Familial hypercholesterolemia: identification of a defect in the regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity associated with overproduction of cholesterol. | journal=Proc Natl Acad Sci U S A | year= 1973 | volume= 70 | issue= 10 | pages= 2804-8 | pmid=4355366 | doi= | pmc=PMC427113 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4355366 }} </ref> | |||
* LDL also has the ability to suppress the transcription of LDL receptor genes, preventing accumulation of cholesterol and keeping cholesterol amounts within membranes constant despite varying cholesterol supply and demand.<ref name="pmid212203">{{cite journal| author=Brown MS, Goldstein JL| title=Regulation of the activity of the low density lipoprotein receptor in human fibroblasts. | journal=Cell | year= 1975 | volume= 6 | issue= 3 | pages= 307-16 | pmid=212203 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=212203 }} </ref><ref name="pmid10500120">{{cite journal| author=Brown MS, Goldstein JL| title=A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood. | journal=Proc Natl Acad Sci U S A | year= 1999 | volume= 96 | issue= 20 | pages= 11041-8 | pmid=10500120 | doi= | pmc=PMC34238 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10500120 }} </ref> | |||
==References== | ==References== | ||
Revision as of 17:21, 12 September 2013
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Cafer Zorkun, M.D., Ph.D. [2]; Rim Halaby, M.D. [3]
Overview
Physiology
LDL’s main role is mediating metabolism and transport of cholesterol. LDL transports cholesterol and triglycerides from the liver to peripheral tissues. LDL transports approximately 70% of circulating cholesterol.[1] It is formed in the circulation from VLDL by the action of lipoprotein lipase (LPL).
- LDL receptors, located at specific coat pits on plasma membrane of specific target cells mediate the selective uptake of molecules into cells by endocytosis. The coat pits contain clathrin protein on the cytoplasmic end of the plasma membrane to promote endocytosis. LDL receptors are glycoproteins that have negatively charged domains capable of interacting with positively charged arginine and lysine residues of apo B-100.
- Inside the cell, LDL migrates within a vesicle and is targeted to be degraded within the lysosome that contains hydrolases capable of digesting components of LDL. LDL degradation produces cholesterol, amino acids, glycerol and fatty acids.[2]
- Not only does LDL transport cholesterol, but also this activity is key to control cholesterol homeostasis.[3] Cholesterol derived from LDL following degradation within the lysosome contributes to the feedback inhibition of cholesterol synthesis by directly suppressing the rate-limiting step catalyzed by HMG-CoA reductase enzyme.[2]
- LDL also has the ability to suppress the transcription of LDL receptor genes, preventing accumulation of cholesterol and keeping cholesterol amounts within membranes constant despite varying cholesterol supply and demand.[4][5]
References
- ↑ Rader DJ, Cohen J, Hobbs HH (2003). "Monogenic hypercholesterolemia: new insights in pathogenesis and treatment". J Clin Invest. 111 (12): 1795–803. doi:10.1172/JCI18925. PMC 161432. PMID 12813012.
- ↑ 2.0 2.1 Goldstein JL, Brown MS (1973). "Familial hypercholesterolemia: identification of a defect in the regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity associated with overproduction of cholesterol". Proc Natl Acad Sci U S A. 70 (10): 2804–8. PMC 427113. PMID 4355366.
- ↑ Murtola T, Vuorela TA, Hyvonen MT et al. Low density lipoprotein: Structure, dynamics, and interactions of apoB-100 with lipids. Soft Matter. 2011;7:8136-8141
- ↑ Brown MS, Goldstein JL (1975). "Regulation of the activity of the low density lipoprotein receptor in human fibroblasts". Cell. 6 (3): 307–16. PMID 212203.
- ↑ Brown MS, Goldstein JL (1999). "A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood". Proc Natl Acad Sci U S A. 96 (20): 11041–8. PMC 34238. PMID 10500120.