Sandbox Reserved 595: Difference between revisions

lipoproteins. J. Biol. Chem.271:19053–19057.</ref>'.  This region is protease sensitive '<ref>Freiden, Carl and K. Garai. 2012. Structural differences between apoE3 and apoE4 may be useful in developing therapeutic agents for Alzheimer’s disease. PNAS 109(23):8913-8919.</ref>'.   

ApoE exhibits extensive domain interactions.  Hydrogen bonds and salt-bridges act to shield the major LDLR-binding region.  This protein's unique topology regulates its tertiary structure in order to solely permit one conformation upon binding in a two-step manner.  Lipid-free and partially lipidated ApoE are thwarted from prematurely binding to ApoE receptors by the tertiary structure.  Therefore, the optimal receptor-binding affinity of fully lipidated ApoE is guaranteed.  An active conformation for  biding to members of the low-density lipoprotein receptor family is achieved through binding to lipids and HSPGs '<ref>Chen, J et al.  2011.  Topology of human apolipoprotein E3 uniquely regulates its diverse biological functions.  Proc Natl Acad Sci USA 108(36):14813-8.</ref>'.

==Lipid Metabolism==

The protein, apolipoprotein E, has an important role in lipid metabolism; principally, it serves as a carrier protein.  ApoE combines with lipids in the body to form lipoprotein particles '<ref>Genetics Home Reference. 2013. APOE gene. Ghr.hlm.nih.gov/gene/APOE.</ref>' '<ref>Reynolds, Dawn.  Apolipoprotein E.  www.chem.cuteu.edu/chem4400/sjbr/dan971.htm.</ref>'.  These lipoprotein particles have hydrophobic lipids situated at the core and hydrophilic side chains made of amino acids '<ref>Reynolds, Dawn.  Apolipoprotein E. www.chem.cuteu.edu/chem4400/sjbr/dan971.htm.</ref>'.  Specifically, apoE is responsible for packaging cholesterol,other lipids, and fat soluble vitamins and transporting them systemically '<ref>Han X.  2010.  The pathogenic implication of abnormal interaction between apolipoprotein E isoforms, amyloid-beta peptides, and sulfatides in Alzheimer's disease.  Mol Neurobiol 41(2-3): 97-106.</ref>''<ref>Genetics Home Reference. 2013. APOE gene. Ghr.hlm.nih.gov/gene/APOE.</ref>'.   

Synthesis of this protein primarily occurs in the liver; approximately three-fourths of plasma apoE is generated in the liver by hepatic parenchymal cells '<ref>Genetics Home Reference. 2013. APOE gene. Ghr.hlm.nih.gov/gene/APOE.</ref>'.  In this location, apoE is included as a major component of very-low density lipoproteins (VLDL) '<ref>Genetics Home Reference. 2013. APOE gene. Ghr.hlm.nih.gov/gene/APOE.</ref>' '<ref>Reynolds, Dawn.  Apolipoprotein E.  www.chem.cuteu.edu/chem4400/sjbr/dan971.htm.</ref>'.  VLDL serves to remove excess cholesterol from the blood and to carry it to the liver for processing.  Thus, apoE acts as a cholesterol chaperone '<ref>Arold, S. et al.  2012.  Apolipoprotein E level and cholesterol are associated with reduced synaptic amyloid beta in Alzheimer's disease and apoE TR mouse cortex.  Acta Neuropathol 123(1):39-52.</ref>'.  Maintaining optimal levels of cholesterol is crucial for the prevention of disorders that affect the heart and blood levels '<ref>Genetics Home Reference. 2013. APOE gene. Ghr.hlm.nih.gov/gene/APOE.</ref>'.  Triglycerides are also transported to the liver tissue with the aid of VLDL '<ref>Reynolds, Dawn.  Apolipoprotein E.  www.chem.cuteu.edu/chem4400/sjbr/dan971.htm.</ref>'.  ApoE is essential for the normal catabalism of triglyceride-rich lipoprotein constituents '<ref>Arold, S. et al.  2012.  Apolipoprotein E level and cholesterol are associated with reduced synaptic amyloid beta in Alzheimer's disease and apoE TR mouse cortex.  Acta Neuropathol 123(1):39-52.</ref>'.  In the plasma, apoE will associate with most lipoproteins, however, n the central nervous system, it mainly associates with high-density lipoproteins (HDL) '<ref>Han X.  2010.  The pathogenic implication of abnormal interaction between apolipoprotein E isoforms, amyloid-beta peptides, and sulfatides in Alzheimer's disease.  Mol Neurobiol 41(2-3): 97-106.</ref>'.