Textbook Reading: Voet & Voet, Biochemistry, 3rd Edition, p. 439-449, 910-914, 951-959.
Some recent articles
B. J. Rollins (2001) "Chemokines and atherosclerosis: what Adam Smith has to say about vascular disease," J. Clinical Invest. 108: 1269-1271.
K. K. Buhman, H. C. Chen & R. V. Farese (2001) "The enzymes of neutral lipid synthesis," J. Biol. Chem. 276: 40369-40372.
G. Rudenko, L. Henry, K. Henderson, K. Ichtchenko, M. S. Brown, J. L. Goldstein & J. Deisenhofer (2002) "Structure of the LDL receptor extracellular domain at endosomal pH," Science 298: 2353-2358.
G. Rudenko & J. Deisenhofer (2003) "The low-density lipoprotein receptor: ligands, debates and lore," Current Opinion in Structural Biol. 13: 683-689.
R. G. W. Anderson (2003) "Joe Goldstein and Mike Brown: from cholesterol homeostasis to new paradigms in membrane biology," Trends in Cell Biol. 13: 534-539.
J. Shepherd (2004) "Lipids in health and disease," Biochem. Soc. Trans. 32: 1051-1056.
N. Beglova & S. C. Blacklow (2005) "The LDL receptor: how acid pulls the trigger," Trends in Biochem. Sci. 30:309-316.
H. Jeon & S. C. Blacklow (2005) "Structure and physiologic function of the low-density lipoprotein receptor," Annu. Rev. Biochem. 74: 535-562.
W. Khovidhunkit, M.-S. Kim, R. A. Memon, J. K. Shigenaga, A. H. Moser, K. R. Feingold & C. Grunfeld (2004) "Effects of infection and inflammation on lipid and lipoprotein metabolism: mechanisms and consequences to the host," J. Lipid Res. 45: 1169-1196.
D. M. Hatters, C. A. Peters-Libeu & K. H. Weisgraber (2006) "Apolipoprotein E structure: insights into function," Trends in Biochem. Sci. 31: 445-454.
A. A. Ajees, G. M. Anantharamaiah, V. K. Mishra, M. M. Hussain & H. M. K. Murthy (2006) "Crystal structure of human apolipoprotein A-I: Insights into its protective effect against cardiovascular diseases," PNAS 103: 2126-2131.
Y. V. Bobryshev (2006) "Monocyte recruitment and foam cell formation in atherosclerosis," Micron 37: 208-222.
P. C. Stolt & H. H. Bock (2006) "Modulation of lipoprotein receptor functions by intracellular adaptor proteins," Cell. Signaling 18: 1560-1571.
J. D. Horton, J. C. Cohen & H. H. Hobbs (2007) "Molecular biology of PCSK9: its role in LDL metabolism," Trends in Biochem Sci. 32: 71-77.
O. Hofnagel, B. Luechtenborg, G. Weissen-Plenz & H. Robenek (2007) "Statins and foam cell formation: Impact on LDL oxidation and uptake of oxidized lipoproteins via scavenger receptors," Biochim. Biophys. Acta 1771: 1117-1124.
1. a. Diagram and describe the structure and composition of low density
lipoprotein (LDL). What precursor to LDL is secreted by the liver, and how is it
converted to LDL?
b. What is the role of the LDL receptor? What are the separate functions of the cytosolic and extracellular domains of the transmembrane LDL receptor? What is the role of the b-propeller domain? How is cellular uptake of LDL regulated? Include the roles of SREBP and the protease PCSK9.
c. Explain the basis of the disease familial hypercholesterolemia. How does this genetic defect promote development of atherosclerosis? What are the options for treatment of a patient with familial hypercholesterolemia? Explain.
2.You may be asked to answer one or more of the following relating to lipid digestion & transport:
a. Write out the reaction catalyzed by pancreatic Phospholipase A2, giving names and structures of substrates and products. (It is OK to use abbreviations for phospholipid headgroup and fatty acid hydrocarbon chains.) What is the role in digestion of a reaction product? Cobra and bee venoms contain phospholipase A2. How does this enzyme injure a recipient of the venom?
b. What is the role of the enzyme Lipoprotein Lipase, found on the lumenal surface of blood capillaries? What reaction does it catalyze? What is the significance of this reaction with regard to LDL formation?
c. What is the role of intestinal fatty acid binding protein? Briefly describe its structure, and the nature of the binding site for fatty acid.
d. Briefly describe the structure of the truncated HDL apolipoprotein A-I, lacking residues 1-43? What is the role of proline residues in this structure? Briefly describe the role of HDL.
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