Statins Flashcards
List each of the lipoproteins
a. Chylomicrons
b. VLDL’s
c. LDL’s
d. HDL’s
Describe in detail (as covered in class) each of the lipoproteins, including their function.
a. Chylomicrons: transport lipids absorbed from the intestine to adipose, cardiac, and skeletal muscle tissue. (transports exogenous (dietary) products)
b. VLDL’s: (More fat) Very-low-density lipoproteins transport endogenous triglycerides, phospholipids, cholesterol, and cholesteryl esters. (transports endogenous products)
c. LDL’s: (A lot cholesterol) LDL delivers fat molecules to cells. Carry cholesterol from liver to cells. When a cell needs cholesterol, it expresses the LDL receptor
d. HDL’s: (Fewer lipids) remove fats and cholesterol from cells, and transport it back to the liver for excretion or re-utilization. Carry cholesterol from cells to liver
What is the clinical measure of a healthy cholesterol balance in the blood?
a. Mortality is associated with high levels of LDLs or low levels of HDLs
b. HDL/LDL
From a pharmacological point of view, how were statins developed? Fig. CS1.13 will be provided
a. Identified by screening compounds produced by microorganisms
b. Microbes lacking HMGR might produce HMGR inhibitors to inhibit microbes which do have HMGR - chemical warfare
c. Compactin (Mevastatin) isolated from Penicillium citrinum
d. 10,000 x higher affinity for enzyme than substrate
Describe the structural differences between Type I and Type II statins with respect to their functions
a. Type I: General structure of type I statins contains a polar head and a hydrophobic moiety including a decalin ring. Disadvantages of Type I statins: Various side effects, Difficult to synthesise, Large number of asymmetric centres
b. Type II: Synthetic agents, Contain larger hydrophobic moiety with no asymmetric centres, Easier to synthesise, Less hydrophobic statins have fewer side effects. MORE POLAR less side effects
What were the improvements in Statin Type II over Type I drugs?
a. Less hydrophobic, no asymmetric centres
Why were Type II drugs developed?
Side effects thought to be due to inhibition of HMGR in other cells such as muscle cells, less hydrophobic the statin, the less side effects
Please describe in detail exactly how Statin drugs work.
a. A drug that mimics the natural substrate HMG-SCoA and inhibits HMG-CoA reductase, statins block the pathway for synthesizing cholesterol in the liver.
b. Decrease cholesterol results in increased LDL receptor on liver cells, this brings in more LDL which decreases LDL in plasma
Why do patients on Statins need to have regular check ups?
a. Side effects thought to be due to inhibition of HMGR in other cells such as muscle cells
b. Less hydrophobic the statin, lower the side effects. Why?
c. Common side effect is myalgia (muscle pain)
d. Rhabdomyolysis = severe muscle toxicity which can be fatal
What is the role of the hydrophobic residue in the statin drugs?
a.
