Biochem Flashcards
Where are chylomicrons synthesized?
Intestinal epithelial cells.
Function of Lipoprotein Lipase (LPL).
Breaks up lipoproteins in the blood stream by liberating fatty acids from triglycerides. This enzyme is located on vascular endothelium in highest concentration around adipose tissue.
Main structural protein of chylomicrons.
Apo B48
Function of Apo CII and Apo E.
Apo CII: activates LPL
Apo E: binds receptors on hepatocytes (LRP) so chylomicron remnants and IDL (VLDL remnant) can be reabsorbed by the liver.
Where do chylomicrons obtain Apo CII and Apo E?
From interaction with HDL.
Structural protein of VLDL.
Apo B100
Where does VLDL obtain Apo CII and Apo E?
From HDL
Why does the liver want to reabsorb chylomicron remnants and IDL?
Chylomicron remnant’s cholesterol is recycled for chylomicron production in the small intestines or bile salt production.
IDL can be used to synthesize LDL
Which LDL protein binds the LDL receptor on endothelial cells to allow the LDL to migrate across the endothelium and deliver cholesterol to tissues?
Apo B100
How is the LDL receptor involved in formation of atherosclerosis?
Both endothelial cells AND cells in tissues adjacent to the endothelial cells have LDL receptors. Once the cells in tissues have enough cholesterol they will down-regulate LDL receptors. The endothelial cells will NOT down-regulate the LDL receptors. The LDLs then get “stuck” inside the endothelial cells or in the interstitial space where they can accumulate and lead to plaque formation.
Main structural protein of HDL.
Apo A-1
Location and function of LCAT.
Located in HDL
Enzyme that esterifies cholesterol within the HDL, making it more hydrophilic (so it can’t cross the HDL membrane and into the blood stream). This “traps” the cholesterol in the HDL molecule.
Major way the body eliminates excess cholesterol.
Bile salt production and loss in feces
What is the Friedewald Equation? Why is it used?
Used to predict LDL levels in blood.
Total Cholesterol - HDL - 1/5(triglycerides) = LDL
What is the rate limiting step and major enzymes (2) for cholesterol synthesis?
Acetyl CoA —> mevalonate
HMG-CoA synthase
HMG-CoA reductase (target of statins)
Name and explain 3 ways cholesterol production is regulated by the body.
- Cholesterol binds a membrane protein SCAP which inhibits another membrane protein SREBP from releasing a transcription factor that goes to the nucleus to make the enzyme.
- Presence of sterols (steroid alcohols: cholesterol is a sterol) increases degradation of the HMG-CoA reductase enzyme
- Phosphorylation of HMG-CoA reductase inactivates it. Glucagon and AMP are low energy molecules that activate kinases which phosphorylate the enzyme. Insulin is a high energy molecule that activates phosphatases to re-activate the enzyme so more cholesterol can be made.
What is the first step in atherogenesis?
Some kind of injury to the endothelial lining.
After injury to the endothelium, describe the process of atherogenesis.
- Inflammatory mediators are released by injured endothelium. WBCs migrate to the area.
- LDL migrates into the injury and is modified (oxidized) by ROS released by WBCs.
- WBCs are then attracted to the mLDL molecules and will migrate into the injury to phagocytize the mLDL.
- The mass of foam cells weaken and break the elastic lamina separating the endothelium from the muscle cells allowing them the migrate inward.
- The inward migrating muscle cells have altered gene expression due to loss of uniformity and irregular location and start to calcify. This forms the plaque which may eventually rupture creating an embolus.
Why is atherosclerosis very common in diabetics?
Just like the WBCs oxidize LDL to modify it, glucose can modify LDL by glycation.
What 3 nutrient deficiencies are associated with atherogenesis?
Folate, B6 and B12
How do: C-reactive protein (CRP) Interleukin-6 (IL-6) Serum amyloid A (SAA) Lipoprotein-a (LP-a)
contribute to atherogenesis?
CRP: increases inflammatory response
IL-6: encourages hepatic production and release of CRP
SAA: recruits immune cells
LP-a: competes with plasminogen
Describe the Frederickson Hyperlipidemia Classification: Class I
High chylomicrons and triglycerides due to defective or deficient LPL or Apo CII
Describe the Frederickson Hyperlipidemia Classification: Class IIa
High LDL due to defect in the LDL receptor
Describe the Frederickson Hyperlipidemia Classification: Class IIb
High LDL, VLDL, TGs due to defect in the internalization of the LDL receptor
Describe the Frederickson Hyperlipidemia Classification: Class III
High IDL due to Apo E defect or decreased LDL production.
Describe the Frederickson Hyperlipidemia Classification: Class IV
High VLDL and TGs due to multiple factors
Describe the Frederickson Hyperlipidemia Classification: Class V
High VLDL, chylomicrons, and TGs due to multiple factors.
Which Frederickson classes present with Xanthomas?
Class I and V. Due to accumulation of lipids under the skin.
Name two mechanisms of statins to decreases cholesterol in the serum.
- Inhibits HMG-CoA reductase (major)
2. Increases LDL receptors on liver (minor)
Function of Ezetimibe
Reduces absorption of cholesterol in the GI tract. Often combined with statins for therapy.
Function of Bile Acid Sequestrants
Decrease bile acid reabsorption in the ileum. They bind to the bile salts and form a complex that the ileal receptors don’t recognize.
Function of Niacin
Raises HDL levels
Function of Fibrates.
Raises HDL levels
