Lecture 21: Lipoproteins

Question 1

Triglyceride formation

Answer 1

• Triglycerides are made starting with phosphatidate
• Phosphate is first removed by a phosphatase producing diacylglycerol
• Diacylglycerol acyltransferase adds 3rd fatty acyl tail to make triacylglyceride
• Elevated insulin promotes activation of all enzymes involved(ACC, FAS, and acyltransferases)
• TAGs produced in liver can be released into blood stream as lipoproteins

Question 2

Lipoproteins

Answer 2

• Lipoproteins are transport molecules for hydrophobic TAGs and cholesterol esters throughout the body
• Thin monolayer of phospholipids and cholesterol
• Polar portions of molecules face aqueous exterior, while hydrophobic ones face hydrophobic interior
• Apoproteins are on surface of lipoproteins and are oriented with hydrophilic side chain outwards and hydrophobic side chains inwards

Question 3

Cholesterol Metabolism

Answer 3

• Cholesterol is crucial for membranes and is metabolized to produce hormones and vitamin D3
• Cholesterol is made from acetyl-coA in cytoplasm of liver cells using carbons from fat/protein/carbohydrate catabolism
• Cholesterol can be modified to a hydrophobic acyl-carrying molecule called a cholesterol ester by acyltransferases
• Production of cholesterol requires NADPH and ATP and is regulated by inhibiting an enzyme called HMG-CoA reductase

Question 4

How does exercise lead to inhibition of HMG-CoA reductase

Answer 4

• Epinephrine released -> activate PKA -> phosphorylate HMG-CoA reductase -> no cholesterol synthesis

Question 5

Lipid Transport via Lipoproteins

Answer 5

• Lipoproteins are made in the liver or intestine
• As they travel through the body, fatty acids and cholesterol are transferred to tissues to produce energy, build membranes, or produce other molecules
• Whatever doesn’t get used returns to liver as lipoprotein remnants for recycling. Additional cholesterol and TAGs are synthesized for the production of new lipoproteins
• Excess synthesis of fats, defects in the receptors that recycle lipoproteins, or problems with the activity of HMG-CoA Reductase can disrupt the balance of lipid metabolism and lead to high cholesterol and cardiovascular disease

Question 6

Lipo-proteins

Answer 6

• Different lipoproteins can be differentiated by their individual components(apoproteins, % TAGs, % cholesterol)
• Chylomicrons are made in the small intestine from the diet and are the largest and contain an apoprotein known as apoprotein 48
• Very Low Density Lipoprotein(VLDL) is made by liver and contains the ApoB100 protein
• Lipoprotein lipase attacks VLDL to hydrolyze TAGs and produce Intermediate Density Lipoprotein(IDL) and then Low Density Lipoprotein(LDL)
• High Density Lipoprotein(HDL) is good cholesterol that picks up cholesterol and transports them back to liver for breakdown and recycling

Question 7

Lipoprotein Metabolism in Circulation

Answer 7

• Apoproteins help with targeting and binding to cells and other proteins via non-covalent interactions
• Membrane-bound enzymes help release free fatty acids for cellular use

Question 8

Lipoprotein Classification

Answer 8

• HDL is known as good cholesterol: travels through the body and picks up cholesterol esters using a lecithin cholesterol acyl transferase enzyme; returns remaining cholesterol to liver for processing and breakdown

Question 9

Cholesterol and Cardiovascular Disease

Answer 9

• Cholesterol is found in the diet but is also synthesized in the liver
• The liver is responsible for monitoring cholesterol levels and for lipoprotein recycling and the synthesis of new cholesterol
• Increased cholesterol intake, synthesis in liver, or decreased lipid turnover and use can lead to cardiovascular disease
• Oxidized LDL particles have been found to be principal components in arterial plaques resulting in heart attack or stroke
• Macrophages can’t break down oxidized LDL

Question 10

Improving cardiovascular health

Answer 10

• Exercise and proper diet can help increase HDL and lower LDL levels
• Proper diet includes monitoring fat intake(decrease trans and saturated fat) but also caloric intake
• Decrease stress to lower blood pressure and prevent arterial damage where oxidized LDL accumulates

Question 11

Omega-3 fatty acids

Answer 11

• Omega 3 fatty acid intake have been associated with:
  
  • Reduced VLDL synthesis
  • Reduced availability of FA chains for TAG synthesis
  • Increased phospholipid synthesis
  • Increased beta-oxidation
  • Reduced hepatic ACC and FAS enzyme activity