Lipids & Cholesterol

Question 1

Components of a phospholipid

Answer 1

Question 2

What is the role of phospholipids in the cell membrane?

Answer 2

1. The cell membrane mostly constitutes of phospholipids in a lipid bilayer, with the hydrophilic head directed outward & the hydrophobic tails directed into the cells
2. It contains hydrophobic tails which have one long chain PUFA
3. Produces non-polarity in the tail which prevents tight packing of the FA molecules and contributes to the fluidity of the membrane
4. Cell membrane is hydrophobic in whole because of the long tail (so it acts as a semi permeable membrane)
5. Allows some gases (O2 and CO2) and small nonpolar/ uncharged molecules (urea) to pass through but not large and polar molecules (glucose)
6. Helps to keep the intracellular & extracellular concentration of various molecules somewhat constant

Question 3

What are the functions of cholesterol?

Answer 3

1. Essential structural component of cell membrane & outer layer of plasma lipoprotein
2. Constituent of plasma lipoproteins – LDL and HDL
3. Precursor to steroid hormones such as corticosteroids produced by the adrenal cortex & sex hormones
4. Precursor to bile acids and vitamin D

Question 4

Explain the biochemical basis of using statins to manage hypercholesterolemia

Answer 4

1. Hypercholesterolemia is the presence of high plasma cholesterol levels with normal plasma TAG due to rise in cholesterol and LDL
2. Cholesterol is synthesized in the cytoplasm by acetyl coA and acetoacetyl coA which is converted to HMG which is converted to Mevalonate (rate limiting step of cholesterol synthesis)
3. Statins are competitive inhibitors of HMG coA reductase
4. Causes the reduction of cholesterol synthesis and thereby activates sterol regulatory element binding protein 2 (SREBP2), which is a transcription factor that regulates the expression of the gene encoding the LDL receptors
5. } Increases the LDL levels and decreases the cholesterol levels in blood and helps to reduce hypercholesterolemia

Question 5

Explain the biochemical basis of how cholesterol synthesis is regulated

Answer 5

1. Cholesterol is an important molecule for normal body function, but excess can lead to diseases such as atherosclerosis
2. Must be regulated so that the biosynthesis inside the body is there only to compensate for dietary deficiency
3. Cholesterol synthesis is regulated by the following rate limiting irreversible step:
4. HMG coA reductase is regulated by the allosteric activation or inhibition of the enzyme itself, or the suppression of HMG coA reductase transcription gene
5. Cholesterol inhibits HMG coA reductase by end product inhibition, as well as suppresses the gene
6. Plasma cholesterol transporting proteins, such as HDL, LDL & chylomicrons indicates sufficient dietary intake of cholesterol compounds, so they inhibit gene expression
7. Bile acids also inhibit genes because excess bile acids signal excess production or intake of cholesterol
8. Phosphorylation of the enzyme inactivates it, while dephosphorylation activates it (covalent modification)
9. Insulin & Thyroxine activate cholesterol synthesis (by dephosphorylation)
10. Glucagon, Epinephrine & Cortisol inhibit it (by cAMP regulated kinase mediated phosphorylation)
11. Statin drugs act as reversible competitive inhibitors of HMG coA reductase, thus inhibiting the enzyme