Week 12 Objectives

Question 1

Explain the importance of cholesterol as an essential structural component of cell membranes and as a precursor of all other steroids in the body, and indicate its pathologic role in cholesterol gallstone disease and atherosclerosis development.

Answer 1

Cholesterol synthesis is a cytosolic process.
Present in ALL tissues as cholesterol/cholesteryl ester
Used as a substrate for:
-steroid hormones
-sex hormones
-bile acids
-Vitamin D

Transported through lipoproteins

Question 2

Identify the five stages in the biosynthesis of cholesterol from acetyl-CoA.

Answer 2

Starts with acetyl-CoA

Synthesis of mevalonate
*regulatory enzyme: HMG-CoA reductase

End: cholesterol

Question 3

Indicate the role of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) in controlling the rate of cholesterol synthesis and explain the mechanisms by which its activity is regulated.

Answer 3

Regulation of HMG-CoA reductase:
Activated by:
-sterol response element binding protein SREBP) mediated transcription
-Insulin mediated dephosphorylation

Inhibited by:

• insig that binds SREBP + retains it in ER
• elevated sterols/cholesterol (degradation of enzyme)
• AMPkinase mediated phosphorylation
• glucagon

Question 4

Explain that cholesterol balance in cells is tightly regulated and indicate the factors involved in maintaining the correct balance.

Answer 4

LDL receptor activity increases LDL, reduces HMG-CoA
-incr. LDL cholesterol reduces HMG-CoA reductase activity/HMG-CoA

PSK9 and incr. cholesterol regulate LDL receptors.

Statins: class of drugs that inhibit HMG-CoA reductase

Question 5

Explain the role of plasma lipoproteins, including chylomicrons, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL), in the transport of cholesterol between tissues in the plasma.

Answer 5

CETP: cholesterol ester transfer protein

• associated with HDL
• exchanges TAGs from VLDL w/ cholesterol esters from HDL

Question 6

Name the two main primary bile acids found in mammals, outline the pathways by which they are synthesized from cholesterol in the liver.

Answer 6

excess cholesterol is bile acid or unesterified cholesterol

1. cholic acid
2. chenodoexy acid

Question 7

Explain the importance of bile acid synthesis not only in the digestion and absorption of fats but also as a major excretory route for cholesterol.

Answer 7

bile acids reabsorbed in the ileum

secondary bile salts less soluble (excreted mostly)

Cholesterol 7-hydroxylase* regulatory step in BAS

Question 8

Explain what is meant by “enterohepatic circulation” and why it is important.

Answer 8

liver->bile->small intestine->absorption