Metabolism Lecture 7 - Cholesterol Breakdown/Synthesis

Question 1

What are two ways that cholesterol is obtained?

Where is it packaged and into what?

Answer 1

1. Diet (animal sources) –> package TAGS into chylomicrons in intestinal cells
2. Synthesized in the liver (in vivo)
   - packaged into VLDL along with TAG

Question 2

What is cholesterol a component of?

What is a precursor to? (2)

Answer 2

1. Cell membranes (also stored as a cholesterol ester)
2. • Steroid Hormones (endocrine) –> VITAMIN D
   • Bile acids (made in the liver)

Question 3

What is mevalonate formed from?

What is the rate limiting enzyme?

Answer 3

HMG Co A to Melvonate
- initially from acetoacetyl Co A + Acetyl Co A

rate limiting: HMG - Co A REDUCTASE

Question 4

What regulates the activity of HMG Co - A REDUCTASE? (4)

Answer 4

1. Melvonate - negatively
2. Cholesterol - Neg
3. AMP - negatively regulates
4. Sterols - NEGATIVELY

Question 5

How do the following regulate HMG - CO A REDUCTASE (in liver)

1. Cholesterol
2. AMP
3. Mevalonate
4. Insulin
5. Glucagon
6. Statin Drugs

Answer 5

1. Cholesterol - INHIBITS
2. AMP - INHIBITS
3. Mevalonate - INHIBITS
4. Insulin - STIMULATE
5. Glucagon - INHIBIT
6. Statin Drugs - inhibit cholesterol synthesis!!
   - needs LDL receptors in the Liver in order to be functional

Question 6

Describe what happens after Malonate is formed in order to get cholesterol(4).

Answer 6

1. form Farnesyl Pyrophosphate
2. Form Squalene from 2 molecules of Farnesyl pyrophosphate
3. Convert Squalene 2,3-epoxide to Lanosterol
4. Conversion of LANOSTEROL (C30) to CHOLESTEROL

Question 7

What are 4 ways to regulate HMG - Co A Reductase Activity (besides product concentration)

Answer 7

1. mRNA production
   - ex sterols bind to SRE (steroid reg. elements) and inhibit mRNA production
   - decreased enzyme synthesis & decreased cholesterol
2. mRNA TRANSLATION
   - inhibited by non sterol metabolites from mevalonate
3. Enzyme degradation
   - high levels of cholesterol & mevalonate lead to degradation of HMG CO A Reductase
4. Phosphorylation
   - phosphorylated and inhibited by AMP-Activated Protein Kinase
   - cholesterol synthesis ceases when ATP is low!

Question 8

What is the rate limiting enzyme in BILE ACID/SALT formation from cholesterol?

Answer 8

7alpha - hydroxylase

Question 9

How does cholesterol excess affect the following:

1. HMG - Co A Reductase
2. ACAT
3. 7-alpha hydroxylase

Deprivation?

Answer 9

1. HMG - Co A Reductase - DECREASED cholesterol synthesis
2. ACAT - INCREASES cholesterol storage as chol. esters
3. 7-alpha hydroxylase - INCREASED Bilace acid formation from cholesterol

OPPOSITE FOR DEPRIVATION

Question 10

What is the function of HSTL?

HMG Co A SYNTHASE? (where is it present)

Answer 10

1. Converts TAGs into Fatty Acyl Co A’s
2. Converts Acetyl CO A into KETONE BODIES
   - present only in mitochondria

Question 11

In the liver, cholesterol and TAG ispackaged into _____.

Answer 11

VLDL

Very Low Density Lipoproteins