Lipid Cholesterol Metabolism

Question 1

Cholesterol is synthesized from what? Where?
Vehicles of Cholesterol Transport?
Name other types of organs that do Cholesterol synthesis?
What is needed for Cholesterol Synthesis (3)?
Acetyl-CoA is always produced in the?

Answer 1

Acetyl CoA; Liver (cytosol)
Chylomicron, VLDL Remnants (high cholesterol)
Adrenal Cortex, Sex organs
ATP, NADPH (HMS) Acetyl-CoA
Mitochondria

Question 2

4 Functions of Cholesterol

Answer 2

Component of Membrane

Steroid/Bile Precursors

Question 3

What is the rate limiting step of Cholesterol synthesis?
Reactants, Enzyme, Product

*this enzyme is heavily regulated

Answer 3

HMG-CoA + NADPH –> HMG Reductase –>

Mevalonate (C6)

Question 4

Cholesterol Synthesis past Mevalonate (C6)? What did we need to know?

LOTS OF ATPPP

Answer 4

Mevalonate (C6) is decarboxylated –> C5 –> 6 of C5 merge forming Lanosterol (C30) –> modified (remove methyls and double bonds) –> Product = C27

Question 5

What happens to intercellular Cholesterol (2)

How do we get rid of cholesterol? ***

Answer 5

Bile Salts/Acids **
Hormones

or can be esterified, and stored in lipid droplet temporarily)

Question 6

How do liver cells react to over storage of Cholesterol (2): Im taking Cholesterol induced.

Answer 6

Down regulate LDL receptor synthesis (cholesterol accumulation causes –> change to cholesterol ester.
Inhibits LDL Receptor

Down regulate Cholesterol synthesis, through enzyme HMG -CoA reductase: Cholesterol accumulation causes enzyme to be phosphorylated (like glucagon does)

Question 7

Name (2) ways by which HMG-CoA Reductase enzyme activity is reduced in the presence of Cholesterol? (details on #2)

Answer 7

1) Cholesterol Feedback Inhibition
2) Cholesterol Affects transcription on enzyme.
* **interferes w/activation, TF binding, and mRNA stability

Question 8

Name and explain the two regulatory hormones?

Answer 8

Insulin (+) Gene expression and activity of enzyme

Glucagon (-) Gene expression and activity of enzyme

Question 9

Drugs to Reduce Cholesterol Synthesis? (2)

Answer 9

Statins (Lipitor): Competitively binds to HMG-CoA Reductase –> less cholesterol syntesis

Bile secretion enhancers

Question 10

Where in the liver cells are bile acids made?
Primary Bile Acids (C-Acids) vs Secondary (L/D - Acids)
Are both primary and secondary acids reabsorbed?
Where are secondary bile acids and salts absorbed?
Bile Acid vs Salts

Answer 10

Peroxisomes
Secondary - modified by intestinal bacteria
Yes
colon (Bacteria)
Bile acids have coo- group, in salts coo- is esterified

Question 11

Give the reaction, enzyme (rate limiting) and allosteric inhibitor that is related to bile synthesis from cholesterol

Answer 11

Cholesterol –> Cholic Acid (bile)
Cholesterol 7 - alpha- hydroxylase
Cholic acid buildup down regulates enzyme.

Question 12

Bile Acids help… (2)

Answer 12

ADEK absorption, activate pancreatic lipases