Cholesterol And Bile Acids Metabolism

Question 1

Explain the structure of cholesterol and what itnisna precursor of and where it is present

Answer 1

It has 4 non aromatic rings, one carbon double bond, one side chain, one hydroxyl group.
It is a precursor of steroid hormones and bile acids.
It is present in the plasma membrane of animal cells

Question 2

How is cholesterol stored in the liver. How does it exit the liver

Answer 2

Stored: from the diet, by de novo synthesis, and cholesterol synthesized in extrahepatic cells.
Release: VLDL , free cholesterol in bile, and conversion to bile acids and salts

Question 3

Where does cholesterol synthesis take place and what is it’s major step

Answer 3

It takes place in the cytosol, and it needs the formation of isoprene units from acetyl-coA

Question 4

Cholesterol synthesis is regulated by?

Answer 4

HMG-coA reductase

Question 5

What is the target for cholesterol lowering drugs

Answer 5

HMG-COA reductase

Question 6

What are the 6 main steps of cholesterol synthesis

Answer 6

Generation of isoprene units 
Isomerization
Condensation
Oxidation
Cyclization
Oxidation/methyl transferase

Question 7

Explain the steps of keto genesis

Answer 7

We start with 2 acetyl groups.
These are removed of a single acetyl group by the enzyme thiolase (acetyl-coa-acetyltransferase).
This formed acetoacetyl- coA
Which is acted on by HMG-coA synthase
And results in HMG-COA

Question 8

What is the rate limiting step of cholesterol synthesis and what are it’s inhibitors and activators

Answer 8

We start with HMG-COA
This is acted on by HMG-coA reductase, and is reduced by 2 NADPH and a Co-A group is released.
Mevalonate is formed

Question 9

Mevalonate is converted to ?

Answer 9

Phosphomevalonate, by mevalonate-5 phosphotranferase. This requires ATP

Question 10

Phosphomevalonate is turned into

Answer 10

5-pyrophosphomevalonate, by phosphomevalonate kinase. And the use of ATP

Question 11

5-pyrophosphomevalonate is turned into

Answer 11

Isopentenyl-pyrophosphate, this is done by pyrophosphomevalonate decarboxylase . And the use of ATP and the release of CO2

Question 12

Isopentenyl pyrophosphate is turned into

Answer 12

Dimethylallyl pyrophosphate by the enzyme isopentenyl pyrophosphate isomerse

Question 13

How is geranyl pyrophosphate formed ?

Answer 13

By the combination of a dimethylallyl pyrophosphate and a isopentenyl pyrophosphate (by the enzyme prenyltransferase)

Question 14

How is farnesyl pyrophosphate formed (15c)

Answer 14

By the combination of a geranyl pyrophosphate with an isopentenyl pyrophosphate with the enzyme prenyltransferase.

Question 15

How is squalene formed

Answer 15

By the combination of 2 farnesyl pyrophosphate molecules. Done by the enzyme squalene synthase. And involves the oxidation of 2 NADPH and the removal of 2 P groups

Question 16

Squalene is turned into 2,3- oxidosqualene (by squalene epoxidase/ squalene monooxygase) and then into?

Answer 16

Protosterol and lanosterol

Question 17

Where does the reaction of lanosterol into cholesterol occur and how

Answer 17

In the cytosol of the ER, through 19 rxns. It requires O2 and NADPH

Question 18

What are the 3 things cholesterol can turn into?

Answer 18

Steroid hormones
Cholesteryl ester
Bile Acids (taurocholic acid)

Question 19

Read slide 22, 24

Answer 19

Picture

Question 20

Where is colic acid formed?

Answer 20

From cholesterol in the liver. Colic acid by the action of taurine and glycine can become taurocholic acid and glycocholic acid

Question 21

What is the enterohepatic circle

Answer 21

Bile salts leave the liver and reach the duodenum and ilium where they turn into bile acids, then they return to the liver on the portal vein and are again turned into bile salts

Question 22

How is HMG-COA reductase controlled?

Answer 22

• phosphorylation by AMP-dependant protein kinase inactivates it
• degradation of it , leading to a brief half life of 3hrs
• enzyme synthesis is controlled by gene expression which is controlled by cholesterol levels

Question 23

Explain SERBP

Answer 23

It is a transcription factor that is encouraged by SCAP . However if cholesterol is present then it makes SCAP inhibited, thus inhibiting SERBP which encourages HMG-COA reductase activity.

Question 24

What is the Function of lovostatin

Answer 24

It indirectly stimulates the synthesis if the LDL- receptor, thus causing increased cholesterol uptake from the blood

Question 25

What is the role of HDL and LDL

Answer 25

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