Cholesterol And Bile Acids Metabolism Flashcards
Explain the structure of cholesterol and what itnisna precursor of and where it is present
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
How is cholesterol stored in the liver. How does it exit the liver
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
Where does cholesterol synthesis take place and what is it’s major step
It takes place in the cytosol, and it needs the formation of isoprene units from acetyl-coA
Cholesterol synthesis is regulated by?
HMG-coA reductase
What is the target for cholesterol lowering drugs
HMG-COA reductase
What are the 6 main steps of cholesterol synthesis
Generation of isoprene units Isomerization Condensation Oxidation Cyclization Oxidation/methyl transferase
Explain the steps of keto genesis
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
What is the rate limiting step of cholesterol synthesis and what are it’s inhibitors and activators
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
Mevalonate is converted to ?
Phosphomevalonate, by mevalonate-5 phosphotranferase. This requires ATP
Phosphomevalonate is turned into
5-pyrophosphomevalonate, by phosphomevalonate kinase. And the use of ATP
5-pyrophosphomevalonate is turned into
Isopentenyl-pyrophosphate, this is done by pyrophosphomevalonate decarboxylase . And the use of ATP and the release of CO2
Isopentenyl pyrophosphate is turned into
Dimethylallyl pyrophosphate by the enzyme isopentenyl pyrophosphate isomerse
How is geranyl pyrophosphate formed ?
By the combination of a dimethylallyl pyrophosphate and a isopentenyl pyrophosphate (by the enzyme prenyltransferase)
How is farnesyl pyrophosphate formed (15c)
By the combination of a geranyl pyrophosphate with an isopentenyl pyrophosphate with the enzyme prenyltransferase.
How is squalene formed
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
Squalene is turned into 2,3- oxidosqualene (by squalene epoxidase/ squalene monooxygase) and then into?
Protosterol and lanosterol
Where does the reaction of lanosterol into cholesterol occur and how
In the cytosol of the ER, through 19 rxns. It requires O2 and NADPH
What are the 3 things cholesterol can turn into?
Steroid hormones
Cholesteryl ester
Bile Acids (taurocholic acid)
Read slide 22, 24
Picture
Where is colic acid formed?
From cholesterol in the liver. Colic acid by the action of taurine and glycine can become taurocholic acid and glycocholic acid
What is the enterohepatic circle
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
How is HMG-COA reductase controlled?
- 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
Explain SERBP
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.
What is the Function of lovostatin
It indirectly stimulates the synthesis if the LDL- receptor, thus causing increased cholesterol uptake from the blood
What is the role of HDL and LDL
Idk Google it
