Cholestrol synthesis Flashcards
Where does cholesterol synthesis occur?
in the cytosol
How many C atoms does cholesterol contain?
27
The carbon source of cholesterol biosynthesis is …..
acetate/acetyl CoA
What is the energy source for cholesterol biosynthesis?
Hydrolysis of ATP or acetyl CoA
The reducing agent in cholesterol biosynthesis is ………….
NADPH
In the absence of ……….. cholesterol synthesis will not occur.
NADPH
Step 1
Thiolase catalyses the condensation of 2 acetyl CoA molecules to form acetoacetyl CoA
Step 2
Cystolic enzyme, HMG CoA synthase adds another acetyl CoA to acetoacetyl CoA to form a 6C molecule, 3-hydroxy-3-methylglutayrl CoA (HMG CoA)
What step is the rate limiting step and why?
Step 3 because it is irreversible
Step 3
- Rate-limiting step
- HMG CoA reductase catalyses the reduction of HMG CoA to mevalonic acid(mevalonate) by NADPH
What is unique about the location and function of HMGR (HMG CoA reductase)?
found in the membrane of the ER but has its functional domain in the cytosol
Step 4
Kinases hydrolyse ATPs to add 2 phosphate groups to mevalonate to from 5-pyrophosphomevalonate
What does the phosphorylation of mevalonate do to it?
makes it very a hydrophilic molecule
Step 5
- Decarboxylation step
- Decarboxylase uses ATP to decarboxylate 5-pyrophosphomevalonate to isopentenyl pyrophosphate(5C, IPP)
Step 6
Isomerase converts IPP to 3,3-dimethylallyl pyrophosphate (DPP)
Step 7
Transferase catalyses the condensation of DPP and IPP to form geranyl pyrophosphate (10C,GPP)
Step 8
Transferase catalyses another condensation reaction of IPP and GPP to form farnesyl pyrophosphate (15C,FPP)
Step 9
Squalene synthase uses NADPH to combine 2 FPPs and removes 4 phosphate groups to form squalene (30C)
Comment on what happens to squalene due to the absence of phosphate groups
it is hydrophobic and does not dissolve in the cytosol hence it needs an intracellular carrier protein to keep it dissolved in the cytosol
Step 10
Squalene monooxygenase with NADPH and oxygen converts squalene to lanosterol, a 30 C cyclic structure
How many steps does cholesterol biosynthesis have?
10
What happens to lanosterol after it has been produced?
it is converted to cholesterol via a multi-step process by 18+ different enzymes
In what 2 forms does cholesterol exist in the plasma and tissues as
- free cholesterol
- cholesteryl ester
What is the storage form of cholesterol?
cholesteryl ester
In plasma, both forms of cholesterol are transported ………………
in lipoproteins
Cholesterol is the precursor of all other ………………… in the body
steroids
Give 4 examples of steroids that are formed from cholesterol
- sex hormones
- bile acids
- vitamin D
- corticosteroids
Cholesterol occurs in food from …………….
animal metabolism
4 examples of animal products that cholesterol can be obtained from
- egg yolk
- meat
- liver
- brain
What do low-density lipoproteins do with cholesterol?
they transport free cholesterol and cholesteryl ester to many tissues
The function of high-density lipoproteins w.r.t cholesterol
they remove free cholesterol and transport them to the liver for elimination unchanged or by conversion to bile acids
What is reverse cholesterol transport?
removal of free cholesterol from tissues by HDLs and transportation to the liver for elimination
W.r.t to pathology, cholesterol is a main constituent of ……..
gallstones
The chief role of cholesterol in pathological processes is
as a factor in the development in atherosclerosis of vital arteries causing coronary, cerebrovascular and peripheral vascular diseases
