Biosynthesis of Sterols (1)
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- Three enzymes used in making Mevalonate from Activated Isoprenes
-
1) MEVELONATE-5-PHOSPHOTRANSFERASE
2)PHOSPHOMEVALONATE KINASE
3)PYROPHOSPHOMEVALONATE DECARBOXYLASE - The names of the two activated 5C pieces
-
1) Isopentenyl Pyrophosphate
2) Dimethylallyl Pyrophosphate -
Activated Isoprene-> ?
By what enzyme -
Geranyl Pyrophosphate (10C)
Prenyl Transferase -
Geranyl Pyrophosphate -> ?
By what enzyme -
Farnesyl Pyrophosphate
Prenyl Transferase -
Squalene is formed from which cmpd?
by what enzyme -
Farnesyl Pyrophosphate
(head to head condensation)
Squalene Synthase ** uses NADPH -
Squalene -> ?
By what enzyme? -
Squalene 2,3 Epoxide
Squalene Monooxygenase - What does Squalene Monooxygenase use?
-
O2
NADPH -
Squalene Epoxide -> ?
By what enzyme? -
Lanosterol
Oxidosqualene Cyclase - Lanosterol -> Squalene by which enzyme?
- Acetyl-CoA Cholesterol Acyl Transferase (ACAT)
- 3 diseases of cholesterol deficiency (cause developmental malformations)
-
1) X-Linked Chondroplasia Punctata
2) Lathosterolosis
3)Smith-Lemi-Opitz Syndrome - how are embryonic signaling pathways linked to cholesterol biosynthesis?
- hedgehog family genes are post-translationally modified by the attachment of cholesterol
- the transcription factor that turns on HMG CoA Reductase?
- SREBP (Sterol Regulatory Element- Binding Proteins)
- What is SCAP?
- protein that prevents the release of SREBP- keeps it in the ER
- what type of protein is SREBP?
- Integral Membrane Protein )synthesized on RER)
- What is SRE?
- Sterol Regulatory Element- DNA sequence that activateds transcription of HMG-CoA Reductase
- Does Insulin or Glucagon stimultae HMG CoA Reductase?
- Insulin
- Is HMG CoA Reductase active in Phosphorylated or Dephosphorylated form?
- Dephosphorylated form (by Insulin)
- What is glucagon's action on cholesterol synthesis?
- Inhibits
- What can cholesterol itself stimulate?
-
1)Proteolytic cleavage of HMG CoA Reductase
2) ACAT - drug that has two H's
- Compactin
- drug that has two CH3's
- Stimvastatin
- Drug that has one H and one OH
- Pravastatin
- Drug that has one H and one CH3
- Lovastatin
- Pleiotrophic effects of Statins
-
-increase NO levels (eNOS expression)
-block other intermediatees of the biosynthetic pathways -
most common bile acid
(extra COO- and 2 extra OH's) - Cholic Acid
- where are bile acids synthesized?
- in the liver
- function of bile acids
- emulsifying agents that prepare triglycerides for hydrolysis by pancreatic lipases
- What are the cholesterol synthesis enzymes that require NADPH?
-
1)HMG CoA Reductase
2)Squalene Synthase
3)Squalene Monooxygenase - which cholesterol synthesis enzyme uses molecular oxygen?
- Squalene Monooxygenase