Cholesterol and Steroid Metabolism Flashcards
What are the important functions of cholesterol?
1) Component of all cell membranes
2) Precursor of Bile Acids
3) Precursor of steroid hormones and Vitamin D
Describe the structure of cholesterol.
4 carbon ring with a hydrocarbon tail and and OH group at other end.
Where is the site of attachment of fatty acids in cholesterol ester?
OH group on A chain on cholesterol.
What is a cholesterol ester?
Cholesterol molecule with fatty acid attached to OH group end.
What is the main organ cholesterol metabolism takes place?
Liver
cholesterol pool
If cholesterol is completely cut out of the diet, why can high cholesterol levels persist? (in theory)
De Novo Synthesis in liver
What is required for cholesterol synthesis?
Acetyl CoA
NADPH
ATP
What is the rate limiting enzyme in cholesterol synthesis?
HMG CoA reductase
Where is the cell does cholesterol synthesis occur?
Occurs in the cytoplasm with enzymes in cytosol and ER
Too much plasma cholesterol can lead to what?
Atherosclerosis
Too much cholesterol secretion causes formation of what?
Gall Stones
What are the two phases of cholesterol synthesis?
1) synthesis of mevalonic acid (mevalonate)
2) synthesis of cholesterol from mevalonate
How did the Acetyl CoA used in cholesterol synthesis get there?
From citrate, broken down by ATP-citrate lyase.
In the first step of cholesterol synthesis, 2 Acetyl CoA are converted to what? By what enzyme?
Acetoacetyl CoA;
Thiolase
During the second step of cholesterol synthesis, Acetoacetyl CoA is converted to what? By what enzyme?
HMG CoA;
HMG-CoA synthase
HMG CoA is also known as what?
3-hydroxy-3-methylglutaryl CoA
HMG CoA gets converted to what? By what enzyme?
Mevalonate;
HMG CoA Reductase
HMG CoA reductase requires what reducing equivalents?
2 molecules of NADPH
In stage 2 of cholesterol synthesis, Once mevalonate is made, what is formed next?
5-pyrophosphomevalonate
During stage 2 of cholesterol synthesis, what is 5-pyrophosphomevalonate converted into in the 2nd step?
Isopentenyl pyrophosphate (IPP)
Isopentenyl pyrophosphate (IPP), besides beings converted into 3,3-dimethylallyl pyrophosphate (DPP), can also alternately be transformed into what?
Dolichol or ubiquinone
IPP plus DPP undergo condensation to form what?
Geranyl Pyrophosphate (GPP) -10 C
What gets added to Geranyl Pyrophosphate (GPP) to form Farnesyl Pyrophosphate (FPP -15 c)
IPP
2 Farnesyl Pyrophosphate (FPP) molecules are joined to form what?
Squalene (30C)
Farnesyl Pyrophosphate (FPP) (15C) an important intermediate in cholesterol synthesis, can also be a precursor for what?
Dolichol
Ubiquinone
Which two intermediates in cholesterol synthesis can be considered precursors for Dolichol or ubiquinone?
Farnesyl Pyrophosphate (FPP) Isopentenyl Pyrophosphate (IPP)
Is Squalene cyclic or non cyclic?
Non cyclic
Squalene undergoes cyclization to form what?
Lanosterol (30C)