Cholesterol Biosynthesis and Sterol Derivatives Flashcards
Describe Cholesterol structure
Hydrophobic with four fused hydrocarbon rings (called the steroid nucleus)
What are sterols?
Sterols are steroids with eight to ten carbon atoms in the side chain at C-17 and a hydroxyl group at C-3.
Cholesterol is the major sterol in animal tissues. Plant sterols are poorly absorbed by humans
What are Cholesteryl esters (CE)?
Most plasma cholesterol is in an esterified form causing it to be even more hydrophobic than free cholesterol. These do not work well in membranes and are only present in low levels in most cells
What do acetate and NADPH do for cholesterol synthesis?
Acetate provides the carbon atoms in cholesterol and NADPH provides the reducing equivalents
How is the pathway for cholesterol synthesis driven? And where does it occur?
Pathway is driven by hydrolysis of the high-energy thioester bond of acetyl CoA and there terminal phosphate bond of ATP.
Synthesis occurs in the cytoplasm with enzymes in both the cytosol and at the membrane of the E.R.
How do you synthesize HMG-CoA?
2 Acetyl CoA –> Acetoacetyl CoA –> HMG-CoA
What does HMG-CoA reductase do? What inhibits it?
HMG-CoA reductase converts HMG-CoA to Mevalonic Acid.
Cholesterol will inhibit it
Describe process of Mevalonic Acid to FPP
See powerpoint and write out
What is squalene?
When two molecules of farnesyl pyrophosphate (FPP) combine and release pyrophosphate and are reduced they form squalene
What causes the conversion of squalene to lanosterol?
The hydroxylation of squalene will trigger the cyclization of the structure to lanosterol
What is Smith-Lemli-Opitz Syndrome (SLOS)?
A common autosomal recessive disorder of cholesterol biosynthesis, caused by a partial deficiency in 7-dehydrocholesterol reductase which is an enzyme that is involved in converting 7-dehydrocholesterol to cholesterol
What is the first precursor to sterol? What is the last precursor to sterol?
Lanosterol is the first precursor
7-dehydrocholesterol is the last precursor sterol en route to cholesterol
What does SREBP2 do? What happens when you have low or high cholesterol?
When SREBP2 binds to SRE it will increase expression of HMG-CoA reductase.
When you have low cholesterol, SREBP2 activity will increase.
When you have high cholesterol, SREBP2 activity is reduced
SREBP2 activation also activates the LDLR gene
What does Dihydrolanosterol or 27 hydroxycholesterol do?
It affects the stability of the HMG-CoA reductase protein and leads to decreased stability (and therefore increased degradation)
Describe when HMG-CoA reductase is phosphorylated and dephosphorylated
ACTIVE: Dephosphorylated
INACTIVE: Phosphorylated
