56 - Cholesterol Synthesis and Lipoprotein Transport Flashcards
Chemical type of cholesterol
Sterol (modified steroid)
Function of cholesterol in cell membranes
Required for membrane permeability and fluidity
What is cholesterol an important component of?
1)
2)
3)
1) Bile acids
2) Steroid hormones
3) Vitamin D
Is a precursor to these
Critical intermediates in cholesterol synthesis pathway
1)
2)
3)
1) HMG-CoA (hydroxymethylglutaryl)
2) Isoprene
3) Squalene
Function of lipoproteins
Carry cholesterol in the blood
Statin mechanism
HMG-CoA reductase inhibitors
Above what level of total blood cholesterol does risk of heart disease significantly increase?
5mM
Is cholesterol found in plants?
No.
Fates of cholesterol synthesised in the liver 1) 2) 3) 4)
1) Transport (esterified, assembled into VLDL)
2) Bile acid synthesis (stored in gall bladder, used to emulsify dietary fats)
3) Vitamin D, steroid hormone synthesis (in gonads, adrenal glands, skin)
4) Membranes (10-50% of membrane lipid)
What does cholesterol do in a cell membrane?
1)
2)
3)
1) Provides adjustment to mammalian membrane fluidity at 37 degrees.
2) Rigid cholesterol ring fits in between unsaturated fatty acyl chains, makes membrane less fluid.
3) Membrane rafts have higher concentrations of cholesterol, glycolipids, sphingolipids.
Steps of cholesterol synthesis 1) 2) 3) 4) 5) 6) 7)
1) Acetyl-CoA generated in mitochondria
2) Acetyl-CoA converted to HMG-CoA
3) HMG-CoA converted to mevalonic acid by HMG-CoA reductase
4) Mevalonic acid converted to activated isoprene
5) Activated isoprene converted to squalene
6) Squalene converted to cholesterol
7) Cholesterol negatively feeds back on HMG-CoA reductase.
Effect of esterifying cholesterol
Makes it more hydrophobic. Easier to incorporate into lipoprotein structures
What is activated isoprene?
An intermediate in cholesterol synthesis.
Made from mevalonic acid.
Converted to squalene
Derivatives of activated isoprene
1)
2)
1) Carotenoids
2) Quinone electron carriers (EG: ubiquinone in e- transport chain)
Why is cholesterol transported in lipoproteins?
1)
2)
1) Hydrophobic.
2) Would alter properties of membranes and cause problems if delivered to wrong site