Cholestrol metabolism Flashcards
What is cholestrol?
Steroid that: inc/dec membrane stiffness depending on temperature + membrane nature and interactions with cytoskeleton
Where is cholestrol synthesized?
liver
What are the steps in the biosynthesis of cholestrol?
see notes
What is the precursor to all steroid hormones?
- pregnenolone generated from cholestrol by desmolase
- All 5 classes of steroid hormone come from pregnenolone
What molecules are made form cholestrol?
Vitamin D and Bile Salts
How does cholestrol act in cell signalling?
Lipid raft: fluctuating cholestrol and sphingolipid assembly organise signalling by localising key proteins on surface receptor into discreet domains
How is cholestrol transported around the body?
Lipoproteins: overcomes problem of insolubility of lipid in aqueous solutions
What is the structure of lipoproteins?
- Outside: phospholipid monolayer containing cholesterol and apoproteins
- In core: is cholesteryl ester and triacylglycerol
How is cholesteryl ester synthesized?
Cholesteryl ester is synthesized in plasma from cholestrol and phosphatidylcholin
What enzymes are involved in lipoprotein synthesis?
- lecithin cholestrol acyltransferase (LCAT) making cholesteryl esters more hydrophobic than cholestrol and pack more tightly in lipid core
- acyl CoA cholestrol acyltransferase (ACAT) generates cholestrol from long chain fatty acyl CoA (an intracellular enzyme acting on cholestrol taken in by endocytosis)
What is the role of lipoprotein lipase?
- in capillary endothelial cells lining various tissues (adipose, heart, skeletal muscle)
- hydrolysis of triacylglycerols in chylomicrons
- Apoprotein CII on chylomicron activates lipoprotein lipase
Compare HDL and LDL
see notes
Classify lipoproteins according to density
- Chylomicrons (CM)
- Very low density
- Intermeditate density
- Low density
- High density
Give examples of cholestrol transport dysfunctions
Familial Hypercholestrolaemia: monogneic dominant inheritance
- Heterozygote 2-3x higher cholestrol - Homozygote 5x higher - may have severse atherosclerosis and coronary infarction in adolescence - Controlling FH 1. HMG-CoA reductase inhibitors aka statins - competitive inhibitor 2. Resins/ sequestrants: bind/hide away/isolate bile acid-cholestrol complexes preventing reabsoprtion by intesitng - lowers both HDL and LDL - Different disease classes affect different parts of endocytosis
LDL receptor:
- Patients with severe FH lack functional LDLR - Receive LDL and sent to early endosome then recylced back to plasma membrane then transferred to lysosome to give free cholestrol
Statins are highly effective inhibitors of cholesterol synthesis and function by inhibiting which enzyme?
3-hydroxy-3 methylglutaryl-CoA reductase
The bulk of the body’s cholesterol requirements are met by what?
de novo synthesis of cholesterol from acetyl-CoA
