Cholesterol Flashcards
How many carbons are in cholesterol?
26
In whose cells, is cholesterol not needed?
in plants and yeast
What do plants and yeast have, in ‘replacement’ for cholesterol?
sterols
Is cholesterol an energy source?
No
Why are there barely changes to its structure?
has extra double bond due to enzyme gene mutation (can be pathological)
What is the gene mutation for the extra double bond in cholesterol called?
Smith-Lemli-Opitx syndrome
How much of cholesterol comes from diet?
20-30%
Which organ in the body is the most cholesterol rich?
brain
Why is the brain rich in cholesterol?
- makes and recycles all its own cholesterol
- BBB cant take up circulating (dietary) cholesterol
Examples of cholesterol in the body
- steroid hormones (progesterone)
- bile acids (cholic acid)
- covalent addition to proteins (hedgehog)
What are cholesteryl esters for?
cholesterol storage
Where is cellular cholesterol from?
- via endogenous synthesis
- in endoplasmic reticulum
- from acetyl-coA
- regulated at HMG-CoA reductase step
- delivery from circulation in cholesteryl ester form, in complex with LDL (then internalised and released)
How much cholesterol is synthesised in the liver?
1g/day
What are the main steps in cholesterol synthesis?
- 3-acetyl-coA
- HMG-CoA
- Mevalonate
- Isopentyl Pyrophosphate
- Squalene
- Cholesterol
How many pathways are there from squalene to cholesterol and what are they called?
Two.
- Bloch pathway
- Kandutsh-Russell pathway
Which pathway, bloch or kandutsh is more dominant?
Bloch pathway
How is cellular cholesterol levels regulated?
- synthesis OR
- LDL delivery
What inhibits HMG-CoA reductase enzyme?
statins
What is not produced when statins inhibit the HMG-CoA reductase?
mevalonic acid
What is a lipoprotein?
protein and lipid containing particle, whose function isto shuttle lipid and lipid soluble antioxidants in the bloodstream to tissues where needed
What are the features of a lipoprotein?
- integral apoprotein
- hydrophilic surface of phospholipids + free cholesterol
- peripheral apoprotein
- hydrophobic core of triacylglycerols, cholesterol esters + lipid soluble vitamins
Where can lipoproteins be made?
- liver
- intestines
- tissues outside
- precursors in liver and gut
What are the lipoproteins in circulation called? (and where were they from)
- chylomicrons (gut)
- VLDL (liver)
- LDL/IDL (periphery)
- HDL (precursors in liver, formed in periphery)
What happens to most of the LDL?
absorbed by liver to lower serum LDL levels and reduce atherosclerosis
What happens as a result of high dietary cholesterol?
- high cytosolic cholesterol in liver cells
- HMG-coA inhibited
- LDL-R’s not produced, LDL not picked up
- LDL in circulation = elevated serum LDL + atherosclerosis
What happens in familial hypercholesterolemia?
- no working LDL receptors in liver (defect)
- LDL created stays in circulation (high levels + atherosclerosis)
- liver produces cholesterol
What are the protective roles of HDL?
- Stimulates macrophage cholesterol efflux
- Antiapoptotic
- Decrease expression of adhesion molecules (anti-inflammatory)
- Decrease LDL oxidation (antioxidative)
- Ameliorates endothelial function
How does HDL remove cholesterol from cholesterol-loaded macrophages?
by binding to ABCA1 and stimulating process of reverse cholesterol transport
What is the recommended UK NICE dietary intake of cholesterol?
less than 300mg/day
What is the total % fat intake recommended?
less than 30%
what is the recommended % saturated fats?
less than 7% total energy intake
What are saturated fats recommended to be replaced by?
mono-unsaturated fats and polyunsaturated fats
What is ezutimide?
- blocks intestinal absorption of cholesterol
- LDL decreases by 17-19%
- given in combination with statin
- but not proven so not approved by all yet
What are the benefits of phytosterols?
- reduce LDL 10% in 2 weeks
- taken 2g/day
- inhibits absorption of cholesterol and reabsorption of bile acids in gut
- more cholesterol taken from circulation in liver to replace bile acids
