Cholesterol Flashcards
What is cholesterol
Insoluble molecule essential for life as a precursor and constituent of membranes and membrane components and precursor for steroid hormones
What is the function of cholesterol in membranes
Moderates fluidity/stability
What are glucocorticoids
Class of cholesterol derivatives hormones that are able to increase serum glucose via gluconeogenesis
What are mineralocorticoids
Class of cholesterol derivatives hormones involved in water/salt balance
What are androgens and estrogens
Class of cholesterol derivatives hormones involved in development/ sexuality
What adds to the cholesterol pool
Dietary cholesterol
Cholesterol synthesis from all cells
Cholesterol synthesis and export to other cells by the liver
What reduces the cholestrol pool
Removal of cholestrol from the body by the liver
What is the only method of removal of cholestrol from the body
Via the liver
What is familial hypercholestrolaemia (FHC)
Autosomal dominant genetic condition which results in elevated serum cholesterol and leads to cardiovascular disease
Which form of FHC is treatable and develops later in life
Heterozygous
Which form of FCH is likely to develop cardiovascular disease prematurely
Homozygous
How is cholestrol transported
Exported from liver by VLDL and LDL to other cells
Why is cholestrol transported to other cells
Increase cholestrol load in peripheral tissues
How is cholestrol fed back to the liver from other tissue
HDLs
Why do other tissues feedback to the liver using HDLs
Decreases cholestrol load in peripheral tissues
What happens to excess cholesterol
Processed into bile acids or removed directly by exportation to gut
Why is processing/ removal of excess cholesterol important
Aids solubilisation of lipid nutrients
What is forward transport of cholestrol
Transport of ‘bad cholestrol’ using LDL from liver to cells (increases cell cholesterol)
What is reverse transport of cholesterol
Transport of ‘good cholestrol’ from cells to liver via HDL (lowers cell cholesterol)
Describe stage 1 of cholesterol synthesis
Synthesis of isopentenyl pyrophosphate
Describe stage 2 of cholestrol synthesis
Condensate of 6 molecules of isopentenyl pyrophospahte to form squalene
Describe stage 3 of cholestrol synthesis
Cyclisation of squalene and conversion into cholesterol
What are all 27C atoms in cholesterol ultimately derived from
Acetyl CoA
Where is the Acetyl CoA cholestrol is derived from produced
From glycolysis and TCA cycle via export of citrate and generation of acetyl CoA in cytoplasm
What is the function of HMG-CoA reductive in cholesterol synthesis
Produces Melvalonate which is a committed step in cholesterol biosynthesis (used to produce isopentenyl pyrophosphate)
Which drug targets HMG-CoA reductase
Statins
What are the major sites of cholesterol synthesis
Cytosol and microsomes of liver and intestine
What is the key to regulating cholesterol biosynthesis
HMG-CoA reductase control
How is HMG-CoA reductase controlled
By amount and activity of enzyme
Describe the processes involved in HMG-CoA reductase
Gene transcription
Rate of mRNa translation
Ubiquitination pathway (degrades protein)
Phosphorylation (rate of activity/energy status of cell)
Negative feedback fro, cholesterol in cell (allosteric inhibition)
How do statins affect HMG-CoA reductase
Structural analogues of HMG-CoA reductase so reversible competitive inhibitor
How is cholestrol disposed
Cannot be broken down so sterol nucleus must be removed before conversion to bile salts/removed via faeces to keep secreted cholesterol soluble
How do gallstones form
Failure to produce enough bile so cholesterol is less soluble and precipitates into gallstones and cholelithiasis
What is the most prominent role of vitamin D (cholestrol derived hormone)
Regulation of serum ca2+
What converts 7-dehydrocholesterol to vitamin D
UV light
Which 3 organs are involved in vitamin D synthesis
Skin, kidney and liver
How does vitamin D maintain serum ca2+ levels
Released in response to low serum ca2+ and targets gut cells to increase ca2+ absorption from diet so more is available for bone synthesis
What can cause ca2+ to be released from bone stores
Too much vitamin D
