Cholesterol Flashcards
What is the general structure of cholesterol
Composed of 27 carbon atoms
Cyclic rings with a hydrophobic tail
Steroid ring is planar
Molecule is very hydrophobic apart from hydroxyl group
What are some key properties of cholestrol
Increase and decrease membrane stiffness depending on temperature and nature of the membrane
What are the three steps of cholestrol biosynthesis
- Synthesis of isopentenyl pyrophosphate - activated isoprene unit which serves as a key building block
- Condensation of six molecules of isopentenyl pyrophosphate to form squalene (cytoplasm)
- Cylisation and demethylation of squalene by monooxygenases to give cholestrol
What is HMG-CoA reductase under negative feedback by
Cholesterol, bile salts, mevalonate
How does isoprene units allow cells to live in phospholipid layers
Confers lipophilicity
What is the useful molecule starting building block for cholesterol
What type of modification can proteins undergo
Prenylation (addition of farnesyl or a geranyl-geranyl moiety to C-terminal cysteine residues which gives them affinity for lipid bilayers.
How does isoprene units useful in ubiquinone
Helps confien it to the inner membrane of the mitochondria
What happens in cholestrol biosyntehsis 5
2 condesation reactions to form C15 intermediate
How is squalene cyclized to cholestrol
- Squalene is first reduced in the presence of oxygen and NAPDH to form squalene epoxide which has a different C=C bond distribution
- Enzyme squalene epoxide lanosterol-cyclase catalyses the formation of lanosterol. A series of 1,2-methyl group and hydride shifts along the chain of the squalene moelcuel which resuls in the formation of 4 rings
What happens in cholesterol biosynthesis - 8
Lanosterol is subsequently reduced and three methyl units are removed
What is the primary bile satl
Glycocholate
Taurocholate
What enzyme catalyses the reaction of pregnenolone from cholesterol
desmolase
What are the uses of cholesterol
Bile salts
Steroid hormones
Vitamin D
What is familial hyeprchoelsterolaemia
Monogenic dominan trait
Cholesterol transportation is defective
Contain a single copy of a mutant gene and have cholesterol levels approciamtley 2-3 times higher than normal
Susceptible to atheroscelorosis
Homozygotes are severly affects - serum cholesterol is fiver times higher and coronary infarction may be observed
Diagram showing a cholesterol-rich plaque almost entirely blocking an artery
Child with homozygous familial hypercholesterolaemia
How to control hypercholesterolaemia
Inhibition of de novo cholestrol syntheiss by liver - resins
Reduction of dietary cholestrol absoprtion by the intestines - HMG-CoA Reducatase inhibitors
What are resins or sequestratns
e.g. Cholestyramine
Bind or sequester bile acid-cholesterol complexes preventing reabsorption by the intestine
Lower LDL and raise HDL
What are HMG-CoA-Reductase inhibitors
Statins e.g. lipitor, crestor
Molecule lovastatin - competitve inhibitor of HMG-CoA reductase
What is the disease mechanism underlying FH
Mutations in several domains of the LDL receptor
Cholesterol is taken up by specific receptors LDLR
Over 1000 different LDLR mutations
Can affect either receptor expression, LDL binding or LDLR endocytosis and recycling
