Cholesterol

Question 1

What is the general structure of cholesterol

Answer 1

Composed of 27 carbon atoms

Cyclic rings with a hydrophobic tail

Steroid ring is planar

Molecule is very hydrophobic apart from hydroxyl group

Question 2

What are some key properties of cholestrol

Answer 2

Increase and decrease membrane stiffness depending on temperature and nature of the membrane

Question 3

What are the three steps of cholestrol biosynthesis

Answer 3

1. Synthesis of isopentenyl pyrophosphate - activated isoprene unit which serves as a key building block
2. Condensation of six molecules of isopentenyl pyrophosphate to form squalene (cytoplasm)
3. Cylisation and demethylation of squalene by monooxygenases to give cholestrol

Question 4

What is HMG-CoA reductase under negative feedback by

Answer 4

Cholesterol, bile salts, mevalonate

Question 5

How does isoprene units allow cells to live in phospholipid layers

Answer 5

Confers lipophilicity

Question 6

What is the useful molecule starting building block for cholesterol

Answer 6

Question 7

What type of modification can proteins undergo

Answer 7

Prenylation (addition of farnesyl or a geranyl-geranyl moiety to C-terminal cysteine residues which gives them affinity for lipid bilayers.

Question 8

How does isoprene units useful in ubiquinone

Answer 8

Helps confien it to the inner membrane of the mitochondria

Question 9

What happens in cholestrol biosyntehsis 5

Answer 9

2 condesation reactions to form C15 intermediate

Question 10

How is squalene cyclized to cholestrol

Answer 10

1. Squalene is first reduced in the presence of oxygen and NAPDH to form squalene epoxide which has a different C=C bond distribution
2. 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

Question 11

What happens in cholesterol biosynthesis - 8

Answer 11

Lanosterol is subsequently reduced and three methyl units are removed

Question 12

What is the primary bile satl

Answer 12

Glycocholate

Taurocholate

Question 13

What enzyme catalyses the reaction of pregnenolone from cholesterol

Answer 13

desmolase

Question 14

What are the uses of cholesterol

Answer 14

Bile salts

Steroid hormones

Vitamin D

Question 15

What is familial hyeprchoelsterolaemia

Answer 15

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

Question 16

Diagram showing a cholesterol-rich plaque almost entirely blocking an artery

Answer 16

Question 17

Child with homozygous familial hypercholesterolaemia

Answer 17

Question 18

How to control hypercholesterolaemia

Answer 18

Inhibition of de novo cholestrol syntheiss by liver - resins

Reduction of dietary cholestrol absoprtion by the intestines - HMG-CoA Reducatase inhibitors

Question 19

What are resins or sequestratns

Answer 19

e.g. Cholestyramine

Bind or sequester bile acid-cholesterol complexes preventing reabsorption by the intestine

Lower LDL and raise HDL

Question 20

What are HMG-CoA-Reductase inhibitors

Answer 20

Statins e.g. lipitor, crestor

Molecule lovastatin - competitve inhibitor of HMG-CoA reductase

Question 21

What is the disease mechanism underlying FH

Answer 21

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