Metabolism 7-8

Question 1

What does cholesterol do?

Answer 1

Influences membrane stiffness and permeability dependent on temperature and nature of the membrane. Stiffness normally increases with temperature. Also changes interactions with the cytoskeleton.

Question 2

How is cholesterol formed?

Answer 2

1) Activated isoprene unit (isopentenyl pyrophosphate) is made from acetyl-CoA units.
2) Six units of isopentenyl pyrophosphate are condensed to form squalene
3) Squalene is reduced in the presence of oxygen and NADPH to form squalene epoxide
4) Squalene epoxide lanosterolcyclase catalyses the formation of lanosterol
5) Lanosterol is then reduced and three methyl units are removed, forming cholesterol

Question 3

What is the precursor to all steroid hormones?

Answer 3

Pregnenolone

Question 4

What are the five forms of steroid hormones?

Answer 4

• Androgen
• Progesterone
• Glucocorticoids
• Mineralocorticoids
• Oestrogens

Question 5

How is cholesterol linked to calcium?

Answer 5

Cholesterol is the precursor to calcitriol, which plays an important role in calcium metabolism.

Question 6

What do lipoproteins contain?

Answer 6

Cholesterol and apoproteins.

Question 7

What are cholesterol esters?

Answer 7

An even more hydrophobic version of cholesterol that cause even tighter packaging of lipoproteins.

Question 8

How are cholesterol esters synthesised?

Answer 8

They are synthesised from cholesterol and an acyl group using lethicin.

Question 9

What are chylomicrons?

Answer 9

A form of lipoprotein that travel from lacteals in the intestine to the thoracic duct and subclavian vein where they re-enter the bloodstream.

Question 10

What is lipoprotein lipase?

Answer 10

An enzyme located on capillary endothelial cells in adipose, heart and skeletal tissue. It catalyses the hydrolysis of triacylglycerides into glycerol and fatty acids in chylomicrons.

Question 11

How does HDL cholesterol work?

Answer 11

• Often referred to as “good” cholesterol
• Takes cholesterol from peripheral tissue and transports it back to the liver for excretion or use
• Helps to lower serum cholesterol levels

Question 12

How does LDL cholesterol work?

Answer 12

• Often referred to as “bad” cholesterol
• Prolonged elevation of LDL levels can increase the risk of ahterosclerotic plaques
• Transports synthesised cholesterol from liver to the peripheral tissues

Question 13

What is familial hypercholesterolaemia?

Answer 13

• Monogenic dominant trait
• Single mutant copy = 2-3x higher cholesterol levels and increased risk of atherosclerosis and coronary infarctions.
• Two mutant copies - 5x higher cholesterol levels and atherosclerotic plaques are seen in adolescence

Question 14

What is familial hypercholesterolaemia caused by?

Answer 14

Lack of or non-functional LDL receptor on the surface of liver cells so LDL levels are not recognised, therefore LDL cholesterol is not scooped up.

Question 15

How is familial hypercholesterolaemia treated?

Answer 15

Statins, resins and sequestrants.

Question 16

How are proteins directed to the right place?

Answer 16

Signal sequences

Question 17

What are signal sequences?

Answer 17

Like postage labels. Short peptide sequences which are recognised by certain cells.

Question 18

How are abnormal proteins controlled?

Answer 18

Misfolded proteins are retained in the ER and degraded before deposited back into the cytoplasm.

Question 19

What is a disorder caused by a misfiled protein? Give details.

Answer 19

Cystic fibrosis

• Mutation on the CFTR gene caused by deletion of three nucleotides
• Phenylalanine is not coded for, causing the protein to mis-fold
• Causes problems in chloride ion channels in the airways/lungs and ducts.

Question 20

What does dynamin do?

Answer 20

A special protein that is involved in the unshedding of a vesicle coat. Forms around the neck, contracts and cleaves it off.