Cholesterol

Question 1

How many carbon atoms compose cholesterol?

Answer 1

27 carbon atoms

Question 2

What is the structure of cholesterol?

Answer 2

27 carbon atoms, consists of cyclic rings with a hydrophobic tail steroid ring
Carbon and hydrogen,
C3 hydroxyl group

Question 3

Why is cholesterol important?

Answer 3

Fluid dynamics within phospholipid bilayer, enables mechanical stability & fluidity

Question 4

How does cholesterol maintain fluid stability within the phospholipid bilayer?

Answer 4

The cholesterol ring system interferes with motions of the fatty acid side chains

Question 5

What is the first step of cholesterol synthesis?

Answer 5

Isopentenyl pyrophosphate- activated isoprene synthesis

Question 6

What is the second stage of cholesterol synthesis?

Answer 6

Condensation of 6 molecules of isopentenyl pyrophosphate to form squalene (cytoplasmic reactions)

Question 7

What is the fate of squalene?

Answer 7

Squalene undergoes demethylation and cyclisation to give cholesterol by monooxygenases

Question 8

How is isopententyl pp formed (stage 1 &2)?

Answer 8

Two molecules of acetyl-CoA condense to form four carbon acetyoacyl-CoA

This is added to acetyl-CoA

Forms 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA)

Converted into isopentenyl

Question 9

What happens to HMG-CoA?

Answer 9

HMG-CoA reductase reduces HMG-CoA into Mevalonate

Question 10

Which molecule provides the reducing power for the reduction of HMG-CoA into Mevalonate?

Answer 10

NADP+

Question 11

Where does reduction HMG-CoA occur within a cell?

Answer 11

Within the cytoplasm

Question 12

What is the fate of mevalonate?

Answer 12

Undergoes sequential phosphorylation at hydroxyl groups attached to c3 and c5 by kinase; decarboxylated into Isopenenyl-PP

Question 13

What molecule is consumed for the phosphorylation of mevalonate?

Answer 13

ATP

Question 14

What is the first step of squalene formation after isopentyl-PP is formed?

Answer 14

2 molecules of isopentenyl-PP condense to form dimethylallyl-pp

Question 15

What happens to dimethylallyl-pp?

Answer 15

Addition of isopentenyl to form 15 carbon species

Question 16

What enzyme catalyses the farnesyl-pp reaction?

Answer 16

Geranyl transferase

Question 17

What is the term for the 15 carbon compound formed from 3 isopentenyl-pp?

Answer 17

Farnesylpp

Question 18

How is squalene formed?

Answer 18

2 molecules of Farnesyl-pp condense, by squalene synthetase

Question 19

Where does demethylation and cyclisation of squalene occur?

Answer 19

Endoplasmic reticulum

Question 20

What is the fate of squalene?

Answer 20

Reduced in the presence of oxygen and NADPH, forms squalene epoxide

Question 21

How is cholesterol formed from squalene?

Answer 21

Squalene –> squalene epoxide –> lanosterol –> cholesterol

Question 22

What does cholesterol decompose into?

Answer 22

Glycocholate, taurocholate

Question 23

What are steroid hormones derived from?

Answer 23

Cholesterol

Question 24

What 5 classes of steroid hormones derive from cholesterol?

Answer 24

Oestrogens
Androgens
Corticosteroids
Mineralcorticoids
Progesterones

Question 25

What is the role of cholesterol in vitamin-D synthesis?

Answer 25

7-dehydrodcholesterol within epidermis --> provitamin-d3 --> Vitamin-d3 --> calcitriol

Question 26

What is familial hypercholesteroaemia?

Answer 26

Monogenic dominant trait, cholesterol transportation is defective

Question 27

What type of mutation is FH?

Answer 27

Loss of function in the LDL-receptor gene

Question 28

How can FH be controlled?

Answer 28

Inhibition of de no cholesterol synthesis in the liver | Reduction of dietary cholesterol absorption

Question 29

What drug can reduce cholesterol synthesis?

Answer 29

HMG-CoA-Reductase inhibitors (Statins) Resins(Sequestration of bile acid complexes)

Question 30

What is lovastatin?

Answer 30

Statins are a competitive inhibitor of HMG-CoA reductase, resembles 3-HMG, thus mevalonate cannot be synthesised

Question 31

What are resins (cholestryamine) ?

Answer 31

Bind or sequester bile-acid cholesterol complexes, prevents their reabsorption by the intestine

Question 32

Orlistat function?

Answer 32

Inhibition of pancreatic and gastric lipases

Question 33

How do chylomicrons enter the bloodstream?

Answer 33

Lacteals of the intestine to the thoracic duct and to the left subclavian vein where they enter the bloodstream

Question 34

How are chylomicrons incorporated into tissues?

Answer 34

Lipoprotein lipase

Question 35

What are the 3 *major* steps of cholesterol synthesis?

Answer 35

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

Question 36

How is cholesterol transported in LPs?

Answer 36

As cholesterol esters

Question 37

Life cycle of VLDLs, LDLs, IDLs and HDLs

Answer 37

Question 38

How do serum cholesterol levels vary with different types of FH?

Answer 38

Heterozygous: 2-3x - Atherosclerosis in mid age Homozygous: 5x - Atherosclerosis in adolescence

Question 39

How is LDL endocytosed?

Answer 39

1. Binding to LDLR 2. Endocytosis 3. Clathrin coat is uncloated 4. Fusion with endosome 5. Transfer to lysosome 6. Budding off to transport vesicles 7. Return of LDL to membrane+exocytosis

Question 40

What is HMG CoA inhibited by?

Answer 40

Statins, mevalonate, cholesterol, bile salts

Question 41

What are the 5 major classes of FH?

Answer 41

Question 42

What is the purpose of LCAT?

Answer 42

Creating cholesterol esters