Cholesterol

Question 1

What does steroid structure look like

Answer 1

The steroid structure consists of four planar carbon ring that is very hydrophobic due to the C and H it contains, to which side groups can be added to form different steroids

Question 2

Where is cholesterol for physiological requirements in body synthesised

Answer 2

Cholesterol for physiological requirements in synthesised in the liver

Question 3

In what three parts can the biosynthesis of cholesterol be split

Answer 3

The biosynthesis of cholesterol can be split into 1. the synthesis of isopentenyl pyrophosphate, 2. the condensation of isopentenyl pyrophosphate to form squalene, 3. the cyclisation and demethylation of squalene to form cholesterol

Question 4

Where do these steps of cholesterol synthesis take place

Answer 4

The synthesis of isopentenyl pyrophosphate takes place in the cytoplasm, the formation of squalene and then cholesterol take place in the endoplasmic reticulum

Question 5

What are the end products from step 1 and 2 of cholesterol synthesis

Answer 5

The end product of step 1 is acetoacetyl-coA and HS-coA and of step 2 the end product is 3-hydroxy-3-methylglutaryl-coA (HMG-coA) and HS-coA

Question 6

After double condensation of Acetyl-CoA, what is product

Answer 6

The product of double condensation of acetyl-coA is 3-hydroxy-3-methylglutaryl-coA (HMG-coA)

Question 7

Which reducing agent is used to reduce this substance and what is the product in step 3 of cholesterol synthesis

Answer 7

NADPH is used to reduce HMG-coA and the product is mevalonate, and byproducts NADP+ and HS-coA

Question 8

What is the enzyme that catalyses this reaction and how is it controlled

Answer 8

HMG-coA reductase catalyses this reaction and is controlled via product inhibition by its product mevalonate, its ultimate end product cholesterol and bile salts

Question 9

What happens to mevalonate to form 3-isopentyl pyrophosphate

Answer 9

Mevalonate undergoes sequential phosphorylation (three times) and then a decarboxylation and dephosphorylation to form 3-isopentyl pyrophosphate

Question 10

What do isoprene units attached to molecules confer to these biomolecules

Answer 10

Isoprene units can be attached to molecules to make them have hydrophobic lipophilicity and be able to sit in lipid bilayers

Question 11

Where and what for is dolichol phosphate used

Answer 11

Dolichol phosphate is a lipid in the endoplasmic reticulum that is involved in the N-linked glycolysation of proteins

Question 12

How is ubiquinone (coenzyme Q) confined to inner membrane of mitochondrion

Answer 12

Ten isoprene units are added to pre-coenzyme Q to confer it the lipophilicity it needs to sit in the mitochondrial inner membrane

Question 13

What are the products of condensation reactions of two and three 3-isopentyl pyrophosphate groups called

Answer 13

The products of condensation of two 3-isopentyl pyrophosphate is geranyl pyrophosphate and when a third 3-isopentyl pyrophosphate is added this produces farnesyl pyrophosphate

Question 14

How many carbons is squalene and how is it synthesised

Answer 14

Squalene consists of 30 carbon atoms and is formed after the condensing of two farnesyl phosphate molecules with NADPH as reducing agent

Question 15

In the last part of cholesterol synthesis, how is lanosterol changed to cholesterol

Answer 15

Lanosterol is converted to cholesterol in 19 steps that result in three times demethylation and reduced to form cholesterol

Question 16

Which type of enzymes are involved in the last step of cholesterol synthesis

Answer 16

Moxooxygenases and cyclases are involved in the last step of cholesterol synthesis to induce the cyclation of squalene to lanosterol which is then further converted to cholesterol

Question 17

In what primary bile salt can cholesterol be converted and what other bile salt

Answer 17

Cholesterol can be converted in the liver to form primary bile salt glycocholate or can also be converted to taurocholate

Question 18

What precursor is made from cholesterol to form steroid hormones

Answer 18

Cholesterol can be converted by desmolase to pregnenolone which is the precursor for all five classes of steroid hormones

Question 19

What are the five classes of steroid hormones

Answer 19

The five classes of steroid hormones are progestagens, glucocorticoids, mineralocorticoids, androgens and oestrogens

Question 20

What types of substances are vitamin D and what are they used for

Answer 20

Vitamin D are a group of steroid compounds that bind to intestinal wall to allow for the uptake of ions like calcium, phosphate and magnesium that are needed for bone development.

Question 21

How is calcitriol synthesised and what is its function

Answer 21

Calcitriol is synthesised from cholecalciferol (vitamin D3) by twice hydroxylation and this active form of vitamin D can bind to vitamin D binding elements in nucleus and induce transcription of key genes for bone development

Question 22

What is rickets and what is its cause

Answer 22

A development disease due to deficiency of vitamin D3 during childhood that leads to abnormal bone formation with soft and weak bones

Question 23

What is prenylation

Answer 23

Prenylation is a post-translational modification in which a farnesyl or geranyl-geranyl group is added to a cysteine residue

Question 24

How is the emulsification function of bile salts enabled

Answer 24

When cholesterol is converted in the liver, a hydrophilic group is added to its tail, a carboxyl group in glycocholate and a sulfate group in taurocholate

Question 25

What type of genetic disorder is familial hypercholesterolaemia

Answer 25

Familial hypercholesterolaemia is a dominant monogenetic disorder

Question 26

What symptoms can be seen in heterozygous individuals with FH

Answer 26

In individuals with heterozygous FH two to three times higher blood cholesterol levels are found

Question 27

What symptoms can be seen in homozygous individuals with FH

Answer 27

In individuals with homozygous FH more than five times higher blood cholesterol levels are found and often coronary infarction and severe atherosclerosis occur already in adolescence

Question 28

What is a xanthoma

Answer 28

Xanthomas are cholesterol-rich superficial fatty deposits due to high LDL levels that lead to scavenging and deposits by macrophages that become foam cells

Question 29

What receptor is dysfunctional in FH and how many mutations can cause this disorder

Answer 29

In familial hypercholesterolaemia the LDL receptor that is found on hepatocytes and other somatic cells is dysfunctional. This can be caused by more than thousand different mutations.

Question 30

What things can happen to the receptor because of these mutations

Answer 30

The mutations that lead to FH can affect LDLR synthesis and expression, LDL binding, LDLR recycling and endocytosis which can all lead to FH

Question 31

What is the effect of resins on cholesterol levels

Answer 31

Resins prevent the reuptake of cholesterol-bile acid complexes, lowering LDL by 15-30% and increasing HDL by 3-5%

Question 32

Which enzyme do statins inhibit and how and what is its function

Answer 32

Statins bind to HMG-coA reductase and it inhibits the formation of mevalonate by competitive inhibiting the enzyme that is involved in the cholesterol synthesis pathway, by which they decrease the cholesterol produced by the body