biochemistry 6

Question 1

what is the structure and characteristics of cholesterol

Answer 1

• steroid with 4 linked hydrocarbon rings
• hydrocarbon tail and hydroxyl group at opposite ends
• highly hydrophobic and insoluble in water

Question 2

what is the functions of cholesterol

Answer 2

• modulates membrane fluidity
• some nerve cells have 25% in the plasma membrane
• precursors to steroid hormones and bile salts

Question 3

where is cholesterol mainly synthesised and what does it require

Answer 3

• the liver
• ATP and NADPH

Question 4

what are the stages of cholesterol synthesis

Answer 4

1) acetyl CoA converted to mevalonate - cytoplasm

2) mevalonate is used to synthesise isopentenyl pyrophosphate - cytoplasm

3) 6 molecules of isopentenyl pyrophosphate condense to form squalene - ER

4) squalene cylizes to lanosterol

5) lanosterol converted into cholesterol - ER

Question 5

what is the name of the first step in cholesterol synthesis and what enzyme is used

Answer 5

• commitment step
• HMG-CoA reductase

Question 6

what is required for the second step of cholesterol synthesis

Answer 6

• 3ATP and one decarboxylation

Question 7

how many isomers of isopentenyl pyrophosphate are there and are they in equilibrium

Answer 7

• 2 isomers
• in equilibrium

Question 8

what is added in stage 3 of cholesterol synthesis and how do they combine

Answer 8

• two additional isopentenyl pyrophosphates added to form farnesyl pyrophosphate
• tail-tail coupling of farnesyl pyrophosphates yield squalene

Question 9

how is squalene activated

Answer 9

• activated with the formation of squalene epoxide

Question 10

what does squalene epoxide form

Answer 10

• protonated to form carbocation that cylizes to form a tetracyclic stricture

Question 11

what is HMG CoA reductase activity controlled by

Answer 11

• mRNA controlled by sterol regulatory element binding protein (SREBP)

Question 12

what happens when HMG CoA reductase becomes inactive

Answer 12

• high cholesterol
• SREBP bound to SREBP cleavage activating protein (SCAP) at ER

Question 13

what happens when cholesterol levels decrease

Answer 13

• SCAP escorts SREBP to the golgi
• golgi serine and matalloprotease act of SREBP
• DNA-binding domain moves to the nucleus to alter HMG CoA reductase gene expression

Question 14

what happens when cholesterol levels are high

Answer 14

• mRNA controlled by SREBP
• mRNA negative feedback by metabolites of mevalonate
• HMG CoA reductase degradation with high cholesterol
• AMP-activated kinase phosphorylates and inactives HMG CoA reductase

Question 15

what are the sources of cholesterol

Answer 15

• meats
• dairy products
• cakes and biscuits
• foods containing coconut oil or palm oil

Question 16

how is cholesterol absorbed in the body

Answer 16

• intestine by sterol transporters
• cholesterol esterified by Acyl-CoA-cholesterol acyltransferase-2
• incorporated into chylomicrons - lipoprotein

Question 17

what are lipoproteins

Answer 17

• soluble protein-lipid particles
• proteins component use to target to specific tissue

Question 18

what is a chylomicron

Answer 18

dietary lipids and cholesterol

Question 19

what is a low-density lipoprotein (LDL)

Answer 19

• supplies cholesterol to tissues
• receptor mediated endocytosis by LDL receptor binding internalisation (recycled after) and LDL hydrolysis

Question 20

what is a high-density lipoprotein

Answer 20

• removes free cholesterol from tissue
• transports cholesterol to liver

Question 21

what does the liver do with cholesterol

Answer 21

• eliminates cholesterol from the body as bile salts or unchanged

Question 22

what steroid hormones and vitamins does cholesterol make

Answer 22

steroid hormones - progesterone, testosterone, oestrogen, cortisol
vitamins - D, calcium, phosphorus

Question 23

what are bile salts

Answer 23

• detergents that render dietary lipids more accessible for digestion by lipase
• made from cholesterol

Question 24

what is dietary lipids function

Answer 24

• fatty acids are main lipid constituent of diet
• primary role in energy metabolism - beta oxidation and energy storage

Question 25

what is the luminal phase of degradation of dietary lipids

Answer 25

1) lipases secreted near tongue and stomach - some lipids hydrolysed into glycerol and free fatty acids

2) emulsification in the stomach - small lipid droplets form

3) bile salts used to form micelles allowing lipase access

4) pancreatic impasse complete hydrolysis in duodenum and jejunum

Question 26

what happens in the mucosal phase in the degradation of dietary lipids

Answer 26

• fatty acids —-> Acyl-CoA derivatives
• cytoplasmic surface of ER - esterifcation of fatty acids to triacylglycerol

monoacylglycerol + Fatty acyl-Co-A —-> diacylglycerol + fatty acyl-Co-A —–> triacylgycerol
1) monoacylglycerol transacylase
2) diacylglycerol transacylase

Question 27

what happens in secretion/ transport in the degradation of dietary lipids

Answer 27

1) in the gut, triacylglycerols accumulate in chylomicrons
2) chylomicrons exocytosed into blood via lymphatic system
3) blood lipase hydrolyse chylomicrons into fatty acids
4) fatty acids taken up by tissues
5) chylomicron remnants taken up by liver - rich in cholesteryl ester and fat soluble vitamins

Question 28

what do apolipoproteins do

Answer 28

• act like postcodes
• regulate lipase activity

Question 29

what stimulates/ decreases lipoprotein lipase activity

Answer 29

apoliproteins - apoC -1,2,3,5,E - stimulates activity
angiopoietin like proteins - ANGPTL3,4,8 - converts active lipase dimer to inactive monomers