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POM 2 Cell biology > 2.5 Cholesterol > Flashcards

2.5 Cholesterol Flashcards

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1
Q

What are the three primary sources of fats?

A
  1. The diet
  2. De novo biosynthesis (liver)
  3. Storage depots in adipose
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2
Q

What breaks down dietary fats?

A

Lipases

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3
Q

What are needed to solubilize dietary fats?

A

Bile acids

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4
Q

What does a lack of bile acids result in?

A

Steatorrhea (Fatty stool) - this is because majority of fat passes throuhg the gut undigested and unabsorbed

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5
Q

What produces bile salts?

A

Liver

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6
Q

What do bile salts do in digestion?

A

They emulsify fats in the intestine and aid the digestion of fat soluble vitamins (A, D, E and K)

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7
Q

What is Orlistat?

A

A potent inhibitor of gastric and pancreatic lipases

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8
Q

What is the main side effect of Orlisats?

A

Steatorrhea

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9
Q

what do lipoproteins do?

A

Transport lipids in the plasma

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10
Q

Where are chylomicrons produced and what is their role?

A

Intestine - dietary fat transport

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11
Q

Where are digested dietary products absorbed?

A

By the enterocytes that line the brush border of the small intestine

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12
Q

Where do chylomicrons acquire apoproteins from?

A

From HDL following release into the blood stream

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13
Q

How do chylomicrons enter into the blood stream?

A

Travel from the lacteals of the intestine into the thoracic duct and into the left subclavian vein from which they enter into the blood stream

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14
Q

What is the primary role of cholesterol in the body?

A

Maintenance of cell membrane integrity - can increase or decrease the stiffness depending on the temperature and nature of the membrane

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15
Q

How are all the physiological requirements for cholesterol met?

A

They are supplied by the liver thorugh the de novo synthesis of cholesterol from Acetyl CoA

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16
Q

What is the first step in cholesterol biosynthesis?

A

Condensation of 2 acetyl CoA into 1 acetoacetyl CoA
Catalysed by beta-ketothiolase

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17
Q

What is the second step of cholesterol biosynthesis?

A

Condensation of another Acetyl-CoA molecule to form HMG-CoA
Catalysed by HMG-CoA Synthetase

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18
Q

What is the third step in cholesterol biosynthesis?

A

HMG-CoA is reduced to generate mevalonate
Catalysed by HMG-CoA reductase

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19
Q

What enzyme is used to convert HMG-CoA into Mevalonate?

A

HMG-CoA Reductase

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20
Q

Describe how HMG CoA reductase is under negative feedback?

A

HMG-CoA reductase is inhibited by the end product cholesterol, bile salts and mevalonate

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21
Q

What is the fourth step in cholesterol biosynthesis?

A

Mevalonate undergoes sequential phosphorylation at the hydroxyl groups at position 3 and 5

Then decarboxylation to form 3-isopentenyl pyrophosphate

22
Q

What is the fifth step in cholesterol biosynthesis?

A

Isomerisation of isopentenyl PP into dimethylallyl PP

Condensation with isopentenyl PP to form C10 geranyl PP

Adding another isopentenyl PP to form C15 farnesyl PP

23
Q

What is the sixth step in cholesterol biosynthesis?

A

2 C15 farnesyl PP condense to form C30 squalene and 2 pyrophosphates

24
Q

What is the seventh step in cholesterol biosynthesis?

A

Squalene is reduced to squalene epoxide in presence of O2 and NADPH

Squalene epoxide lanosterol-cyclase catalyses formation of lanosterol

25
Q

What is the eighth step in cholesterol biosynthesis?

A

Lanosterol is reduced and 3 methyl groups are removed, forming cholesterol

26
Q

Why is ubiquinone confined to the inner membrane of the mitochondria?

A

Because it has lipophilic properties due to the isoprene unit

27
Q

What is cholesterol the precursor of?

A

Pregnenolone

28
Q

Describe the synthesis of Vitamin D from cholesterol?

A

7-dehydrocholesterol in the skin under UV is converted into Pre Vitamin D then cholecalciferol

Cholecalciferol then undergoes hydroxylation using 25-Hydroxylase to form 25-OH Cholecalciferol

1-alpha hydroxylase from the kidney produces 1,25(OH)2 Cholecalciferol (CALCITRIOL)

29
Q

What does calcitriol bind and induce?

A

Vitamin D response elements in promoter or target genes

Induces key genes in bone metabolism

30
Q

What are the names of the bile salts which are synthesized from cholesterol?

A

Cholesterol is converted by a series of reactions into the primary bile salt glycocholate and also taurocholate

31
Q

What does a deficiency of Vitamin D3 in childhood lead to?

A

Rickets

32
Q

What is HDL?

A

Cholesterol which takes cholesterol away from the peripheral tissue back to the liver for use or disposal

Helps to lower total serum choleterol

33
Q

What does prolonged levels of LDL lead to?

A

Atherosclerosis

34
Q

What do LDLs do

A

They transport chlesterol which has been made in the liver to the peripheral tissues - more than 40% weight is cholesterol esters

35
Q

What is reverse cholesterol transport?

A

When cholesterol is transported back to the liver by the actions of HDL

36
Q

Describe the pathophysiology of hypercholesterolaemia?

A

Patients lack functional LDL receptors

37
Q

How is hypercholesterolaemia treated?

A

Using resins and HMG-CoA reductase inhibitors

38
Q

What is an example of a HMG-CoA-Reductase inhibitor?

A

Statin

39
Q

How do resins work as a medication to contain hypercholesterolaemia?

A

Resins bind or sequester bile acid-cholesterol complexes preventing their reabsorption by the intestine

40
Q

What do fats need in order to be made soluble?

A

They need to be emulsified by bile

41
Q

What does the emulsification of large fat droplets result in?

A

The formation of micelles

42
Q

How do emulsified fat droplets form micelles?

A

Pancreatic lipase breaks down the triglycerides which have been emulsified into FFAs and monoglycerides

43
Q

Once pancreatic lipases have digested the emulsified fats, what happens next?

A

The free fatty acids and monoglycerides leave the micelle and enter into the enterocytes of the small intestine

44
Q

What happens to FFAs and MGs in the enterocytes of the mall intestine?

A

They reform triglycerides

45
Q

What forms inside the golgi of the enterocytes?

A

The fatty triglyceride globules combine with proteins to form chylomicrons

46
Q

Once the chylomicrons are extruded from the enterocyte what happens to them?

A

They enter into a lacteal and lymph in the lacteal transports chylomicrons away from the intestine

47
Q

After the chylomicron has left the enterocyte of the small intestine, what happens to it on the way to the liver?

A

The chylomicron starts making its way to the liver and picks up apoproteins from HDL

48
Q

What is the benefit of apoproteins binding to the chylomicron after it has left the enterocyte?

A

The chylomicron can bind to lipoprotein lipase which can metabolise the triglyceride component into free fatty acids and the glycerol

49
Q

What are the free fatty acids and glycerol used for?

A

Adipocytes - storage
Skeletal muscle - generate energy

50
Q

What happens to the chylomicron remanants?

A

They are sent back to the liver

POM 2 Cell biology (15 decks)

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