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POM| Molecular Biology of The Cell > Cholesterol > Flashcards

Cholesterol Flashcards

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1
Q

Which 3 sources are fats derived from

A

Diet
De novo biosynthesis
Adipose tissue

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2
Q

Which group of enzymes break down dietary fats?

A

Lipases

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3
Q

What is the role of bile salts?

A

To emulsify fats aiding digestion and absorption (also of fat-soluble vitamins)

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4
Q

Which vitamins are fat soluble?

A

A, D, E and K

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5
Q

What is the result of lack of bile salts?

A

Majority of fat passing the gut undigested resulting in steatorrhea (fatty stool)

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6
Q

What is steatorrhea?

A

Excretion of fatty stool due to incomplete digestion of fats

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7
Q

Where is bile salt produced and stored?

A

Produced in liver, stored in gallbladder

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8
Q

What is the oral medication that is effective in treating obesity by inhibiting gastric and pancreatic lipases called?

A

Orlistat aka tetrahydrolipstatin

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9
Q

How does orlistat help with weight loss?

A

Reduces fat absorption by 30% as it is a potent inhibitor of gastric and pancreatic lipase

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10
Q

What are the side effects of orlistat?

A

Main side effects include abdominal pain, urgency to defecate, increased flatus and steatorrhea

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11
Q

What is synthesised as a transport molecule for dietary fats?

A

Chylomicron (CM)

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12
Q

What is a CM composed of?

A

Triglycerides, apoproteins (from HDL) and phospholipids (enclosing the triglycerides)

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13
Q

What is the route CM follow?

A

travel from the lacteals of the intestine to the thoracic duct and to the left subclavian vein where they enter the bloodstream

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14
Q

Which enzyme hydrolyses CM?

A

Lipoprotein lipase through recognition of apoproteins

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15
Q

Where is lipoprotein lipase found?

A

Located on the capillary endothelial cells lining a variety of tissues including adipose, heart and skeletal muscle

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16
Q

What happens to the contents of CM after hydrolysis?

A

Triglycerides → FA and Glycerol
FA undergo β-oxidation
Glycerol returned to liver for gluconeogenesis

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17
Q

What type of lipids is cholesterol?

A

Steroid

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18
Q

Where is majority of cholesterol located in?

A

More than 90% of cholesterol in the body is found in cell membranes regulating membrane stiffness bidirectionally

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19
Q

What is the dietary cholesterol uptake limit in humans approximately?

A

0.5 g/day

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20
Q

How are the physiological requirements for cholesterol supplied?

A

De novo synthesis of cholesterol from Acetyl CoA in the liver

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21
Q

What is the first of 3 main parts of cholesterol biosynthesis?

A

Synthesis of isopentenyl pyrophosphate, an activated isoprene unit which serves as a key building block (cytoplasm)

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22
Q

What is the second of 3 main parts of cholesterol biosynthesis?

A

Condensation of six molecules of isopentenyl pyrophosphate to form squalene (cytoplasm)

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23
Q

What is the third of 3 main parts of cholesterol biosynthesis?

A

Cyclisation and demethylation of squalene by monooxygenases to give cholsterol (ER)

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24
Q

Cholesterol Biosynthesis

Identify the step, enzyme and product

A

Step 1

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25
Q

Cholesterol Biosynthesis

Identify the step, enzyme and product

A

Step 2

26
Q

Cholesterol Biosynthesis

Identify the step, enzyme and product

A
27
Q

Cholesterol Biosynthesis

Identify the species providing negative feedback for this step

A
28
Q

Cholesterol Biosynthesis

Which step is rate limiting in cholesterol biosynthesis?

A

Step 3 - Production of Mevalonate from HMG-CoA

29
Q

Cholesterol Biosynthesis

What reactions does Mevalonate (6C) go through to produce isopentyl pyrophosphate (5C)?

A

Mevalonate undergoes sequential phosphorylation at hydroxyl groups at positions 3 and 5 followed by decarboxylation

30
Q

Cholesterol Biosynthesis

Identify the groups of enzymes used in each step according to the reactants

A

3 Kinases and 1 Decarboxylase

31
Q

Cholesterol Biosynthesis

What is the product of two consecutive condensation reactions of isopentenyl pyrophosphate (IPP)?

A

Farnesyl pyrophosphate (FPP) - 15C

32
Q

Cholesterol Biosynthesis

Identify the enzyme and product

A
33
Q

Cholesterol Biosynthesis

Identify the enzyme and product

A
34
Q

Cholesterol Biosynthesis

Identify all the intermediate products

A
35
Q

Which classes of steroid hormones arise from cholesterol?

A
36
Q

What is the name of precursor of steroid hormones that is derived from cholesterol and which enzyme catalyzes this reaction?

A
37
Q

Identify the condition needed to produce Vitamin D3 and the final product made from Vitamin D3?

A
38
Q

What is the result of Vitamin D3 deficiency in childhood?

A

Rickets - softening and weakening of bones

39
Q

What metabolism does calcitriol play a role in?

A

Calcium metabolism

40
Q

What are the major breakdown products of cholesterol?

A

Bile salts

41
Q

What are the source and role of VLDL?

A

Source - Liver
Role - Endogenous fat transport

42
Q

What are the source and role of IDL?

A

Source - VLDL
Role - LDL precursor

43
Q

What are the source and role of LDL?

A

Source - IDL
Role - Cholesterol transport

44
Q

What are the source and role of HDL?

A

Source - Liver
Role - Reverse cholesterol transport

45
Q

What are lipoproteins composed of?

A

Phospholipid monolayer containing cholesterol and apoproteins + a core of triacyl glycerols and cholesterol esters

46
Q

What are the reactants and ezyme needed to produce cholesterol ester?

A

phosphatidylcholine (lecithin)
LCAT (lecithin cholesterol acyltransferase)

47
Q

How is VLDL converted into LDL?

A

triacyl glycerols removed from VLDL → IDL → cholesterol esters added from HDL → LDL

48
Q

What is meant by reverse cholesterol transport?

A

Function of HDL - collecting cholesterol from tissues. back to the liver

49
Q

Why is LDL called bad cholesterol?

A

More than 40% of its weight is made up of cholesterol esters - elevated LDL levels lead to atherosclerosis

50
Q

Which 2 lipoproteins provide FFA for the adipose tissue?

A

CM and VLDL

51
Q

Which 3 lipoproteins provide FFA or cholesterol for the peripheral tissue?

A

CM, VLDL and LDL

52
Q

Where are the CM remnants collected?

A

Liver

53
Q

What happens to LDL remnants that are not cleared by the liver?

A

Cleared by macrophages

54
Q

What is the inheritance pattern of familial hypercholesterolaemia (FH)?

A

Autosomal dominant

55
Q

What is observed in patients with one or two copies of FH gene compared to non-carriers?

A

One mutant gene - serum cholesterol 2-3 times higher
Two mutant genes - serum cholesterol 5 times higher
Increased incidence of Atherosclerosis and coronary infarcts

56
Q

What are the physiological symptoms of FH?

A

Xanthomas - deposition of extra cholesterol into macrophages of skin
Coronary Plaques - shown in picture B

57
Q

Which molecule is affected in FH?

A

LDL receptor (LDLR)

58
Q

How is LDL transported inside the cell?

A

Receptor mediated endocytosis

59
Q

Identify the locations/types of mutations that result in FH

A
60
Q

Identify appropriate outcomes of given mutations for FH

A
61
Q

What medication could control hypercholesterolaemia by limiting cholesterol biosynthesis?

A

Statins - Lipitor (Pfizer) or Crester (AZ)
They behave in a similar way to Mevalonate to inhibit HMG-CoA Reductase in the rate-limiting step

62
Q

What medication could control hypercholesterolaemia by limiting cholesterol reabsorption?

A

Resins/sequestrants - Cholestyramine (Questran, Prevalite)
They bind to bile acid-cholesterol complexes to prevent reabsorption by intestines
Lowers LDL by 15-30%
Raises HDL by 3-5%

POM| Molecular Biology of The Cell (10 decks)

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