Biochemical Aspects of Liver Metabolism Flashcards

1
Q

Where is the first destination of most nutrients and xenobiotics absorbed from the GI tract?

A

Liver

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2
Q

What does the liver produce?

A

Bile

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3
Q

Name a plasma protein excreted from the liver?

A

Albumin

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4
Q

What two roles does the liver have in regulation of metabolism?

A
  1. Carbohydrate and lipid metabolism - fuel storage

2. Amino acid metabolism - urea cycle

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5
Q

What allows seperation of proteins by size?

A

Electrophoresis

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6
Q

What 4 plasma proteins can be seperated by electrophoresis?

A
  1. Albumin
  2. Alpha globulins
  3. Beta-globulins
  4. Gamma globulins
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7
Q

What substances maintan oncotic or colloid osmotic pressure?

A

Plasma proteins

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8
Q

What transports hydrophobic substances like steroid hormones, free fatty acids, bilirubin and cholesterol?

A

Plasma proteins

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9
Q

How can plasma proteins be involved with pH buffering?

A

Amino-acid side chains can carry net charges

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10
Q

What plasma proteins transport lipoproteins, lipids, hormones and bilirubin?

A

Alpha-globulins such as ceruloplasmin

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11
Q

What alpha-globulin, other than ceruloplasmin, transports vitamin A?

A

Retinol binding protein

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12
Q

What does deficiency of vitamin A cause?

A

Visual impairment

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13
Q

What is vitamin A converted to?

A

Retinaldehyde, part of rhodopsin, a visual pigment

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14
Q

Name two beta-globulins?

A

Transferrin and fibrinogen

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15
Q

What two things does transferrin do?

A

Transports Fe3+

Indicator of iron deficiency

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16
Q

What is an inactive form of fibrin and is involved in clotting of blood?

A

Fibrinogen

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17
Q

What is the most abundant plasma protein?

A

Albumin

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18
Q

How would you describe albumin?

A

Small, negatively charged, water-soluble

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19
Q

What is the main determinant of plasma oncotic pressure?

A

Albumin

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20
Q

What stimulates production of albumin in the liver?

A

Insulin

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21
Q

What are levels of albumin like in liver disease?

A

Low

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22
Q

What two factors can lead to low levels of albumin?

A

Starvation and low protein diets

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23
Q

What does albumin have multiple binding sites for?

A

Hydrophobic molecules

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24
Q

What is the affinity and capacity like for albumin?

A

Low affinity, but high capacity because of high concentration

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25
Q

Name three endogenous lipophilic substances that albumin transports?

A

Fatty acids
Bilirubin
Thyroid hormones

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26
Q

What important exogenous substances does albumin carry?

A

Aspirin

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27
Q

What special structural feature of albumin allows it to carry hydrophobic molecules?

A

Hydrophilic clefts in globular domains

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28
Q

What do haemoglobin, myoglobin and cytochromes all haev which is a key component?

A

Iron

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29
Q

How is iron transported?

A

As ferric ion Fe3+ bound ti transferrin

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30
Q

How is iron stored?

A

In cells bound to ferritin

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31
Q

What is an essential trace element?

A

Copper

32
Q

How is copper transported?

A

In blood bound to ceruloplasmin

33
Q

What disease is related to a copper/ceruloplasmin deficiency?

A

Wilsons disease

34
Q

What are two hydrophobic hormones?

A
Steroid hormones (derived from cholesterol)
T3/T4 thyroid hormones
35
Q

How is thyroxine transported?

A

Bound to thyroid-binding globulin

36
Q

How is cortisol transported?

A

Bound to cortisol-binding globulin

37
Q

What do transport proteins do to steroid hormones and T3/T4 thyroid hormones?

A

Extend biological half-life and increased plasma concentration

38
Q

What two substances are in teh core of lipoproteins (core of hydrophobic lipids)?

A

Cholesterol esters and triglycerides

39
Q

What two substances are in the shell of a lipoprotein?

A

Polar lipids and apoproteins

40
Q

What substances are involved in fat transport between organs and tissues?

A

Lipoproteins

41
Q

What is the density order for lipoproteins, starting with the least dense?

A

Chylomicrons, VLDL, IDL, LDL, HDL

42
Q

Where do chylomicrons originate and what is there function?

A

Intestine - transport of exogenous fat to liver

43
Q

Where does VLDL originate and what is its function?

A

Liver - transports endogenous fat to peripheral cells

44
Q

Where does IDL originate and what is its function?

A

VLDL - LDL precursor

45
Q

Where does LDL originate and what is its function?

A

VLDL/IDL/liver - cholesterol transport to peripheral tissues

46
Q

Where does HDL originate and what is its function?

A

Intestine/liver - reverse cholesterol transport

47
Q

What removes excess choleeterol from cells?

A

HDL

48
Q

How is cholesterol removed from cells?

A

Esterified with fatty acids, transported back to liver, excreted as bile salts via biliary system or faeces

49
Q

What is the only organ capable of metabolising and excreting cholesterol?

A

Liver

50
Q

What vitamin does the liver store for 10 months as retinol palmitate?

A

Vitamin A

51
Q

What vitamin does the liver store for 3 weeks?

A

Vitamin Dq

52
Q

What vitamin is stored in hte liver for a few years worth?

A

Vitamin B12

53
Q

What is cholesterol a precursor for (3 substances)?

A
  1. Bile acids
  2. Steroid hormones
  3. Vitamin D
54
Q

What is a major component of gall stones?

A

Cholesterol

55
Q

Where in cells is cholesterol synthesised?

A

In cytoplasm or enzymes bound to ER membranes

56
Q

What other three organs, than the liver, are involved in cholesterol synthesis?

A

Intestine, adrenal cortex and gonads

57
Q

What three things does synthesis of 1 mol of cholesterol require?

A
  1. Source of C atoms
  2. Source of reducing power
  3. Significant energy
58
Q

How many moles of acetyl-CoA is needed for 1 mol of cholesterol?

A

18 mol

59
Q

How many mol of NADPH is needed for 1 mol cholesterol?

A

16 mol

60
Q

How much energy is needed to make 1 mol of cholesterol?

A

36 mol of ATP

61
Q

What converts HMG CoA to mevalonic acid in cholesterol synthesis?

A

HMG-CoA reductase

62
Q

What does HMG-CoA reductase catalyse?

A

The reversible formation of mevalonic acid, so is rate limiting

63
Q

What is the synthesis and activity of HMG-CoA reductase stimulated by?

A

Fasting

64
Q

What does dietary cholesterol and high intrahepatocyte cholesterol do to HMG-CoA reductase?

A

Reduces activity

65
Q

What drugs target HMG-CoA reductase?

A

Statins

66
Q

What product from cholesterol has a role in the regulation of calcium and phosphorus metabolism?

A

Vitamin D

67
Q

What is the most abundant form of vitamin D in the circulatory system?

A

Vitamin D3

68
Q

Where are corticosteroids (21 carbon atoms) synthesised?

A

Adrenal cortex

69
Q

Where are androgens (19 carbon atoms) synthesised?

A

In testis

70
Q

Where are oestrogens (18 carbon atoms) synthesised?

A

In ovaries

71
Q

What is the main metabolic product of cholesterol?

A

Bile salts

72
Q

Where are bile salts synthesised and stored?

A

In liver

Stored as compoennet of bile in gall baldder

73
Q

What, once released into the duodenum, act as detergents for emulsifying ingested lipids?

A

Bile salts

74
Q

What agents bind bile salts and inhibit reabsorption in the enterohepatic circulation?

A

Anion exchange resins - cholestyramine

75
Q

What do anion exchange resins do to bile salt excretion and synthesis?

A

Increased bile salt excretion with increased synthesis of bile salts

76
Q

When there is increased synthesis of bile salts in teh liver, what does the concentration of cholesterol do?

A

Decrease and number of LDL receptors of hepatic cells increases

77
Q

When the number of LDL receptors of hepatic cells increases, what happens to the uptake of LDL cholesterol from plasma?

A

Increases leading to lower plasma LDL