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GIGU > Liver Biochemistry > Flashcards

Liver Biochemistry Flashcards

1
Q

Largest solid organ in the body?

A

Liver

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2
Q

What is the blood supply to the liver and percentage of each supply?

A 
75% = portal vein
25% = hepatic artery
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3
Q

What does the portal vein bring to the liver?

A

Nutrient rich blood

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4
Q

What does the hepatic artery bring to the liver?

A

Oxygen rich blood

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5
Q

The portal vein and hepatic artery mix in sinusoids. How does the blood leave the liver?

A

Inferior vena cava

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6
Q

How does bile leave the liver?

A

Flows out through the bile duct

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7
Q

6 liver cell types

A 
Hepatocytes
Endothelial cells
Kupffer cells
Stellate cells
Pit cells
Cholangiocytes
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8
Q

Job of hepatocytes?

A

Carry out most metabolic functions = main cell

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9
Q

Where will you find endothelial cells?

A

Lining the sinusoids

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10
Q

Describe endothelial cells that line sinusoids in the liver

A

Have fenestrations (pores) to allow for material exchange between hepatocytes and blood

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11
Q

Where will you find Kupffer cells?

A

Lining the sinusoids

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12
Q

Job of Kupffer cells?

A

They are macrophages that protect the liver from toxins via phagocytosis and remove dead RBCs
- contain lots of lysosomes

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13
Q

Job of Stellate (Ito) cells?

A

Storage of vitamin A and regulates contractility of sinusoids

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14
Q

During liver cirrhosis, what cell type can negatively impact liver function by producing fibril-producing collagen?

A

Stellate cells

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15
Q

Job of Pit cells?

A

Natural killer cells in the liver that defend against toxins

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16
Q

Where will you find cholangiocytes?

A

Lining the bile ducts in the liver

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17
Q

Job of cholangiocytes?

A

Control the bile flow rate and pH

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18
Q

Overall function of the liver?

A

Primary receiving, distributing and recycling center

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19
Q

The liver is important in many functions of metabolism. List some

A

Carbohydrate (glucose) metabolism
Lipid metabolism (creates TAGs, bile acids, bile salts and ketones)
Synthesis of blood proteins

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20
Q

How does liver manage waste?

A

Inactivation, detoxification and transformation of metabolites

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21
Q

What allows for greater access and increased contact between the liver cells and the blood?

A

Fenestrations and lack of tight junctions in the sinusoidal epithelium

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22
Q

3 main things that bile is made up of?

A

Cholesterol
Bile acids
Bile salts

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23
Q

What are bile acids and bile salts synthesized from?

A

Hepatic cholesterol

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24
Q

Pathway for bile?

A
  • Made in hepatocytes
  • Travel to bile canaliculi
  • Travel through bile ducts to gallbladder where they are stored
  • Released to duodenum in response to food
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25
Q

Bile acids are?

A

Protonated form

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26
Q

Bile salts are?

A

Deprotonated form

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27
Q

Do bile acids or bile salts do the emulsification of fats?

A

Bile salts

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28
Q

Describe the process bile salts take for the emulsification of fats

A

Bile acid ionizes to conjugate bile salt

  • Hydrophobic surface associates with TAG
  • Multiple of these join to form a micelle (aggregate)
  • Hydrophilic surface faces outward to associate with pancreatic lipases
  • Pancreatic lipases digest fatty acids so they can be absorbed in intestinal mucosa
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29
Q

Bile acids are formed from cholesterol. What are the main structural features of cholesterol?

A

4 rings and an OH group on carbon 3

30
Q

What is the first step and rate limiting step in bile acid synthesis?

A

7alpha-hydroxylase takes cholesterol to

7alpha-hydroxycholesterol

31
Q

What are the main structural features of

7alpha-hydroxycholesterol?

A

4 rings, an OH group on carbon 3 AND 7

32
Q

7alpha-hydroxycholesterol then creates what 2 primary bile acids?

A

Cholic acid

Chenodeoxycholic acid

33
Q

What are the main structural features of cholic acid?

A

4 rings, an OH group on carbon 3, 7, 12 and a COOH

34
Q

What are the main structural features of chenodeoxycholic acid?

A

4 rings, an OH group on carbon 3, 7 and a COOH

35
Q

The primary bile acids are then conjugated before secretion. Why?

A

The lower the pKa, the stronger the detergent effect

36
Q

What 2 groups may be added to either cholic acid or chenodeoxycholic acid to form the primary conjugated bile acids?

A

Glycine

Taurine

37
Q

If you add glycine to cholic acid or to chenodeoxycholic acid, what will you get?

A

Glycine + cholic acid = glycocholic acid

Glycine + chenodeoxycholic acid = glycochenodeoxycholic acid

38
Q

If you add taurine to cholic acid or to chenodeoxycholic acid, what will you get?

A

Taurine + cholic acid = taurocholic acid

Taurine + chenodeoxycholic acid = taurochenodeoxycholic acid

39
Q

List the 4 primary conjugated bile acids

A

Glycocholic acid
Taurocholic acid
Glycochenodeoxycholic acid
Taurochenodeoxycholic acid

40
Q

List the 2 primary bile acids

A

Cholic acid

Chenodeoxycholic acid

41
Q

Primary conjugated bile acids are then changed to what?

A

Primary bile salts for emulsification

42
Q

What can deconjugate/dehydroxylate primary bile salts?

43
Q

Bacteria deconjugates/dehydroxylates primary bile salts into what?

A

Primary and secondary bile acids

44
Q

What absorbs the primary and secondary bile acids for recycled use in the liver?

45
Q

What are the secondary bile acids?

A

Deoxycholic acid

Lithocholic acid

46
Q

What are cholesterol lowering drugs?

A

Bile acid - binding resins

47
Q

What do bile acid - binding resins do?

A

Cause an increase in the excretion of bile acids

48
Q

How do bile acid- binding resins can an increase in the excretion of bile acids?

A

They cause an increase in bile acid synthesis which then depletes the liver cholesterol pool and lowers the plasma cholesterol levels

49
Q

Gallstones are made of?

A

Bile crystals with lots of cholesterol

50
Q

Insufficient secretion of bile salts from the gallbladder OR excess cholesterol secretion into the bile

A

Cholelithiasis

51
Q

Xenobiotic

A

Ingested compounds with no nutritional value

52
Q

Metabolites

A

Compounds made in the body

53
Q

Liver is the primary site for conversion/degradation of?

A

Xenobiotics and metabolites

54
Q

What are the phases for inactivation of xenobiotics?

A

Phase 1 = increase polarity (add OH)

Phase 2 = add functional group to make safe for excretion

55
Q

What catalyzes phase 1 reactions for inactivation of xenobiotics?

A

Cytochrome P450 = CYPs (enzymes)

56
Q

What version of CYP metabolizes the greatest number of drugs?

57
Q

Agents that inhibit CYP will cause?

A

Increase in drug levels

58
Q

Agents that stimulate CYP will cause?

A

Decrease in drug levels

59
Q

Ex. of a CYP inhibitor on statin drugs

A

Grapefruit juices

60
Q

Grapefruit juices will ____ statin levels

61
Q

Ex. of a CYP stimulator on statin drugs

A

St. Johns wort

62
Q

St. Johns wort will _____ statin levels

63
Q

Variations in responses to drugs and drug metabolism is based on?

A

CYP polymorphisms between people

64
Q

CYP3A4 oxidizes ____ to NABQ1 that will damage hepatocytes

A

Excess Tylenol

65
Q

Disease of the liver cause impairment of what?

A

Free exchange of material between blood and hepatocytes due to fibrillar collagen

66
Q

Excess tylenol is converted to NABQ1 by CYP3A4. NABQ1 is normally detoxified by?

A

Glutathione

67
Q

With a tylenol overdose, what is the antidote to destory NABQ1?

A

N-acetyl cystein

68
Q

pKa of glycocholic acid

69
Q

pKa of taurcholic acid

70
Q

What is the stronger detergent, glycocholic acid or taurocholic acid?

A

Taurcholic acid because it has a lower pKa!

71
Q

What is an example of a non-absorbable bile acid - binding resin that is used to treat high cholesterol?

A

Cholestyramine

72
Q

What does cholestyramine do?

A

Binds bile acids to excrete them because it is non-absorbable; (most bile acids are reabsorbed); this causes an increase in bile acid synthesis and depletion of cholesterol levels!

GIGU (29 decks)

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