Liver Metabolism Flashcards Preview

Hugh's MD1 Abdominal > Liver Metabolism > Flashcards

Flashcards in Liver Metabolism Deck (85):
1

What colour is P450?

Red because of the iron protoporphyrin molecule which hemoglobin also has

1

Why doesn't phototherapy work for older people?

Their skin is too thick for the light to penetrate

1

What is haemoglobin with Fe3+ called?

Methaemoglobin

2

What type of enzyme are P450?

Monoxygenase

2

How does a bruise appear after 5-10 days?

Greenish/yellowish - due to biliverdin

2

What makes conjugated bilirubin soluble?

Hydrophilic glucuronate

3

What is the implications of substances inducing its P450?

Can lead to the development of resistance to the drug or

Some people may be poor metabolises of a drug

3

How does a bruise appear after 1-2 days?

Bluish-purple/blackish

3

How can you treat Crigler-Najjar syndrome?

Fluorescent light therapy

Liver transplant

 

3

What is the major colourant of faeces?

Stercobilin

4

How does a bruise appear after 10-14 days?

Yellow-brown or light brown (bilirubin)

6

How do mitochondria appear when centrifuged?

A straw to red colour

6

What is special about CYP2D6?

It metabolising aprox. one quarter of all pharmaceuticals

6

What is the function of the mononuclear phagocyte system?

Destruction of old RBCs and WBCs

Formation of plasma proteins

Formation of antibody

Formation of bile pigment

7

What are the implications of low hemopexin?

Haemolytic anaemia

8

In general, how do cytochromes carry O2?

Fe2+ <> Fe3+

10

How are different P450 systems named?

CYP [number][letter][number]

CYP means cytochrome P450

And the latter are for family, subfamily and form respectively

11

How is urobilinogen made?

By the action of commensals in the gut

13

Which disease is aflatoxin associated with?

Kwashiorkor

13

What percentage of RBC turn over occurs outside the spleen?

10%

14

What does haem oxygenase resemble?

Globin

15

How long due RBCs last in the blood stream?

120 days

15

What does haemolytic crisis result in?

Anaemia

Jaundice

16

What happens to benzopyrene?

Can either be inactivated and safely secreted or

Activated into a carcinogen

17

What converts haem into biliverdin?

haem oxygenase

19

What determines whether the liver or the immune system will deal with a foreign substance?

The liver handles molecules <5000 molar mass

21

What is the role of Fe2/3 in the P450 cycle?

Take and pass e- to make the ROS

23

Why is it called the P450 system not enzyme?

Because two enzymes are required for the process to occur

24

How much urobilinogen is excreted through the kidney?

1%

25

What is a cause of haemolytic disease in newborns?

Maternal ab crossing the placenta and reacting with foetal RBCs

27

What is the ROS created in the P450 cycle?

Peroxide

27

What role does albumin play in haem metabolism?

Carries unconjugated bilirubin to the liver

28

What is haem first converted into?

Biliverdin

28

What is the mononuclear phagocyte system?

Immune cell mediated system consisting of monocytes, macrophages, and to a lesser extent T and B cells in the lymph nodes, spleen and liver.

28

What is the function of cMOAT?

Transport conjugated bilirubin from hepatocytes into liver canaliculi 

29

What is commonly added to substrates?

-OH group

30

Where is EPO synthesized?

The kidney

31

What is the function of P450 reductase in the P450 cycle?

Facilitate the supply of electrons from NADPH to O

31

What is makes up the structure of bilirubin?

4 pyrrole rings

33

What are microsomes?

The in vitro isolated form of P450 cytochromes

34

What enzyme is required for the conjugation of bilirubin?

UDP glucuronyl transferase

34

What carries iron to the liver/bone marrow after RBC destruction?

Transferrin

36

How many genes for P450s have been identified?

57

37

What does the P in P450 stand for?

Pigment

39

What colour bilirubin?

Yellow

40

At defect in what causes Crigler-Najjar disease

UDP glucuronyl transferase 

41

What reaction does P450 typically catalyse?

RH + NADPH + O2 + H+ > ROH + NADP+ + H2O

42

What happens when bilirubin is exposed to light? What are the implications of that?

Double bonds isomerize making it more soluble.

 

Phototherapy can be used to treat jaundice

43

Where does aflatoxin come from in the diet?

Aspergillus fungus on corn or peanuts

43

What are the 3 signs of RBC aging?

Loss of sialic acid residues from glycophorin

Phosphatidylserine flips to the other side of the membrane

Oxidative damage eg Heinz bodies

45

What initiates P450 reaction cycle?

A substrate binding to P450

47

Where does the P450 process typically occur?

Smooth ER of hepatocytes

48

What is the purpose of the P450 cycle?

Create a ROS next to the substrate

49

What happens to free haemoglobin if haptoglobin is depleted?

It is excreted in the urine

50

What is the function of hemopexin?

It carries free haem to the liver

51

How many RBCs are made per second?

2 million

52

What is Crigler-Najjar syndrome caused by?

Mutation causing inactivation of glucuronyltransferase

54

Where is bilirubin usually produced?

Spleen

55

How long does it take reticulocytes to mature into RBCs?

1 day

57

How is the lifespan of RBCs calculated?

Tagging them with radioactive chromiun

59

What provides the electrons in the P450 cycle?

NADPH

60

What is kernicterus?

Neurotoxic damage due to high levels of bilirubin in the children

61

Where in the spleen does RBC breakdown occur?

Red pulp

62

Do reticulocytes have nuclei?

No

63

Why are P450 types specific to certain substrates?

The binding cleft must be specific for the substrate

64

What percentage of the population doesn't response to codeine?

10%

64

What is the problem with high levels of bilirubin in children?

It's neurotoxic

65

What are the physiological consequences of haemolysis

 

Unconjugated hyperbilirubinaemia as the liver's capacity to metabolise Hb is saturated

Increase stercobilin in stool and urobilinogen in urine

Reticulocytosis

66

How much of the circulating blood are reticulocytes?

1%

67

In what form is bilirubin reabsorbed in the gut for excretion through the kidneys

Urobilinogen

68

What are some causes of hyperbilirubinaemia

Bile duct obstruction

Severe liver failure due to cirrhosis

Dubin-Johnson syndrome

69

What colour is urobilinogen?

Colourless

71

What converts biliverdin to bilirubin?

Biliverdin reductase

73

Which cell breaks down senescent RBCs?

Macrophages

74

What do mitochondria use P450 for?

Oxidising steroids

75

What is Dubin-Johnson syndrome caused by?

A genetic defect in cMOAT

76

What is haptoglobin?

Plasma protein that binds to haemoglobin for RBCs that break down outside the spleen.

77

What are the two forms of bilirubin?

Conjugated (direct)

Uncojugated (indirect)

78

Where are P450 cytochromes located within cells?

ER 

Mitochondria

80

What happens to the haptoglobin-haemoglobin complex?

Removed with the mononuclear phagocyte complex mostly in the spleen

81

Why must there be many different type of P450?

Because they are specific to different substrates

82

Which P450 is deficient in individuals that have difficulty converting codeine to morphine?

CYP 2D6

83

What is the outcome of the ROS reacting with the substrate?

-OH added most commonly

Sometimes can cause others eg epoxide

84

What types of molecules does albumin bind?

Hydrophobic

85

What is are the implications of low haptoglobin in the blood?

High levels of haemolysis is occurring