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Hugh's MD1 Abdominal > Liver Metabolism > Flashcards

Liver Metabolism Flashcards

(85 cards)

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1
Q

What colour is P450?

A

Red because of the iron protoporphyrin molecule which hemoglobin also has

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1
Q

Why doesn’t phototherapy work for older people?

A

Their skin is too thick for the light to penetrate

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1
Q

What is haemoglobin with Fe3+ called?

A

Methaemoglobin

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2
Q

What type of enzyme are P450?

A

Monoxygenase

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2
Q

How does a bruise appear after 5-10 days?

A

Greenish/yellowish - due to biliverdin

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2
Q

What makes conjugated bilirubin soluble?

A

Hydrophilic glucuronate

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3
Q

What is the implications of substances inducing its P450?

A

Can lead to the development of resistance to the drug or

Some people may be poor metabolises of a drug

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3
Q

How does a bruise appear after 1-2 days?

A

Bluish-purple/blackish

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3
Q

How can you treat Crigler-Najjar syndrome?

A

Fluorescent light therapy

Liver transplant

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3
Q

What is the major colourant of faeces?

A

Stercobilin

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4
Q

How does a bruise appear after 10-14 days?

A

Yellow-brown or light brown (bilirubin)

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6
Q

How do mitochondria appear when centrifuged?

A

A straw to red colour

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6
Q

What is special about CYP2D6?

A

It metabolising aprox. one quarter of all pharmaceuticals

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6
Q

What is the function of the mononuclear phagocyte system?

A

Destruction of old RBCs and WBCs

Formation of plasma proteins

Formation of antibody

Formation of bile pigment

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7
Q

What are the implications of low hemopexin?

A

Haemolytic anaemia

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8
Q

In general, how do cytochromes carry O2?

A

Fe2+ <> Fe3+

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10
Q

How are different P450 systems named?

A

CYP [number][letter][number]

CYP means cytochrome P450

And the latter are for family, subfamily and form respectively

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11
Q

How is urobilinogen made?

A

By the action of commensals in the gut

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13
Q

Which disease is aflatoxin associated with?

A

Kwashiorkor

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13
Q

What percentage of RBC turn over occurs outside the spleen?

A

10%

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14
Q

What does haem oxygenase resemble?

A

Globin

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15
Q

How long due RBCs last in the blood stream?

A

120 days

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15
Q

What does haemolytic crisis result in?

A

Anaemia

Jaundice

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16
Q

What happens to benzopyrene?

A

Can either be inactivated and safely secreted or

Activated into a carcinogen

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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

Hugh's MD1 Abdominal (21 decks)

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