Detoxification Pathways in the Liver Flashcards

1
Q

How are dietary toxins directed to the liver?

A

Via the portal vein

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2
Q

What size chemicals does the cytochrome P450 system oxidise?

A

Mr < 5000 - bigger than this will be dealt by the immune system

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3
Q

What is the nomenclature for cytochrome P450?

A

CYP family, subfamily, form e.g. CYP2A6

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4
Q

Where are cytochrome P450 located in vivo?

A

in endoplasmic reticulum and mitochondria

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5
Q

Where are cytochrome P450 located in vitro?

A

microsomes

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6
Q

Why is the cytochrome P450 called 450?

A

Because that is the maximum absorbance when bound with carbon monoxide

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7
Q

What is the role of all cytochromes?

A

To carry electrons involving Fe2+ > Fe3+

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8
Q

What is the role of cytochrome P450 in the liver?

A

to alter molecules to a soluble form so they can be excreted by the kidneys

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9
Q

What type of enzyme is cytochrome P450?

A

a monooxygenase - adds an OH group to the molecule

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10
Q

What reaction does cytochrome P450 catalyse?

A

formula – won’t paste from Evernote

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11
Q

What is the major reaction of cytochrome P450?

A

hydroxylation

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12
Q

What is epoxidation?

A

A reaction that can be done by P450 which results in a substrate that is highly reactive with DNA

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13
Q

Does the substrate just undergo one reaction?

A

No - can undergo multiple sequential reactions

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14
Q

How is the cytochrome P450 reaction initiated?

A

By the binding of a substrate to P450

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15
Q

What is the function of the reductase also present in the membrane?

A

To pass one electron at a time to cytochrome P450

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16
Q

How is a reactive oxygen species sometimes formed?

A

If the electrons which are passed as peroxide don’t hit the substrate

17
Q

What is the active site in each P450 specific for?

A

a class of substrates that it will hydroxylate - all others will be be oxygenated

18
Q

How does cytochrome P450 connect to the ER?

A

a hydrophobic foot

19
Q

What part of the cytorchome P450 protein forms a ligand to the Fe in haem?

A

a cysteine anchor

20
Q

How does the liver become tolerant to certain toxins?

A

higher levels of certain P450s are expressed when substrates are persistently present - either by activating the gene, stabilising the mRNA or by protecting it from turnover

21
Q

How many genes for P450 are there in humans?

A

57

22
Q

What is the outcome of inherited deficiencies in certain P450s?

A

poor metabolism of certain drugs

23
Q

What is the result of a deficiency in CYP2D6?

A

failure to covert codeine to morphine

24
Q

What is benzpyrene?

A

an inactive combustion product in smoke which can be converted to a carcinogen by P450

25
Q

What is the Ames test?

A

A test to determine if a substrate is mutagenic with the action of P450

26
Q

What is aflatoxin?

A

a substrate which can be made carcinogenic by P450 and contributes to the severity of kwashiorkor

27
Q

What is dioxin?

A

a substrate in agent orange which activates the gene CYP1A1