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Metabolism, Endocrinology and Haematology > Alcohol Metabolism And Oxidative Stress (S3L1) > Flashcards

Alcohol Metabolism And Oxidative Stress (S3L1) Flashcards

1
Q

Where is 90% of alcohol metabolised?

A

Liver

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2
Q

Alcohol is converted to acetaldehyde by what enzyme?

A

Alcohol dehydrogenase

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3
Q

Acetaldehyde is converted to acetate by what enzyme?

A

Aldehyde dehydrogenase

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4
Q

What is the recommended limit of alcohol per week?

A

14 units for men and women spread over 3 days

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5
Q

What is acetate converted to in the liver?

A

Acetyl CoA (which can enter TCA cycle or be used for fatty acid synthesis)

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6
Q

Acetaldehyde is a toxic metabolite. Accumulation causes what?

A

Hangover

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7
Q

Does aldehyde dehydrogenase have a low or high Km for acetaldehyde?

A

Low

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8
Q

Excess NADH and acetyl CoA production causes changes to liver metabolism. Give 3 damaging signs

A

Fatty liver, alcoholic hepatitis, alcoholic cirrhosis

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9
Q

Does chronic alcohol consumption decrease or increase the NAD+/NADH ratio?

A

Decrease

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10
Q

What is the name of the drug that can be used in the treatment of chronic alcohol dependence?

A

Disulfiram (it inhibits aldehyde dehydrogenase)

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11
Q

Alcohol oxidation reduces levels of NAD+ . As a result lactate cannot be converted to pyruvate. What can this lead to?

A

Lactic acidosis

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12
Q

What are free radicals?

A

An atom or molecule that contains one or more unpaired electrons

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13
Q

Give some examples of Reactive Oxygen Species

A

Superoxide, hydrogen peroxide, hydroxyl radical (most damaging)

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14
Q

Give some examples of Reactive Nitrogen Species

A

Nitric oxide, peroxynitrite (ONOO-)

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15
Q

Which 3 groups do ROS damage?

A

DNA, proteins, lipids

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16
Q

How do ROS damage proteins?

A

They can either cause fragmentation to backbone or modify side chains resulting in a change in protein structure and consequently function

17
Q

Give some sources of endogenous oxidants

A

Electron transport chain, nitric oxide synthases, NADPH oxidises, peroxidases

18
Q

Give some examples of exogenous oxidants

A

Radiation (X-ray, UV, cosmic rays), pollutants, drugs (Primaquine - antimalarial), toxins (herbicide)

19
Q

How is the electron transport chain a source of ROS?

A

Oxygen is used in the ETC to receive electrons and produce water. Stray electrons can react with oxygen to produce superoxide radical

20
Q

What is iNOS?

A

Inducible nitric oxide synthase - produces high NO concentrations in phagocytes for direct toxic effect

21
Q

Summarise the ‘respiratory burst’ that occurs within phagocytes

A
  • Rapid release of superoxide and hydrogen peroxide from phagocytes
  • ROS and peroxynitrite destroy invading bacteria
  • Part of antimicrobial defence system
22
Q

What is chronic granulomatous disease?

A

Genetic defect in NADPH oxidase complex, thus enhancing susceptibility to bacterial infections

23
Q

What are the 3 main cellular defences against ROS and RNS?

A

Superoxide dismutase (SOD), Catalase and Glutathione

24
Q

What does SOD do?

A

Converts superoxide to hydrogen peroxide and oxygen

25
Q

What does catalase do?

A

Converts hydrogen peroxide to water and O2

26
Q

Glutathione forms a disulphide bond with what?

A

Another glutathione molecule

27
Q

When glutathione forms a double bond with another glutathione molecule, what is donated in the process?

A

An electron is donated to ROS

28
Q

The enzyme glutathione peroxidase requires what to function?

A

Selenium

29
Q

Glutathione is regenerated by glutathione reductase - what is needed to facilitate this reaction?

A

NADPH - this is a reason why the pentose pathway is important (pentose p produces NADPH)

30
Q

What are the free rad scavengers?

A

Vitamin E and C

31
Q

Galactosaemia favours the conversion of galactose to what?

A

Galactitol

32
Q

Galactosaemia is a deficiency in what?

A

3 enzymes - galactokinase, UDP- galactose epimerase, uridyl transferase

33
Q

The conversion of galactose to galactitol uses up…?

A

NADPH - therefore greater potential for ROS damage

34
Q

Crystallin protein in the lens of the eye is particularly susceptible to ROS damage. What can this damage cause?

A

Cataracts

35
Q

What is the clinical sign of G6PDH deficiency?

A

Aggregates of cross linked Hb - Heinz bodies

36
Q

What is the toxic metabolite formed as a result of paracetamol overdose?

A

NAPQI

37
Q

What treatment should be given in the case of paracetamol overdose?

A

Acetylcysteine (replenishes glutathione)

Metabolism, Endocrinology and Haematology (7 decks)

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