Alcohol Metabolism And Oxidative Stress (S3L1)

Question 1

Where is 90% of alcohol metabolised?

Answer 1

Liver

Question 2

Alcohol is converted to acetaldehyde by what enzyme?

Answer 2

Alcohol dehydrogenase

Question 3

Acetaldehyde is converted to acetate by what enzyme?

Answer 3

Aldehyde dehydrogenase

Question 4

What is the recommended limit of alcohol per week?

Answer 4

14 units for men and women spread over 3 days

Question 5

What is acetate converted to in the liver?

Answer 5

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

Question 6

Acetaldehyde is a toxic metabolite. Accumulation causes what?

Answer 6

Hangover

Question 7

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

Answer 7

Low

Question 8

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

Answer 8

Fatty liver, alcoholic hepatitis, alcoholic cirrhosis

Question 9

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

Answer 9

Decrease

Question 10

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

Answer 10

Disulfiram (it inhibits aldehyde dehydrogenase)

Question 11

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

Answer 11

Lactic acidosis

Question 12

What are free radicals?

Answer 12

An atom or molecule that contains one or more unpaired electrons

Question 13

Give some examples of Reactive Oxygen Species

Answer 13

Superoxide, hydrogen peroxide, hydroxyl radical (most damaging)

Question 14

Give some examples of Reactive Nitrogen Species

Answer 14

Nitric oxide, peroxynitrite (ONOO-)

Question 15

Which 3 groups do ROS damage?

Answer 15

DNA, proteins, lipids

Question 16

How do ROS damage proteins?

Answer 16

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

Question 17

Give some sources of endogenous oxidants

Answer 17

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

Question 18

Give some examples of exogenous oxidants

Answer 18

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

Question 19

How is the electron transport chain a source of ROS?

Answer 19

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

Question 20

What is iNOS?

Answer 20

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

Question 21

Summarise the ‘respiratory burst’ that occurs within phagocytes

Answer 21

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

Question 22

What is chronic granulomatous disease?

Answer 22

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

Question 23

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

Answer 23

Superoxide dismutase (SOD), Catalase and Glutathione

Question 24

What does SOD do?

Answer 24

Converts superoxide to hydrogen peroxide and oxygen

Question 25

What does catalase do?

Answer 25

Converts hydrogen peroxide to water and O2

Question 26

Glutathione forms a disulphide bond with what?

Answer 26

Another glutathione molecule

Question 27

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

Answer 27

An electron is donated to ROS

Question 28

The enzyme glutathione peroxidase requires what to function?

Answer 28

Selenium

Question 29

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

Answer 29

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

Question 30

What are the free rad scavengers?

Answer 30

Vitamin E and C

Question 31

Galactosaemia favours the conversion of galactose to what?

Answer 31

Galactitol

Question 32

Galactosaemia is a deficiency in what?

Answer 32

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

Question 33

The conversion of galactose to galactitol uses up...?

Answer 33

NADPH - therefore greater potential for ROS damage

Question 34

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

Answer 34

Cataracts

Question 35

What is the clinical sign of G6PDH deficiency?

Answer 35

Aggregates of cross linked Hb - Heinz bodies

Question 36

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

Answer 36

NAPQI

Question 37

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

Answer 37

Acetylcysteine (replenishes glutathione)