Oxidative Stress And Alcohol Metabolism

Question 1

What is alcohol oxidised by and to what?

Answer 1

Alcohol to acetaldehyde by alcohol dehydrogenase.
Acetaldehyde to acetate by aldehyde dehydrogenase.
Acetate to acetyl CoA.

Question 2

What can smaller amounts of alcohol be oxidised by?

Answer 2

Cytochrome P450 2E1 enzyme (CYP2E1) and catalase in brain

Question 3

What are the toxic effects of alcohol in the liver?

Answer 3

Using up NAD+ and accumulation of acetaldehyde.

Excess of NADH and acetyl CoA leads to change in liver metabolism.

Question 4

Treatment for alcohol dependence and mechanism

Answer 4

Disulfiram. Inhibitor of aldehyde dehydrogenase. Results in accumulation of acetaldehyde, causing symptoms of a hangover.

Question 5

Reactive nitrogen species

Answer 5

Nitric oxide –> peroxynitrite

NO* –> ONOO-

Question 6

Reactive oxygen species

Answer 6

Superoxide –> hydrogen peroxide –> hydroxyl radical

O2- –> H2O2 –> OH

Question 7

What can be used as a measurement of oxidative damage in cells?

Answer 7

Amount of 8-oxo-dG.

Oxidative stress and alcohol metabolism lecture slide 13

Question 8

Where are disulfide bonds formed and as a result of what?

Answer 8

Between thiol groups of cysteine.

ROS

Question 9

ROS damage to lipids

Answer 9

Free radical extracts hydrogen atom from a polyunsaturated fatty acid. Lipid peroxyl radical formed after reaction with oxygen.

Question 10

Endogenous sourced of biological oxidants

Answer 10

Electron transport chain, nitric oxide synthase, NADPH oxidases

Question 11

What are the three types of nitric oxide synthase?

Answer 11

iNOS - inducible nitric oxide synthase. Produces high NO concentrations in phagocytes for direct toxic effect.
eNOS - endothelial nitric oxide synthase (signalling)
nNOS - neuronal nitric oxide synthase (signalling)

Question 12

What is a respiratory burst?

Answer 12

Rapid release of superoxide and H2O2 from phagocytic cells. Uses NADPH oxidase. Peroxynitrite also used to destroy invading bacteria.

Question 13

Cellular defences against ROS

Answer 13

Superoxide dismutase, catalase, glutathione

Question 14

Superoxide dismutase and catalase

Answer 14

1) Superoxide –> H2O2 + O2

2) H2O2 –> H2O + O2

Question 15

Glutathione (GSH) role in protection against ROS

Answer 15

2GSH –> GSSG catalysed by glutathione peroxidase (requires selenium).
Reduced back to GSH by glutathione reductase (catalysed transfer of e- from NADPH to disulphide bonds).

Question 16

What is produced in the pentose phosphate pathway? What is its rate limiting enzyme?

Answer 16

NADPH, ribose 5-phosphate, CO2.

Glucose 6-phosphate dehydrogenase.

Question 17

Free radical scavengers (vitamins)

Answer 17

Vitamin E - lipid soluble, protection against lipid peroxidation.
Vitamin C - water soluble, important role in regenerating reduced form of Vitamin E.

Question 18

Enzyme deficiencies in Galactosaemia

Answer 18

Galactokinase, UDP-galactose epimerase, uridyl transferase

Question 19

Symptoms of Galactosaemia

Answer 19

Hepatomegaly and Cirrhosis
Renal failure
Vomiting
Seizure and Brain damage
Cataracts
Hypoglycaemia

Question 20

Heinz bodies

Answer 20

Precipitated haemoglobin. Bind to cell membrane, altering rigidity. Increased mechanical stress when cells squeeze through capillaries. Clinical sign of G6PDH deficiency.

Question 21

Normal metabolism if paracetamol

Answer 21

Conjugation with glucuronide or sulphate

Question 22

Paracetamol metabolism: toxic metabolite

Answer 22

NAPQI (N-acetyl-p-benzo-quinone imine).

Causes oxidative damage to liver and depletes stores of glutathione.

Question 23

Paracetamol metabolism: treatment

Answer 23

Acetylcysteine, precursor for glutathione