Alcohol metabolism

Question 1

Describe how alcohol is metabolised

Answer 1

alcohol oxidised by alcohol dehydrogenase to acetaldehyde

• then to acetate by aldehyde dehydrogenase
  - (both reducing NAD+ to NADH)
  • acetate conjugated to coenzyme A to form acetyl coA

smaller amounts of alcohol can be oxidised by cytochrome P450 2E1 enzyme (CYP2E1) or catalase in brain

Question 2

What keeps alcohol toxicity to a minimum

Answer 2

toxicity kept to minimum by aldehyde dehydrogenase
- low Km for acetaldehyde

Question 3

Lactic acidosis

Answer 3

decreased NAD+/NADH

- inadequate NAD+ for conversion of lactate to pyruvate

    - lactate accumulates in blood

        - kidney’s ability to excrete uric acid reduced as same transporter is used

            - urate crystals accumulate in tissues producing gout

Question 4

Hypoglycaemia

Answer 4

decrease in NAD+/NADH
- inadequate NAD+ for glycerol metabolism
- + lactate accumulation in blood
- deficit in gluconeogenesis

Question 5

Fatty liver

Answer 5

decrease in NAD+/NADH
- inadequate NAD+ for fatty acid oxidation

increased acetyl coA
- increased synthesis of fatty acids & ketone bodies
- +alongside: increased synthesis of TAG
- with lower lipoprotein synthesis

Question 6

• Explain the mechanism of action of Disulfiram

Answer 6

adjunct in treatment of chronic alcohol dependence

- inhibitor of aldehyde dehydrogenase

    - acetaldehyde (nausea) would accumulate

        - cause symptoms of hangover