Alcohol Metabolism

Question 1

Where is most of alcohol metabolised?

Answer 1

The liver

Question 2

What happens to the alcohol that is not metabolised?

Answer 2

Excreted in urine and breath

Question 3

What oxidises alcohol?
Into what?

Answer 3

Alcohol dehydrogenase
Acetaldehyde

Question 4

What oxidises acetaldehyde?
Into what?

Answer 4

Aldehyde dehydrogenase
Acetate

Question 5

What is acetate converted into?

Answer 5

Acetyl CoA

Question 6

What is acetyl CoA used in? (2)

Answer 6

TCA cycle
Fatty acid synthesis

Question 7

If alcohol isn’t oxidised by alcohol dehydrogenase what can it be oxidised by?

Answer 7

Catalase in the brain
Cytochrome P450 2E1

Question 8

What is the recommended alcohol consumption?

Answer 8

14 units
Spread over at least three days

Question 9

What is the rate of alcohol elimination?

Answer 9

7g per hour

Question 10

How many grams is one unit of alcohol?

Answer 10

8g

Question 11

What causes a hangover as well as dehydration?

Answer 11

Accumulation of acetaldehyde - which is toxic

Question 12

What enzyme controls the levels of acetaldehyde?
How?

Answer 12

Aldehyde dehydrogenase
Has a low Km for acetaldehyde - high affinity

Question 13

What is the primary cause of liver damage?

Answer 13

Prolonged and excessive alcohol consumption
Acetaldehyde accumulation

Question 14

What causes changes in liver metabolism?

Answer 14

Excess NADH
Excess Acetyl CoA

Question 15

Three key conditions that effect the liver, caused by excessive alcohol consumption

Answer 15

Fatty liver
Alcohol hepatitis - inflammation of the liver
Alcohol cirrhosis - the liver has become significantly scarred

Question 16

What drug is used in the treatment of alcohol dependence?

Answer 16

Disulfiram

Question 17

How does disulfiram work?

Answer 17

Inhibits aldehyde dehydrogenase
Acetaldehyde accumulates if alcohol drunk - causing nausea

Question 18

Explain how increased NADH effects liver metabolism (3)

Answer 18

1. NAD+ levels inadequate for fatty acid oxidation
2. Less lactate converted to pyruvate
3. Lactate accumulate in the blood

Question 19

How is the electron transport chain a source of ROS?

Answer 19

E- can escape the chain and react with dissolved O2
To form superoxide

Question 20

What are the three types of NOS?
What do they all do?

Answer 20

INOS - inducible - produces high NO conc in phagocytes for direct toxic effect
ENOS - endothelial - signalling
NNOS - neuronal - signalling

Question 21

What is NOS?

Answer 21

Nitric oxide synthase

Question 22

Toxicity of NO* (nitric oxide)

Answer 22

Toxic at high levels

Question 23

Role of NO* (2)

Answer 23

Vasodilation
Neurotransmission

Question 24

What occurs in respiratory burst? (2)

Answer 24

1. Rapid production of superoxide and H2O2 - from phagocytic cells
2. The bacteria around the cell are destroyed (sometimes the phagocytic cells are too)

Question 25

What enzyme is required in respiratory burst? Where is it found? What does it do?

Answer 25

NADPH oxidase Present in membrane of phagosomes Transfers e- from NADPH to O2 - to make superoxide radicals

Question 26

Link defect in respiratory burst process to a disease

Answer 26

Genetic defect in NADPH oxidase Enhanced susceptibility to bacterial infects (Pneumonia, abscesses…)

Question 27

What are two enzymes in cellular defence against ROS and RNS

Answer 27

Superoxide dismutase Catalase

Question 28

How does superoxide dismutase work?

Answer 28

Converts superoxide (O2*-) to H2O2 and O2

Question 29

How does catalase work (in defences against oxidative stress)? What type of cells are they prominent in?

Answer 29

Converts H2O2 to H2O and O2 Immune cells

Question 30

What is another cellular defence of a cellular defence?

Answer 30

Glutathione (GSH)

Question 31

How does glutathione act as a cellular defence?

Answer 31

The structure is GLY-CYS-GLU The thiol group of Cys donates e- to ROS + reacts with another GSH to form a disulphide bond - now GSSG

Question 32

What enzyme is required in the bonding of two Cys molecules during glutathione cellular defence? What does it require?

Answer 32

Glutathione peroxidase Selenium

Question 33

What is required to reduce GSSG back to GSH? How does it work?

Answer 33

Glutathione reductase Catalyses the transfer of e- from NADPH to disulphide bond of GSSG Resulting in GSH

Question 34

What is the main source of NADPH?

Answer 34

Pentose phosphate pathway

Question 35

Name two free radical scavengers Name their solubilities Where they are important

Answer 35

Vitamin E - lipid soluble, protection against lipid peroxidation Vitamin C - water soluble, regenerate reduced form of vitamin E!

Question 36

How do free radical scavengers work?

Answer 36

Reduce free radical damage Donate H atom and its electron to free radicals in non enzymatic reactions

Question 37

Name the ROS and RNS

Answer 37

O2*- superoxide H2O2 hydrogen peroxide *OH hydroxyl radical NO* nitric oxide ONOO- peroxynitrite

Question 38

How do Heinz bodies form?

Answer 38

G6PDH deficiency Less NADPH produced in Pentose phosphate pathway Less GSH reformed Haemolysis - cross linked haemoglobin form Heinz bodies

Question 39

What is a clinical sign of G6PDH deficiency?

Answer 39

Heinz bodies

Question 40

What do Heinz bodies do?

Answer 40

Bind to membrane Altering structure of RBC RBC can’t fit through small capillaries

Question 41

How do anti-malarials effect ROS?

Answer 41

Deplete NADPH GSH not reformed

Question 42

Why are RBC more susceptible to oxidative stress?

Answer 42

In RBC the only way of getting NADPH is through pentose phosphate pathway

Question 43

What can small amounts of alcohol be metabolised by?

Answer 43

P450 enzymes Catalase in the brain

Question 44

What is the rate of alcohol metabolism?

Answer 44

7g/hr

Question 45

What processes would increase in chronic excessive alcohol consumption?

Answer 45

Synthesis of fatty acids and ketone bodies