Oxidative Stress And Alcohol Metabolism

Question 1

What % of alcohol is metabolised by liver and what % is excreted in breath and urine?

Answer 1

90% in liver, 10% in breath and liver

Question 2

What is recommendations for alcohol consumption?

Answer 2

14 units per week spread over at least 3 days

Question 3

how many g of alcohol in a unit and how many g eliminated per hour?

Answer 3

8 g in one unit, 7g excreted per hour

Question 4

How is ethanol converted to acetate for krebs cycle or fatty acid synthesis?

Answer 4

ethanol oxidised by alcohol dehydrogenase and NAD to acetaldehyde
acetaldehyde oxidised to acetate by aldehyde dehydrogenase

Question 5

What substance causes hangover symptoms ?

Answer 5

build up of acetaldehyde

Question 6

Name an inhibitor of aldehyde dehydrogenase and its use

Answer 6

disulfiram

treats alcohol dependance by making hangover less severe

Question 7

How does alcohol cause fatty liver disease?

Answer 7

• increased acetyl coA
• increased synthesis of fatty acid and ketone bodies
• acetaldehyde build up toxic to hepatocytes so some may die/ loose function
• this means lipoproteins cannot be synthesised
• liver is main centre of lipogenesis and less lipoproteins means less removal and so lipid accumulates leading to fatty liver

Question 8

How does the decrease in NAD+ from alcohol metabolism lead to lactic aciosis and gout?

Answer 8

• Not enough NAD+ for lactate conversion to pyruvate
• Lactate accumulates in blood (leads to lactic acidosis)
• Kidneys ability to excrete uric acid crystals reduced
• urate crystals accumulate in tissues (leads to gout)

Question 9

How does the decrease in NAD from alcohol metabolism lead to hypoglycaemia?

Answer 9

• Not enough NAD+ for glycerol (from triglycerides) metabolism
• Deficit in gluconeogenesis as glycerol needed as intermediate to get around irreversible steps
• less gluconeogenesis means less glucose production so hypoglycaemia

Question 10

What reactive nitrogen species (nitrogen free radicals) are there?

Answer 10

nitric oxide (NO+•), peroxynitrate (ONOO-)- not free radical but powerful oxidising agent

Question 11

How can ROS (reactive oxygen species) damage proteins?

Answer 11

• damage backbone and lead to fragmentation
• change or modifiy side chains to change amino acids
• disulphide bond formation when takes electrons away from cystenines

Question 12

How can ROS damage DNA?

Answer 12

• react with base and cause mispairing and mutation

- reacts with sugar nucleotides to cause strand break and mutation on repair

Question 13

What do ROS produce that can be measured in a cell as an indicator of oxidative damage?

Answer 13

8-oxo-dG

Question 14

State where and how free radicals can form from endogenous sources?

Answer 14

• ETC- electrons escape and react with O2 to form superoxide
• Nitiric oxide synthase- creates nitric oxide which is used normally for vasodilation and neurotransmission but toxic at high levels
• NADHP oxidase/ respiratory burst- H2O2 and superoxides, as well as ONOO- and NO are released to kill bacteria
• Peroxidases
• Monoamine oxidase

Question 15

State some exogenous sources of free radicals

Answer 15

• radiation
• pollutants
• drugs (primaquine- antimalarial)
• toxins (herbicides)

Question 16

How does superoxide dismutase work?

Answer 16

converts superoxide in to H202 and O2

Question 17

How does catalase work?

Answer 17

converts H202 to water and O2 (important in WBCs protection against respiratory burst)

Question 18

How does glutathione (GSH) work and what is it?

Answer 18

a tripeptide synthesised by body .
Thiol group of cys donates e- to radical, then reacts with another GSH, forming a disulphide bond and becoming GSSG with enzyme glutathione peroxidase and selenium cofactor. GSSG is converted back to GSH by glutathione reductase and NADPH

Question 19

State free radical scavengers that are non enzymatic

Answer 19

• Vit E, Vit C, flavenoids, uric acid, melatonin, carotenoids

Question 20

What happens to paracetamol at normal doses?

Answer 20

• converted to glucuronide and sulphate (safely excreted)

Question 21

What happens to paracetamol at over doses?

Answer 21

converted to NAPQI which causes oxidative damage to liver cells, damage to protein and DNA –> liver failure

Question 22

How is paraectamol overdose treated?

Answer 22

Acetyl cysteine, this replenished glutathione levels so protects from oxidative damage

Question 23

Which enzyme is important in producing the respiratory burst to fight infection?

Answer 23

NADPH oxidase