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MEH > Alcohol Metabolism And Oxidative Stress > Flashcards

Alcohol Metabolism And Oxidative Stress Flashcards

1
Q

Site of alcohol metabolism

A

Liver

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2
Q

How is alcohol excreted

A

Urine
Passively on the breath
Oxidised by cytochrome P450 2E1 enzyme or catalase in the brain

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3
Q

Recommended units of alcohol per week

A

14

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4
Q

1 unit = how much ethanol

A

10ml (8g)

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5
Q

Elimination rate of alcohol

A

7g per hour

Zero order kinetics

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6
Q

Enzyme converting alcohol to acetaldehyde

A

Alcohol dehydrogenase

Reducing NAD+ to NADH

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7
Q

Enzyme oxidising acetaldehyde to acetate

A

Aldehyde dehydrogenase
NAD+ reduced to NADH

Very low Km

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8
Q

Effects of prolonged excessive alcohol consumption

A

Fatty liver
Alcoholic cirrhosis
Alcoholic hepatitis

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9
Q

Effects of decrease in NAD+/NADH ratio

A
  • reduced conversion of lactate to Pyruvate - lactic acidosis and gout
  • reduced glycerol metabolism - decreased gluconeogenesis - hypoglycaemia
  • reduced beta oxidation of fatty acids
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10
Q

Effects of increase in acetyl coenzyme A

A
  • fatty acid accumulation causing fatty liver as lack of lipoprotein synthesis
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11
Q

Damaged liver cells

A
  • leaky plasma membrane - transaminase and gamma glutamyl transpeptidase in blood (marker)
  • reduced uptake and conjugation of bilirubin - jaundice
  • reduced urea production - hyperammoneamia
  • reduced protein synthesis - low serum albumin, clotting factors and lipoproteins
  • low albumin - oedema
  • low CF - increased prothrombin time
  • low lipoproteins - fatty liver
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12
Q

Direct effects of alcohol on GI

A

Damage cells lining the GI

Diarrhoea
Loss of appetite
Less absorption of nutrients e.g vitamin K
Thiamine - neurological symptoms - wernicke’s Korsakoff syndrome
Folic acid - macrocytic anaemia

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13
Q

Direct damage to pancreas

A

Chronic pancreatitis

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14
Q

Treatment

A

Disulfiram used as adjunct
Inhibits aldehyde dehydrogenase
accumulation of acetaldehyde - hangover symptoms

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15
Q

Free radicals

A

Species with an unpaired electron that can exist independently
Very reactive
Causes damage to cells
Can propagate further radicals causing a chain reaction of damage

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16
Q

Reactive oxygen species

A

Oxygen — superoxide (O2-) — hydrogen peroxide (H2O2) —hydroxyl radical (OH) and water — water

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17
Q

Hydroxyl radical

A

Most reactive and damaging free radical

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18
Q

Hydrogen peroxide

A

Not free radical but can react with Fe2+ to produce free radical

19
Q

Biradical

A

2 unpaired electrons in different orbitals with different spins
Eg molecular oxygen

20
Q

Sources of biological oxidants

A

Exogenous
Ionising Radiation
Toxins - herbicide eg Paraquat produces superoxide

21
Q

Reactive nitrogen species

A

Superoxide (O2-) + nitric oxide (NO) —> peroxynitrite (ONOO-)

22
Q

Types of damage by ROS

A

DNA
Proteins
Lipids

23
Q

DNA damage by ROS

A

Reacts with base - mismatch mutation
Reacts with sugar - double strand break - mutation on repair

Cancer

Amount of 8-oxo-dG used as a marker for oxidative damage

24
Q

ROS damage to proteins

A

React with protein backbone - fragmentation - degredation

React with side chains - modified amino acid - change in structure, function

25
Q

Heinz bodies

A

ROS stakes an electron from cysteine
Think group more reactive
Inappropriate Disulfide bonds formed
Misfolding and cross linking

Heinz bodies accumulate - precipitated cross linked Hb

26
Q

Lipid peroxidation

A
  1. Free radical extracts electron from a polyunsaturated FA
  2. Lipid radical formed
  3. Reacts with oxygen to form lipid peroxyl radical
  4. Chain reaction as lipid peroxyl radical reacts with another FA

Hydrophobic environment disrupted in membrane bilayer - reduced integrity

27
Q

Endogenous sources of oxidants

A 
Electron transport chain 
Nitric oxide syntheses 
NADPH oxidases - produces superoxide (resp burst)
Peroxidases 
Lipoxygenases
28
Q

Nitric oxide syntheses

A

Inducible NO synthase - phagocytes direct toxic effect
Endothelial NO synthase - vasodilator
Neuronal NO synthase - signalling

29
Q

NO synthesis

A

Arginine —> citruline + NO*

Using nitric oxide synthase
NADPH oxidised to NADP

30
Q

Respiratory burst

A
  1. Phagosome uses NADPH oxidase in cell membrane to convert NADPH to NADP and donate electron to oxygen to form superoxide
  2. Phagosome engulfs bacteria
  3. Superoxide converted to hydrogen peroxide
  4. Secretory granules containing myeloperoxidase converts hydrogen peroxide to hypochlorite HOCl* which destroys bacteria
31
Q

Galactosaemia

A

Increased activity of aldose reductase uses up NADPH
Less NADPH available for GSSG therefore glutathione recycled less
More susceptible to oxidative damage

32
Q

Glucose 6 phosphate deficiency

A

Deficiency in G6P dehydrogenase in pentode phosphate pathway
Produce less NADPH
Less glutathione recycled
More susceptible to oxidative damage

33
Q

Cellular defences against free radicals - antioxidants

A 
Superoxide dismutase
Glutathione 
Vitamin C and E 
Carotenoids, melatonin, uric acid, flavonoids 
Catalase
34
Q

Superoxide dismutase

A

Converts superoxide to hydrogen peroxide, oxygen and water

35
Q

Catalase

A

Hydrogen peroxide to water and oxygen

In immune cells to protect against respiratory burst

36
Q

Glutathione

A

Glycine - cysteine - glutamate

Reduced form - SH
Oxidated form - GSSG

  1. Thiol group donates electron to ROS
  2. GSH reacts with another GSH to form GSSG using glutathione peroxidase
  • requires selenium

Glutathione reductase converts GSSG back to 2 x GSH using NADPH

37
Q

Vitamin E

A

Free radical scavenger
Reduces lipid radicals by donating an electron
Protects against lipid peroxidation

38
Q

Vitamin C

A

Regenerates Vitamin E reduced form

39
Q

Causes of oxidative stress

A

Infection
Anti malaria drugs
Broad beans

40
Q

Effects of oxidative stress

A

Lipid peroxidation - loss of cell membrane integrity - deformed
Heinz bodies - haemolysis

41
Q

Metabolism of paracetamol at prescribed dosage

A

Metabolised in the liver by conjugation with glucuronide or sulphate

42
Q

Overdose of paracetamol (10g)

A

Converted to NAPQI oxidising agent
Toxic to hepatocytes
- conjugates with glutathione - less available antioxidant
- covalent binding in hepatic proteins

43
Q

Treatment of paracetamol overdose

A

Acetylcysteine - replenish glutathione

MEH (3 decks)

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