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MEH- Aboli > Alcohol metabolism & oxidative stress > Flashcards

Alcohol metabolism & oxidative stress Flashcards

1
Q

Where is alcohol metabolised?

A

Liver

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2
Q

What enzymes are used to metabolise alcohol and what are their products (2 things)?

A
  • Alcohol dehydrogenase: acetylaldehyde
  • Aldehyde dehydrogenase: acetate
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3
Q

Consequences of acetylaldehyde accumulation (5 things)

A
  • “Hangover” feeling
  • Excess NADH and acetyl~CoA
  • Fatty liver
  • Alcoholic cirrhosis
  • Alcoholic hepatitis
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4
Q

What drug is taken to treat alcohol dependence and how does it work (3 things)?

A
  • Disulfarim
  • Inhibitor of aldehyde dehydrogenase
  • Causes “hangover” feeling
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5
Q

Metabolic response to chronic alcohol consumption (2 things)

A
  • Inadequate NAD+ for multiple pathways
  • Increased acetyl~CoA leading to fatty liver
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6
Q

What is oxidative stress?

A

Free radicals acquiring electrons from other molecules, causing damage

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7
Q

Reactive oxygen species (4 things)

A
  • Oxygen (biradical, not too serious)
  • Superoxide (1 more e- than O2)
  • H2O2 (not free radical directly)
  • Hydroxyl radical (reacts with anything)
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8
Q

Reactive nitrogen species (2 things)

A
  • Nitric oxide reacts with superoxide to form peroxynitrite
  • Not a free radical but a powerful oxidant that can damage cells
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9
Q

2 types of ROS damage to DNA

A
  • Modified base can lead to mispairing and mutation
  • Reacts with sugar that can cause strand break & mutation on repair
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10
Q

ROS damage to proteins (3 things)

A
  • Directly with backbone leading to degradation
  • Can modify side chain
  • Could be positive or could lead to degradation
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11
Q

ROS damage to lipids (4 things)

A
  • H atom extracted from tail
  • Lipid radical formed which reacts with O2 to form lipid peroxy radical
  • Chain reaction
  • Hydrophobic environment disrupted and membrane integrity fails
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12
Q

Endogenous sources of biological oxidants (7 things)

A
  • ETC
  • Peroxidases
  • Nitric oxide synthases
  • Lipoxygenases
  • NADPH oxidases
  • Xanthine oxidase
  • Monoamine oxidase
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13
Q

Exogenous sources of biological oxidants (4 things)

A
  • Radiation
  • Pollutants
  • Drugs (primaquine)
  • Toxins (herbicide)
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14
Q

How is superoxide produced?

A

Electrons can escape ETC and react with dissolved O2

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15
Q

3 types of nitric oxide synthase

A
  • Inducible NOS (high NO conc.s in phagocytes for direct toxic effect)
  • Endothelial NOS (signalling)
  • Neuronal NOS (signalling)
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16
Q

What does low levels of nitric oxide signal (3 things)?

A
  • Vasodilation
  • Neurotransmission
  • S-Nitrosylation
17
Q

What is a respiratory/oxidative burst (3 things)?

A
  • Rapid production of superoxide and H2O2
  • ROS and peroxynitrite destroy invading bacteria
  • Catalysed by NADPH oxidase
18
Q

Chronic granulomatous disease (2:5 things)

A
  • Genetic defect in NADPH oxidase
  • Susceptible to atypical infections, pneumonia, abscesses, impetigo & cellulitis
19
Q

Superoxide dismutase- SOD (3 things)

A
  • Converts superoxide to H2O2 & O2
  • Primary defence as superoxide is string initiator of chain reactions
  • 3 isoenzymes (Cu, Zn, Mn)
20
Q

Catalase (3 things)

A
  • Converts H2O2 to water & O2
  • Protects against oxidative burst
  • Widespread enzyme
21
Q

Cellular defences- glutathione (5 things)

A
  • Protects against oxidative damage
  • GSH reacts with another GSH to form GSSG (Disulphide)
  • Glutathione peroxidase needs Se
  • GSSG reduced back to GSH by glutathione reductase
  • It catalyses transfer of e- from NADPH
22
Q

Vitamin E as an antioxidant

A

Protects against lipid peroxidation (donates H atom)

23
Q

Vitamin C as an antioxidant

A

Regenerates reduced form of vitamin E

24
Q

Free radical scavengers (4 things)

A
  • Carotenoids
  • Flavonoids
  • Uric acid
  • Melatonin
25
Q

What are Heinz bodies (2 things)?

A
  • Dark staining within RBC resulting from precipitating Hb
  • Bind to cell membrane altering rigidity
26
Q

How does acetylcysteine treat paracetamol overdose?

A

Replenishes GSH levels to prevent oxidative damage

MEH- Aboli (6 decks)

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