Alcohol metabolism & oxidative stress Flashcards
Where is alcohol metabolised?
Liver
What enzymes are used to metabolise alcohol and what are their products (2 things)?
- Alcohol dehydrogenase: acetylaldehyde
- Aldehyde dehydrogenase: acetate
Consequences of acetylaldehyde accumulation (5 things)
- “Hangover” feeling
- Excess NADH and acetyl~CoA
- Fatty liver
- Alcoholic cirrhosis
- Alcoholic hepatitis
What drug is taken to treat alcohol dependence and how does it work (3 things)?
- Disulfarim
- Inhibitor of aldehyde dehydrogenase
- Causes “hangover” feeling
Metabolic response to chronic alcohol consumption (2 things)
- Inadequate NAD+ for multiple pathways
- Increased acetyl~CoA leading to fatty liver
What is oxidative stress?
Free radicals acquiring electrons from other molecules, causing damage
Reactive oxygen species (4 things)
- Oxygen (biradical, not too serious)
- Superoxide (1 more e- than O2)
- H2O2 (not free radical directly)
- Hydroxyl radical (reacts with anything)
Reactive nitrogen species (2 things)
- Nitric oxide reacts with superoxide to form peroxynitrite
- Not a free radical but a powerful oxidant that can damage cells
2 types of ROS damage to DNA
- Modified base can lead to mispairing and mutation
- Reacts with sugar that can cause strand break & mutation on repair
ROS damage to proteins (3 things)
- Directly with backbone leading to degradation
- Can modify side chain
- Could be positive or could lead to degradation
ROS damage to lipids (4 things)
- 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
Endogenous sources of biological oxidants (7 things)
- ETC
- Peroxidases
- Nitric oxide synthases
- Lipoxygenases
- NADPH oxidases
- Xanthine oxidase
- Monoamine oxidase
Exogenous sources of biological oxidants (4 things)
- Radiation
- Pollutants
- Drugs (primaquine)
- Toxins (herbicide)
How is superoxide produced?
Electrons can escape ETC and react with dissolved O2
3 types of nitric oxide synthase
- Inducible NOS (high NO conc.s in phagocytes for direct toxic effect)
- Endothelial NOS (signalling)
- Neuronal NOS (signalling)
What does low levels of nitric oxide signal (3 things)?
- Vasodilation
- Neurotransmission
- S-Nitrosylation
What is a respiratory/oxidative burst (3 things)?
- Rapid production of superoxide and H2O2
- ROS and peroxynitrite destroy invading bacteria
- Catalysed by NADPH oxidase
Chronic granulomatous disease (2:5 things)
- Genetic defect in NADPH oxidase
- Susceptible to atypical infections, pneumonia, abscesses, impetigo & cellulitis
Superoxide dismutase- SOD (3 things)
- Converts superoxide to H2O2 & O2
- Primary defence as superoxide is string initiator of chain reactions
- 3 isoenzymes (Cu, Zn, Mn)
Catalase (3 things)
- Converts H2O2 to water & O2
- Protects against oxidative burst
- Widespread enzyme
Cellular defences- glutathione (5 things)
- 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
Vitamin E as an antioxidant
Protects against lipid peroxidation (donates H atom)
Vitamin C as an antioxidant
Regenerates reduced form of vitamin E
Free radical scavengers (4 things)
- Carotenoids
- Flavonoids
- Uric acid
- Melatonin
