Alcohol metabolism and oxidative stress Flashcards
How is alcohol metabolised?
Oxidised to acetaldehyde (toxic metabolite causes hangover feeling) by alcohol dehydrogenase and then to acetate by aldehyde dehydrogenase. Then acetate converted into acetyl-coA to be used in TCA cycle.
What is the recommended alcohol limits?
No more than 14 units of alcohol a spread spread over at least 3 days
What is the average rate of alcohol metabolism?
1 unit of alcohol = 8g
Eliminated at 7g per hour
How can prolonged/excessive alcohol consumption cause liver damage?
An accumulation of acetaldehyde which is normally controlled by aldehyde dehydrogenase enzyme.
The excess of NADH and acety-CoA produced change liver metabolism pathways e.g. cause cirrhosis or hepatitis.
Decreased NAD+/NADH ratio leads to to not enough NAD+ for lactate to pyruvate metabolism, for glycerol metabolism and fatty acid oxidation. Lactate can build up in blood, hypoglycaemia from deficit in gluconeogenesis.
Increased acetyl-CoA leads to increased FA and ketone bodies leading to increased TAG synthesis and fatty liver because of lower lipoprotein synthesis to carry fats away from liver.
What is disulfiram?
An inhibitor of the enzyme aldehyde dehydrogenase so acetaldehyde builds up and this causes symptoms of a hangover so patients associate alcohol with feeling very unwell.
What is oxidative stress?
When cellular damage by ROS and RNS outweighs cell defences e.g. antioxidants.
What are the examples of ROS and RNS?
Oxygen - biradical
Superoxide 02*
Hydrogen peroxide H2O2 - reacts with FE2+ to produce free radicals
Hydroxyl radical OH* - most damaging, very reactive
Nitric oxide - NO*
Peroxynitrite ONOO- powerful oxidant but not free radical
Explain how ROS can damage DNA?
ROS reacts with a base to lead to mispairing or mutation. It can also react with the sugar to cause strand breaks then mutations when you repair it.
Failure of repair mechanisms in DNA damage can lead to cancer
How can ROS damage proteins?
It can fragment the protein backbone causing degradation and also changes in side chain formation especially disulphide bonds which cause misfolding and disruption of function e.g. cataracts.
How can ROS damage lipids?
The free radical takes the hydrogen from an unsaturated fatty acids which forms a lipid radical which reacts with oxygen to form a lipid peroxyl radical. This starts a chain reaction as the lipid peroxyl radical then removes hydrogen fro, near by FA. Overall this disrupts the hydrophobic environment and bilayer.
What are some sources of biological oxidants?
Endogenous -
1. Electron transport chain - electrons can escape and react with molecular oxygen to form a super-oxidase.
2. Peroxidases
Exogenous:
1. Radiation
2. Drugs e.g. primaquine
3. Toxins e.g. the herbicide Paraquat
What are the functions of nitric oxide?
Inducible nitric oxide synthase produces high NO conc in phagocytes for toxicity effect.
Endothelial nitric oxide synthase causes vasodilation
Neuronal nitric oxide synthase is a neurotransmission signalling molecules
What is a respiratory burst?
Quick production of superoxide and hydrogen peroxide from phagocytes cells. They destroy invading bacteria. Bodies defence system.
What is a respiratory burst?
Quick production of superoxide and hydrogen peroxide from phagocytes cells. They destroy invading bacteria. Bodies defence system.
What is chronic granulomatous disease?
A NADPH oxidase genetic defect which gives you increased risk of bacterial infections and you do not have the protective effects of NADPH. Infections include pneumonia and cellulitis.
