Alcohol Metabolism + Oxidative Stress Flashcards
Where is alcohol metabolised?
> 90% is metabolised in the liver, the rest is excreted in urine and in breath.
Describe alcohol metabolism
Alcohol is oxidised by alcohol dehyrdrogenase to acetaldehyde, then to acetate by aldehyde dehydrogenase.
What causes a ‘hangover’
Acetaldehyde is a toxic metabolite, an accumulation of this causes the hangover
How is acetate used?
It is conjugated to coenzyme A to form acetyl-CoA, then it’s metabolised in TCA cycle or is utilised for fatty acid synthesis.
What are the consequences of increased acetyl-CoA?
This leads to increased synthesis of fatty acids and ketone bodies -> increased synthesis of triacylglycerol -> Fatty liver.
What is used to treat alcohol dependence?
Disulfiram is used as it is an inhibitor of aldehyde dehydrogenase, so patients will have symptoms of a ‘hangover’.
What is a free radical?
An atom or molecule that contains one or more unpaired electron
What is ROS equation?
Oxygen-> Superoxide-> Hydrogen peroxide-> water + Hydroxyl radical
What is RNS equation?
Superoxide + Nitric oxide -> Peroxynitrite
What are the two main types of ROS damage to DNA?
ROS reacts with base- modified base can lead to mispairing and mutation. ROS reacts with sugar- can cause strand break and mutation on repair.
How can ROS damage proteins?
Can react with backbone-> fragmentation-> Protein degradation. Can react with sidechain-> modifies amino acid-> change in protein structure-> Protein degradation/Loss of function/Gain of function.
How can ROS damage damage lipids?
Causes lipid peroxidation-> hydrophobic environment of bilayer disrupted and membrane integrity fails.
How does respiratory burst destroy bacteria?
There’s a rapid production of superoxide and H2O2 from phagocytic cells. ROS and peroxynitrite destroy invading bacteria.
Roles of superoxide dismutase and catalase?
SOD coverts superoxide to H2O2 and oxygen. Catalase coverts hydrogen peroxide to water and oxygen.
Role of glutathione?
GSSG reduced back to GSH by glutathione reductase which catalysed the transfer of electrons from NADPH to disulfide bond. NADPH is essential for protection against free radical damage.
What are free radical scavengers?
They reduce free radical damage by donating hydrogen atom to free radicals. Vitamin E is a lipid soluble antitoxidant, Vitamin C is a water soluble antitoxidant.
What are Heinz bodies?
They are aggregates of haemoglobin, a clinical sign of G6PDH deficiency.
Describe NAPQI.
A toxic metabolite which has direct toxic effects-> oxidative damage to liver cell: Lipid peroxidation/damage to proteins/damage to DNA.
