Alcohol & Oxidative Stress Flashcards
Describe the metabolism of alcohol:
Ethanol is first broken down to Acetaldehyde by alcohol dehydrogenase.
Acetaldehyde is then broken down to Acetate by aldehyde dehydrogenase.
Two molecules of NAD+ are reduced to NADH in the process.
How does the metabolism of alcohol cause damage to the liver?
The intermediate acetaldehyde is toxic.
High levels of this molecule will damage the liver.
It also reduces NAD+ levels so that the liver is unable to carry out B-oxidation, the conversion of lactate to pyruvate and glycerol metabolism.
The buildup of lactate may lead to lactic acidosis.
What is disulfiram used for and what is its method of action?
Used to treat those with chronic alcohol dependence.
Works by inhibiting aldehyde dehydrogenase so that those taking the drug experience severe hangovers.
This acts as a deterrent.
How are superoxide radicals made by mitochondria?
In the mitochondrial inter-membrane space oxidative phosphorylation occurs.
Some electrons may escape from the electron transport chain and reduce oxygen to the superoxide radical.
Name reactive oxygen and nitrogen species:
Oxygen:
Superoxide (O2-)
Hydroxyl Radical (OH*)
Hydrogen Peroxide (H2O2)
Nitrogen:
Nitric Oxide (NO*)
Peroxynitrite (ONOO-)
Outline the defense mechanisms against ROS:
Free radical scavengers
Superoxide Dismutase
Catalase
Glutathione
What are free radical scavengers and how do they work?
Vitamins C and E
They work by donating a hydrogen atom (and its electron) to free radicals in order to pair up the free electron.
Describe how superoxide Dismutase and catalase work together to neutralise ROS:
Superoxide dismutase converts superoxide into hydrogen peroxide and oxygen.
Catalase then converts hydrogen peroxide into oxygen and water.
Describe how glutathione (GSH) works to protect against ROS:
Glutathione donates an electron to a ROS and reacts with another glutathione to form GSSG.
This reaction is catalysed by glutathione peroxidase.
GSSG must then be converted back to GSH so it can be reused.
NADH is needed to reduce GSSG to GSH in a reaction catalysed by glutathione reductase.
Why is the pentose phosphate pathway important in the defense against ROS?
It provides lots of NADH which is needed to reduce GSSG back to GSH
Define oxidative stress:
Oxidative stress arises when the body’s antioxidant defences are unable to cope with the level of oxidants.
What is a respiratory burst?
A defence mechanism utilised by leucocytes.
Pathogens are engulfed by the leucocyte and a lysosome formed.
ROS are then formed in the lysosome and damage the pathogen.
How can galactosaemia contribute to oxidative stress?
In galactosaemia galactose can’t be metabolised due to dysfunction in the enzymes galactokinase or uridyl transferase.
Instead galactose is converted to galactitol by aldose reductase. This process needs NADH.
Because NADH is being used by aldose reductase, less is able to reduce GSSG back to GSH. The lack of GSH causes oxidative stress.
How can a G6PDH deficiency contribute to oxidative stress?
G6PDH is the first enzyme in the pentose phosphate pathway which produces NADH.
A deficiency in this enzyme means a deficiency in NADH.
NADH is needed to convert GSSG back to GSH.
Because there are lower levels of glutathione then oxidative stress increases.
