lecture 34 - alcohol metabolism Flashcards
What receptor does alcohol act as an agonist of?
GABA A receptor
How does alcohol affect the nervous system?
Acts as an agonist of the GABA A receptor causing an increase in the inhibitory effect on neurotransmission.
What type of receptor is the GABA A receptor?
Membrane bound ligand-gated chloride channel
What happens when the GABA A receptor is activated?
Selectively conducts Cl- ions causing an inhibitory effect on neurotransmission by reducing the chance of a successful action potential.
Does alcohol amplify or dampen the effects of a GABA A receptor?
Amplifies, as it is an agonist, increasing the number of chloride molecules that cab pass through
What is the chemical we know as alcohol?
Ethanol
Why is alcohol rapidly absorbed into the blood?
Small molecule that does not require enzymatic digestion, so will be readily absorbed and then metabolised.
What is alcohol/ethanol converted to when it first enters the body?
Acetaldehyde
What enzyme is needed to convert ethanol to acetaldehyde?
Alcohol dehydrogenase
What is alcohol dehydrogenase coupled to when forming acetaldehyde from ethanol?
NAD+ is converted to NADH and H+
What is acetaldehyde converted to by aldehyde dehydrogenase?
Acetate
What enzyme is used to convert acetaldehyde to acetate?
Aldehyde dehydrogenase
What is the acetaldehyde to acetate reaction coupled to?
The conversion of NAD+ to NADH and H+
How does acetate form Acetyl CoA?
Using Acetyl CoA synthetase enzyme. CoA and ATP are fed into the reaction, AMP and PPi produced
What are the consequences of alcohol metabolism on the citric acid cycle and electron transport chain?
Slows CAC and ETC by increasing the NADH to NAD+ ratio
What is the effect of alcohol metabolism on fatty acids?
They are esterified to TAG, which can cause a build up in the liver - ‘fatty liver’ as well as high blood cholesterol and TAG concentrations
What is the consequence of alcohol metabolism on pyruvate?
Increases the NADH to NAD+ ratio, which causes the pyruvate to lactate reaction, which decreases the pH of the liver.
What is the consequence of alcohol metabolism on gluconeogenesis?
Increases [NADH], which inhibits gluconeogenis which can lead to low blood glucose between meals.
What happens to the ratio of NADH to NAD+ when alcohol is metabolised?
Increased NADH, decreased NAD+. Increased NADH/NAD+
Where is the majority of ethanol metabolised?
The liver
What system metabolises alcohol when it is treated as a toxin?
The microsomes ethanol oxidising system
What product of ethanol metabolism is toxic?
Acetaldehyde
What can the oxidase in ethanol metabolism give rise to?
Reactive oxygen species
What is the outcome of chronic fatty liver and inflammation?
Alcoholic hepatitis
What are the outcomes of alcoholic hepatitis?
necrosis, cirrhosis, then coma and death
What builds up in liver dysfunction?
NH3
What limits the rate of alcohol metabolism?
Alcohol dehydrogenase becomes saturated after a couple of drinks, meaning it can only catalyse the reaction to acetaldehyde at a limited rate.
What is the impact of alcohol metabolism on citrate levels?
By limiting the CAC and ETC, citrate builds up
What is the mechanism by which fatty liver occurs?
Excess alcohol intake causes reduced fatty acid metabolism due to a depletion in NAD+. Fatty acids are instead converted to TAGs, which build up in the liver.
