Lecture 34: ALCOHOL METABOLISM Flashcards
What do the effects of alcohol involve?
Activation of the GABA a receptor
What is GABA?
gamma - aminobutyrate, a neurotransmitter derived from glutamate
What is the GABA a receptor?
A membrane bound ligand-gated chloride channel
What happens when GABA a is activated?
It selectively conducts Cl- ions causing an inhibitory effect on neurotransmission by reducing the chance of a successful action potential
What does activation of the GABAa receptor do?
Damps down responses to other stimuli
What do agonists of the GABAa receptor include?
Sedatives such as benzodiazapines and barbiturates as well as alcohol
What is the fuel source from alcohol?
24.9 kJ/g of energy in the bonds
Alcohol is a potential ….
toxin (in large amounts)
What is the rate of absorption and elimination of alcohol?
About 1 drink per hour
What is the first step of alcohol metabolism?
Ethanol >Acetaldehyde which is catalysed by alcohol dehydrogenase
What gets alcohol dehydrogenase to the vmax?
2 drinks
What coenzyme is involved in the first two steps of alcohol metabolism?
NAD+ is reduced to NADH and H+
Acetaldehyde is ….
toxic, so is removed quickly
What happens in the second step of alcohol metabolism?
Acetaldehyde > Acetate catalysed by aldehyde dehydrogenase
What coenzyme is involved in the second step of alcohol metabolism?
NAD+ is reduced to NADH and H+
What are the two forms of aldehyde dehydrogenase?
A cytosolic form and a mitochondrial form (most active)
When do tachycardia and various other issues such as red facial flush occur?
In people carrying a change from Glu to Lys at position 487 in the mitochondrial protein (common variant= 40% of the east asian population)
What is the effect of tachycardia used clinically for?
With a drug called Antabuse that inhibits aldehyde dehydrogenase causing the individual to fell unwell due to build up of aldehyde (nauseous) - reduces desire for alcohol
What happens in the third step of alcohol metabolism?
Acetate + CoA + ATP > acetyl-CoA + AMP + PPi
What may happen with the acetyl CoA produced in the third step of alcohol metabolism?
It may be converted to fatty acids and cause fatty liver or used in the citric acid cycle, electron transport chain and oxidative phosphorylation to produce CO2 and ATP
When is acetyl CoA converted to fatty acids?
When there is already enough ATP present. If there is too much fatty acids, the VLDL’s can take it away to store in adipose tissue resulting in fatty liver or stertosis
What are the consequences of alcohol metabolism?
Increased ratio of NADH:NAD+ and increased ATP as there is nothing regulating breakdown if there is enough energy
What happens as a result of the increased NADH:NAD+ ratio?
It slows the citric acid cycle, electron transport, pyruvate dehydrogenase, glycolysis (phosphofructokinase) and fatty acid oxidation as there isn’t enough NAD+ available
What happens with fatty acids as a result of alcohol metabolism?
They are esterified to TAG (causes fatty liver) and can also result in hypercholesterolaemia and hypertriacylglycerolaemia
What does increased NADH cause?
Pyruvate to convert to lactate which decreases pH- inhibits gluconeogenesis which can cause low blood sugar and coma
What happens in the microsomal ethanol oxidising system?
- ethanol > acetaldehyde using NADPH and O2 >2H20 catalysed by oxidase
- acetaldehyde > acetate using NAD+ catalysed by aldehyde dehydrogenase
What does oxidase also metabolise?
Other drugs and sometimes adverse reactions can occur such as giving rise to reactive oxygen species (by picking up an electron)
What happens in chronic (excessive) alcohol metabolism?
Toxic acetaldehyde + reactive oxygen species > fatty liver + inflammation > alcoholic hepatitis > necrosis > cirrhosis > coma and death
