Lecture 34: ALCOHOL METABOLISM

Question 1

What do the effects of alcohol involve?

Answer 1

Activation of the GABA a receptor

Question 2

What is GABA?

Answer 2

gamma - aminobutyrate, a neurotransmitter derived from glutamate

Question 3

What is the GABA a receptor?

Answer 3

A membrane bound ligand-gated chloride channel

Question 4

What happens when GABA a is activated?

Answer 4

It selectively conducts Cl- ions causing an inhibitory effect on neurotransmission by reducing the chance of a successful action potential

Question 5

What does activation of the GABAa receptor do?

Answer 5

Damps down responses to other stimuli

Question 6

What do agonists of the GABAa receptor include?

Answer 6

Sedatives such as benzodiazapines and barbiturates as well as alcohol

Question 7

What is the fuel source from alcohol?

Answer 7

24.9 kJ/g of energy in the bonds

Question 8

Alcohol is a potential ….

Answer 8

toxin (in large amounts)

Question 9

What is the rate of absorption and elimination of alcohol?

Answer 9

About 1 drink per hour

Question 10

What is the first step of alcohol metabolism?

Answer 10

Ethanol >Acetaldehyde which is catalysed by alcohol dehydrogenase

Question 11

What gets alcohol dehydrogenase to the vmax?

Answer 11

2 drinks

Question 12

What coenzyme is involved in the first two steps of alcohol metabolism?

Answer 12

NAD+ is reduced to NADH and H+

Question 13

Acetaldehyde is ….

Answer 13

toxic, so is removed quickly

Question 14

What happens in the second step of alcohol metabolism?

Answer 14

Acetaldehyde > Acetate catalysed by aldehyde dehydrogenase

Question 15

What coenzyme is involved in the second step of alcohol metabolism?

Answer 15

NAD+ is reduced to NADH and H+

Question 16

What are the two forms of aldehyde dehydrogenase?

Answer 16

A cytosolic form and a mitochondrial form (most active)

Question 17

When do tachycardia and various other issues such as red facial flush occur?

Answer 17

In people carrying a change from Glu to Lys at position 487 in the mitochondrial protein (common variant= 40% of the east asian population)

Question 18

What is the effect of tachycardia used clinically for?

Answer 18

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

Question 19

What happens in the third step of alcohol metabolism?

Answer 19

Acetate + CoA + ATP > acetyl-CoA + AMP + PPi

Question 20

What may happen with the acetyl CoA produced in the third step of alcohol metabolism?

Answer 20

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

Question 21

When is acetyl CoA converted to fatty acids?

Answer 21

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

Question 22

What are the consequences of alcohol metabolism?

Answer 22

Increased ratio of NADH:NAD+ and increased ATP as there is nothing regulating breakdown if there is enough energy

Question 23

What happens as a result of the increased NADH:NAD+ ratio?

Answer 23

It slows the citric acid cycle, electron transport, pyruvate dehydrogenase, glycolysis (phosphofructokinase) and fatty acid oxidation as there isn’t enough NAD+ available

Question 24

What happens with fatty acids as a result of alcohol metabolism?

Answer 24

They are esterified to TAG (causes fatty liver) and can also result in hypercholesterolaemia and hypertriacylglycerolaemia

Question 25

What does increased NADH cause?

Answer 25

Pyruvate to convert to lactate which decreases pH- inhibits gluconeogenesis which can cause low blood sugar and coma

Question 26

What happens in the microsomal ethanol oxidising system?

Answer 26

1. ethanol > acetaldehyde using NADPH and O2 >2H20 catalysed by oxidase
2. acetaldehyde > acetate using NAD+ catalysed by aldehyde dehydrogenase

Question 27

What does oxidase also metabolise?

Answer 27

Other drugs and sometimes adverse reactions can occur such as giving rise to reactive oxygen species (by picking up an electron)

Question 28

What happens in chronic (excessive) alcohol metabolism?

Answer 28

Toxic acetaldehyde + reactive oxygen species > fatty liver + inflammation > alcoholic hepatitis > necrosis > cirrhosis > coma and death