Alcohol Metabolism

Question 1

How does alcohol metabolism deplete NAD+/NADH?

Answer 1

When it is converted to acetylaldehyde it uses one NAD+ molecule
.when acteylaldehyde is converted into acetate is uses one NAD+ molecule

Question 2

How does a reduced NAD+ concentration lead to hypoglycaemia?

Answer 2

Reduced metabolism of glycerol which means that less gluconeogenesis can occur.

Question 3

How does alcohol metabolism lead to the exacerbation of gout?

Answer 3

.reduced NADP+
.increased conc of lactate which cannot be converted to pyruvate
.the lactate prevents the excretion of Uric acid from the kidneys
.this exacerbates gout

Question 4

What causes gout?

Answer 4

.Defective metabolism of purines produces mono sodium urate crystals
. These get trapped in joints which causes neutrophils to invade
.The crystals destroy these neutrophils causing the release of lysosomal enzymes
. Causing inflammation and pain

Question 5

What is gout?

Answer 5

Red, tender swollen joints. Often sudden onset.

Type of arthritis.

Question 6

How does alcohol metabolism lead to fatty liver?

Answer 6

.the increased concentration of acetyl coA increases triglycerides/ fatty acid synthesis
.however, the liver has low lipoprotein synthesis
.the fatty acids cannot be transported instead they are stored
.this accumulates eventually liver failure, cirrhosis and death

Question 7

What is acetate converted into?

Answer 7

Acetyl coA

Question 8

What product/intermediate of alcohol metabolism causes hang overs/ is toxic to cells?

Answer 8

Acteylaldehyde

Question 9

What enzymes are involved in alcohol metabolism?

Answer 9

Alcohol dehydrogenase

Aldehyde dehydrogenase

Question 10

How does the body ensure acetylaldehyde doesn’t build up in the blood?

Answer 10

Aldehyde dehydrogenase has a very low km for acetylaldehyde.

Question 11

How does alcohol metabolism lead to lactic acidosis?

Answer 11

. Insufficient NAD+ to convert lactate to pyruvate
.There is an increased concentration of lactate
.leading to lactic acidosis

Question 12

What is lactic acidosis?

Answer 12

A build up of lactic acid in the blood reducing its pH resulting in diarrhoea, tiredness, cramps

Question 13

What is hyperbilirubinaemia?

Answer 13

When the liver cells cannot take up conjugated bilirubin it builds up in the blood.
It can lead to jaundice.

Question 14

What are common side effects of a damaged liver?

Answer 14

Hyperbilirubinaemia, hyperammonaemia(can’t produce urea), odema (can’t reduce albumin),

Question 15

What affect can high alcohol consumption have on different organs?

Answer 15

Chronic pancreatitis, issues with GI tract, damage liver cells

Question 16

Excessive alcohol consumption can lead to chronic pancreatitis.what are the effects of this condition on the body?

Answer 16

Damage to pancreatic cells can cause:
.hyperglycaemia if it effects B cells
.glucosuria
.lead to diabetes
.malabsorption from gut as no digestive enzymes produced. (Damaged acini)
. Fever and pain

Question 17

What is the effect of excessive alcohol consumption on the GI TRACT?

Answer 17

.malabsorption of nutrients from gut leading to deficiencies
.loss of apetite

Question 18

What deficiencies can arise for alcoholism?

Answer 18

.thiamine deficiency=Wernicke-Korsakoff
. Vit K
.folic acid= anaemia

Question 19

What drug do you use to treat alcoholism and how does it work?

Answer 19

Diasulfiram
Which inhibits aldehyde dehydrogenase so that acetylaldehyde build up in the blood to a toxic level more easily.
This causes nausea/hangover

Question 20

What is oxidative stress?

Answer 20

When the number of free radicals are greater than the antioxidants in the body

Question 21

Examples of free radicals

Answer 21

.superoxide o2^.
.oh^.
.h2o2
.No^.

Question 22

Examples of antioxidants

Answer 22

GSS
NADPH
VIT E
VIT C

Question 23

What does vit E do as an antioxidant?

Answer 23

Prevents lipid peroxidation

Question 24

How is vit c’s role in stopping lipid peroxidation?

Answer 24

It reduces vit E again, regenerating it

Question 25

How does lipid peroxidation work?

Answer 25

ROS reacts with polyunsaturated fatty acid chain in the plasma membrane. This reacts with oxygen to form a lipid peroxyl radicals A chain reaction occurs as the lipid peroxyl radicals reacts with adjacent fatty acid chains This disrupts the membrane structure

Question 26

How do superoxide radicals form?

Answer 26

The premature reduction of oxygen in the electron transport chai

Question 27

What are respiratory bursts? | .what cells use it

Answer 27

When neutrophils and macrophages release ROS’s to destroy surrounding target cells

Question 28

What are NADPH oxidises and how do they contribute to respiratory bursts?

Answer 28

They are membrane bound enzyme that transfer electrons from NADPH to molecular oxygen producing ROS. These can then be released to bacterial and fungal cells.

Question 29

How does galactosaemia lead to oxidative stress?

Answer 29

Galcactosaemia: Build up of galactose due to deficiency n galactokinase etc results in aldose reductase catalysing the formation of galactitol, using NADPH. NADPH is required by reductase to reduce glutathione GSSG TO GSH which is the first line of defence.

Question 30

How does G6PDH deficiency lead to oxidative stress?

Answer 30

Glucose 6 phosphate cannot be oxidised which would produce NADPH from NAD. NADPH is required by reductase to reduce glutathione GSSG TO GSH which is the first line of defence

Question 31

How does Glutathione work as a antioxidant?

Answer 31

The thiol group on the cysteine residue donates an electron to the ROS. Then it reacts with another GSH molecule, forming sulfide bonds. This is catalysed by glutathione peroxidase It is then converted back to its reduced form by gluathione reductase using NADPH. Recycled

Question 32

What are the enzymes involved in GSH to GSSG

Answer 32

Glutathione peroxidase | Glutathione reductase

Question 33

What effect can ROS have on DNA

Answer 33

Cause mutations leading to cancer

Question 34

Why is mitochondrial DNA especially susceptible to the actions of ROS?

Answer 34

.it is not bound to histones | .it’s situated close to the inner mitochondrial membrane where the ETC’s are

Question 35

How can a high paracetamol dosage cause liver failure?

Answer 35

. Liver damage due to covalent bonding between hepatic proteins .NAPQI conjugates with glutathione, reducing its concentration in the liver, making it more susceptible to oxidative stress.

Question 36

How does haemolytic anaemia cause jaundice?

Answer 36

More RBC’s are being broken down than synthesised in BM This results in high concentration of unconjugated bilirubin into the blood This causes indirect hyperbilirubinaemia This causes jaundice

Question 37

What are reticulocytes?

Answer 37

Immature red blood cells

Question 38

What is the role of G6PD in red blood cells?

Answer 38

They are involved in the pentose phosphate pathway which is the ONLY PATHWAY for synthesises of NADPH for the cell, to maintain glutathione. They protect from damage from oxidative stress and premature destruction