Emerging techniques

Question 1

What is the single largest group of genetic diseases

Answer 1

in born errors of metabolism

Question 2

give examples of inborn errors of metabolism

Answer 2

PKU
MCAD
homocystinurea
Maple syrup urine disease

Question 3

Describe when happens in inborn errors of metabolism and why a lack of an enzyme causes diseases to occur (3)

Answer 3

1) if you lack an enzyme you will lack a product
2) increase substrate
3) increase alternative products from that substrate

Question 4

What type of disease is phenylketonurea

Answer 4

inborn error of metabolism

Question 5

What enzyme is not present in phenyketonurea

Answer 5

phenylalanine hydroxlasae

Question 6

Describe the pathophysiology of PKU

Answer 6

1) phenylalanine is the substrate and it should be converted into tyrosine by phenylalanine hydroxylase
2) in PKU phenylalanine hydroxylase is not present
3) so it is converted by an alternative pathway into phenylketones

Question 7

Describe the symptoms of PKU

Answer 7

1) cognitive and behavioural difficulties
2) fairer eyes, hair and skin due to lack of melanin
3) recurrent vomiting

Question 8

How is PKU currently treated

Answer 8

1) low protein diet

2) supplemented with tyrosine

Question 9

Give an example of a disease involving loss of factors

Answer 9

1) haemophilia

Question 10

What are some symptoms of haemophilia

Answer 10

increased bruising
bleeding into joints and brain
uncontrolled bleeding
fatal if untreated

Question 11

What is the current treatment for hemophilia A

Answer 11

recombinant factor VIII treatment

Question 12

Give examples of other diseases that are treated by replacement

Answer 12

1) Growth hormone deficiency is treated by recombinant growth hormone (used to be from cadavers but they developed CVJ disease)
2) Lysosomal storage diseases (Fabry disease by alpha galactosidase A and pompe disease by alpha glucosidase)

Question 13

What are the general principles involved in the treatment of PKU and hemophilia A

Answer 13

1) PKU is treated by diet and supplement
2) Hemophilia A is treated by supplement
3) you need to know the underlying biochemistry involved
4) but you don’t need to know the specific gene involved
5) NOT mutation specific

Question 14

What are 3 key characteristics of pharmacological treatments targeting proteins

Answer 14

1) treat condition and not symptoms
2) treatments not cures (will have to take treatment for the rest of their lives)
3) tries to normalise function of a mutant protein

Question 15

Describe protein folding in the ER with molecular chaperones

Answer 15

1) has a co translational interaction with molecular chaperones to form a folding intermediate
2) some can end up in a misfolded state due to a mutation and undergo a degradation pathway

Question 16

How does Migalastat work

Answer 16

1) pharmacological chaperone for
2) fabry disease
3) rescues the folding process so it doesn’t go down the degradation pathway
4) Some mutations that cause Fabry disease causes protein misfolding

Question 17

What molecule does Migalastat resemble

Answer 17

the substrate of alpha galactosidase A which is beta D galactose

Question 18

What is Fabry disease

Answer 18

deficiency of alpha galactosidase A

Question 19

How do pharmacological modulators work

Answer 19

1) receptor agonist/antagonist

2) ion channel agonist/antagonist

Question 20

Give an example of using pharmacological modulators to work on a cancer

Answer 20

works to agonise BCL - ABL kinase inhibitors

Question 21

How are pharmacological modulators used to treat cystic fibrosis

Answer 21

• some mutations cause chloride channel not to open