lecture 4 - acute phase response & alpha-1-antitrypsin

Question 1

What is the function of Alpha-1-Antitrypsin?

Answer 1

Protease inhibitor that binds with elastase to prevent it from breaking down elastin in connective tissues, which can otherwise lead to lung and liver damage.

Question 2

What is the mechanism of inhibition of Alpha-1-Antitrypsin?

Answer 2

Binds 1:1 with elastase, and acts as a suicide inhibitor, to irreversibly cleave elastase.

Question 3

What is a SERPIN?

Answer 3

Serine Protease Inhibitor

Question 4

What type of inhibitor is Alpha-1-Antitrypsin?

Answer 4

SERPIN - Serine Protease Inhibitor

Question 5

What gene is involved in Alpha-1-Antitrypsin deficiency?

Answer 5

SERPINA1

Question 6

What diseases are people with Alpha-1-Antitrypsin deficiency prone to?

Answer 6

Emphysema, Chronic Obstructive Pulmonary Disease, liver disease

Question 7

What are the treatments of Alpha-1-Antitrypsin deficiency (AATD)?

Answer 7

reduce environmental damage (e.g. smoking), genetic counselling, exercise, IV AAT augmentation in emphysema, transplant (liver/lungs)

Question 8

Where is Alpha-1-Antitrypsin produced?

Answer 8

The liver

Question 9

What gene-environment interaction is common and increases mortality in AATD?

Answer 9

Smoking and PI*ZZ alleles - increase lung function decline

Question 10

Why does cigarette smoking worsen the symptoms of a patient with alpha-1-antitrypsin deficiency?

Answer 10

Smoking inactivates alpha-1-antitrypsin by oxidising an amino acid in its active site, which in particular leads to emphysema.

Question 11

Why might individuals with alpha-1-antitrypsin deficiency present with jaundice?

Answer 11

High bilirubin levels in the blood due to liver disease

Question 12

What is the preferred substrate of alpha-1-antitrypsin in vivo?

Answer 12

elastase

Question 13

What is a serine protease?

Answer 13

An enzyme which cleaves peptide bonds, with serine acting as the nucleophile in its active site