Antitrypsin deficiency

1. Alpha 1 Antitrypsin
Deficiency
By Kyla Turnquist

2. Overview of Disease
• Alpha-1-antitrypsin
deficiency leads to a
condition known as Chronic
Obstructive Pulmonary
Disease (COPD) or
emphysema of the lungs.
• Clinically
– Shortness of breath
– ‘barrel chest’

3. Overview of Disease
• Liver Disease
– Alpha 1 Antritrypsin secreted from the liver
– The improperly folded protein cannot be secreted,
and buildup causes liver damage.
• Clinically
– Cirrhosis may develop in patients with alpha-1-
antitrypsin deficiency
– Reduced liver function
– Inflammation of liver severe fibrosis of the liver
– Liver failure

4. Genotype
• There are many variants for alpha1 AT
Deficiency
• Most common in the United States is the S
variant (SS) others include MS, MZ, or ZZ
• The Z variant is due to a substitution on
the distal end of chromosome 14,
(Location: 14q32.1 ) worst variant
• Most commonly the substitution is
Glutamic acid is replaced by lysine at
position 342 (Glu342Lys).

5. Protein Function
• The normal function of the alpha 1
antitrypsin is to counteract the effects of
neutrophil elastase
– Enzyme in the lung used to destroy bacteria,
cellular debri
– Without the inhibition of neutrophil elastase,
the enzyme destroys tissue surrounding
alveoli, causing trapped air emphysema.
– A1AT functions in other organs, but main
damage occurs in lungs

6. Image of A1AT protein

7. Secondary and Tertiary Structure

8. Point Mutation of Glutamic Acid to
Lysine at position 342

9. Changes in Function of Protein
• The variant of glutamic acid to lysine
causes a slight difference in the folding of
the protein which inhibits normal function.
• The amino acid interacts with surrounding
amino acids causing the abnormal fold.

10. Changes in Phenotype
• The abnormal folding inhibits proper
function of the protein. It therefore cannot
escape the liver, causing liver disease and
cirrhosis due to scarring. The non-
functioning protein cannot protect the
lungs against the enzyme nuetrophil
elastase, and emphysema develops.

11. Works Cited
Lai, E. C.; Kao, F.-T.; Law, M. L.; Woo, S. L. C. :
Assignment of the alpha-1-antitrypsin gene
and a sequence-related gene to human
chromosome 14 by molecular hybridization.
Am. J. Hum. Genet. 35: 385-392, 1983.
PubMed ID : 6602546
• Bethesda (MD). Genes and disease. National
Library of Medicine (US), NCBI.
• Axelsson, U.; Laurell, C. B. : Hereditary
variants of serum alpha-1-antitrypsin. Am. J.
Hum. Genet. 17: 466-472, 1965.
PubMed ID : 4158556