Introduction Structure of the protein Hubs network with other's protein Function Incase of Deficiency Case study Conclusion References

1. AHMAD ALI
MOLECULAR DIAGNOSTIC AND BIOTECHNOLOGY

2. Table of Content
Introduction
Structure of the protein
Hubs network with other's protein
Function
Incase of Deficiency
Case study
Conclusion
References

3. Introduction:
Also known as α1-antiproteinase.
Alpha-1-antitrypsin is a glycoprotein with a molecular weight of 54 kDa and
pI of 4.8.
Single polypeptide chain having 394 amino acids.
Normal level = 75- 200 mg/dL
Protein family: (Glycoprotein) It is encoded in humans by the SERPINA1
gene.

4. Cont’d
SERPINA1
Alpha 1-antitrypsin (white) with highlighted 'reactive Centre loop' (blue)
and A-sheet (light blue).
SERPINA1 gene provides instructions for making a protein
called alpha-1 antitrypsin, which is a type of serine protease
inhibitor (serpin)

5. The pharmaceutical form is purified from human donor
blood and is sold under the nonproprietary name.
Alpha1–proteinase inhibitor (human) and under various
trade names (including Aralast NP, Glassia, Prolastin,
Prolastin-C, and Zemaira).
Recombinant versions are also available but are currently
used in medical research more than as medication.

6. Cont’d
ARALAST NP is a sterile, lyophilized preparation of purified human alpha1-proteinase inhibitor (Alpha1-
PI), also known as alpha1-antitrypsin (AAT).

7. Hub Network Alpha Antitrypsin

8. Cont’d

9. Cont’d
Protein Hubs
Highly connected nodes (proteins) are called hubs.
Han et al. have coined the term "party hub" for hubs whose
expression is correlated with its interaction partners. Party hubs also
connect proteins within functional modules such as protein
complexes.

10. Protein Hub’s……Cont’d
Protein Hubs
Han et al.

11. Function of Alpha Antitrypsin 1
Function:
Inhibit the action of elastase,trypsin and other
proteases
Tumour marker of testis and ovaries.
Inhibits fibrinolysis.

12. Cont’d
Inhibit the action of elastase,trypsin and other
proteases:
Alpha-1 antitrypsin protects the lungs from neutrophil elastase, which can
damage lung tissue if not properly controlled. Alpha-1 antitrypsin is produced in
the liver and then transported to the lungs via the blood.
neutrophil elastase is excessively free to break down elastin, degrading the
elasticity of the lungs, which results in respiratory complications, such as chronic
obstructive pulmonary disease, in adults.

13. Cont’d
Tumour marker of testis and ovaries.
Alpha-1 antitrypsin (AAT) and alphafoetoprotein (AFP) in
sera of patients with germ-cell neoplasms: value as tumour
markers in patients with endodermal sinus tumour (yolk sac
Tumour).

14. Cont’d
Inhibits fibrinolysis
Hemostasis and fibrinolysis, the biological processes that maintain
proper blood flow, are the consequence of a complex series of
cascading enzymatic reactions.
In the pathological conditions of thrombosis or abnormal bleeding,
The delicate balance between proteolytic and inhibitory reactions in
hemostasis and fibrinolysis, described by the coagulation, protein C
and fibrinolytic pathways, can be disrupted by the Alpha trypsin 1.

15. Incase of Deficiency
Case Study:
A 42 year old woman presented with chronic cough, excessive
production of mucus and shortness of breath.
Upon exercising, she started to hyperventilate and her tolerance
seemed to be decreasing. She often suffered from dizziness and
anxiety.
There was also an abnormal weight loss and her fingers used to turn
blue or grey.

16. Cont’d
?
What is the diagnosis?
On examining the blood sample, there was a
low level of AAT.

17. Emphysema
About 5% of emphysema cases are due to α- 1 antitrypsin deficiency. Patients
with zz genotype having less protein are more susceptible to this deficiency.
Any bacterial infection in lungs attracts macrophages that release elastase. In
normal health, α- 1 antitrypsin protects the lung tissues from injury by binding
with the active elastase, making it inactive.
However in α- 1 antitrypsin deficiency, there is unopposed action of the active
elastase leading to serious lung tissue damage through proteolysis.
This condition whereby most of the elastin surrounding the alveoli are damaged
is called Emphysema.

18. Feed back……Cont’d

19. Cont’d
Case discussion
Smoking oxidizes methionine to methionine sulfoxide at 358 th
position.
Hence it deactivates AAT and causes tissue damage, resulting in
EMPHYSEMA.
Damage from emphysema is irreversible.
Nevertheless giving up smoking is quite beneficial.

20. Emphysema is a progressive, incurable chronic lung condition.
The air sacs (alveoli) are destroyed and oxygen uptake is
restricted due to the loss of elasticity of lung tissue.

21. Incase of Increase
2nd Case Study
A 15 year-old female presented with itching, weakness, fatigue, and
loss of appetite. She was found to be having a low serum albumin
concentration, together with a marked increase in the concentration of
Alanine amino Transferase ( ALT) and Aspartate Transferase (AST).
Serum total Bilirubin concentration was also found to be higher, the
patient apparently had Jaundice?

22. Case discussion
Cirrhosis detection
The patient is suffering from Juvenile hepatic cirrhosis
Thus they are unable to release AAT leading to the cirrhosis of
liver.

23. Cirrhosis
PiZ Molecules
alpha-1 antitrypsin
(AAT) mutant variant is
a missense mutation
(E342K), commonly
referred to as PiZ

24. Conclusion
Alpha-1 antitrypsin (AAT) is a protein in the blood that protects the
lungs from damage caused by activated enzymes.
importance of proteasomal and autophagic degradative pathways in
disposal of liver disease-associated protein aggregates.
α1-Antitrypsin deficiency is a common genetic condition that can be
involved in premature lung and liver disease. Consider the diagnosis
to allow earlier institution of AAT augmentation therapy to slow the
progression of premature lung disease in affected patients.

25. Summary

26. References
Han etal…
Biochemistry for medics
Internet
Google Schlor
PubMed