Recognize the biochemical structure and function of pulmonary surfactant Discuss biochemical basis of respiratory distress syndrome List the differences between collagen and elastin. Identify the biochemical basis of lung emphysema due to alpha one antitrypsin deficiency. Outline the biochemical and molecular basis of cystic fibrosis Mention the diagnosis and treatment of cystic fibrosis

1. Biochemical and molecular
basis of lung diseases
Associate Prof. Dr. Hatim El-Baz
Associate Prof. Dr. Eman Khairy

2. Intended Learning Outcomes
By the end of this lecture, You should be able to:
1. Recognize the biochemical structure and
function of pulmonary surfactant
2. Discuss biochemical basis of respiratory
distress syndrome
3. List the differences between collagen and
elastin.
4. Identify the biochemical basis of lung
emphysema due to alpha one antitrypsin
deficiency.
5. Outline the biochemical and molecular basis of
cystic fibrosis
6. Mention the diagnosis and treatment of cystic
fibrosis.

3. Case Scenario
A newborn boy was delivered at 35
weeks by cesarean section for breech
presentation and premature labor. He
weighed 1750 g and appeared vigorous,
with spontaneous respirations.

4. Case Scenario
Shortly thereafter, subcostal
retractions, nasal flaring and gasping
developed. His color was cyanosed.
Continuous positive airway pressure
(CPAP) was administered, and he
showed improvement.

5. A diagnosis of
Respiratory Distress
Syndrome (RDS)
was made.

6. • In premature babies, the lungs are
developmentally deficient in lung surfactant

7. • The surface tension of
the moist inner
surface originates
from the attraction
between the molecules
of the alveolar fluid.
• Without prevention
this would result in
lung collapse.
• Surfactant lowers
the surface tension
at the alveolar air-
fluid interface

8. Dipalmityl Phosphatidyl choline =
Dipalmityl lecithin= Lung surfactant
- It contains palmitic acid at C1,2
- It decrease the surface tension in the
lung alveoli.
- So, it prevent adherence of the inner
surfaces of the lung.
- At, birth if decrease----- it leads to
“RDS” respiratory distress syndrome

9. Dipalmitoyl Phosphatidyl choline
1-
• Glycerol
2-
• Palmitic acid at C1&2
3-
• Phosphoric acid and choline.

10. Elastin
Major protein component
of elastic tissues such as
arteries, lungs, skin
Highly cross linked ,insoluble
amorphous synthesized from a
precursor tropoelastin (700 A.A).
Rubber like consistency

11. It is composed of soluble tropoelastin
protein (700 amino acids)
It Contain
glycine
valine
alanine
proline.
Rich in lysine
Little hydroxyproline
No hydroxylysine
Tropoelastin (elastin precursor)

12. Tropoelastin molecules
tropoelastin is aggregates
with microfibrils (fibrillin)
Crosslinking of
tropoelastins with each
other by lysyl oxidase →
the spontaneous formation
of desmosine cross-links to
form polymers(network)
Elastic fibers synthesis
Elastin
Microfibrils
Elastic
fibers

13. Cross-link in elastin by desmosine
The inter chain cross-link in elastin is
the result of the conversion of the
amino group of lysine to aldhyde (CHO)
group in allylysine by lysyl oxidase
enzyme.
Elastin
chain
Elastin
chain

14. Then the spontaneous formation of desmosine cross-links.
Desmosine is formed from 1 lysine and 3 allysine residues
Cross-link in elastin by desmosine
CH
NH
CO
CH2 CH2 CHO
CH2 CH
NH
CO
CH2
CH2
CHO CH2
Lysine
Allysine
CH
NH CO
CH2
CH2
CH2
CH2
NH3
+
CH
NH
CO
CH2
CH2
CH2
CHO
Allysine
Allysine
 CH
NH
CO
CH2 CH2  CH
NH
CO
CH2
CH2
 CH
NH CO
CH2
CH2
CH2
CH2
N+
 CH
NH
CO
CH2
CH2
CH2
C
C
C
C
C
Desmosine

15. Collagen Elastin
Many different types Single type
Triple helix No (random coils)
(Gly-x-y)n No
Hydroxylysine is present No
Contain carbohydrate No
Intramolecular cross-links Intramolecular desmosine
cross-links
Widely distributed Large blood vessels, skin
,elastic ligaments
High tensile strength + no
stretch
Stretch+ recoil
Differences of elastin from collagen

16. •Elastin is highly
stable up to 70 years
•Elasin is degraded
by elastase enzyme
which releases by
neutrophils.
Elastin degradation

17. Alpha 1-antitrypsin
• It is a single-chain glycoprotein
• It is formed by liver
• It is a protease inhibitor
• It protects tissues from enzymes of
inflammatory cells, especially neutrophil
which secrete neutrophil elastase
• In deficiency of alpha 1-antitrypsin :
Due to genetic cause or liver disease
Neutrophil elastase is free to break
destruction elastin in lung, which contributes
to the elasticity of the lungs, resulting
in emphysema.
• Diagnosis
Decreased alpha 1-antitrypsin levels in blood

18. Role of 1-antitrypsin (1-AT) in elastin degradation
(Alpha one antitrypsin deficiency)
Deficiency of 1-
antitrypsin results
in emphysema.
Damage to the lung air
sacs (alveoli) that affects
breathing

19. Cystic fibrosis (CF)
 It is an inherited (genetic) multisystem disorder
of children and adults disorder
 It affects mostly the lungs & GIT & Pancreas
 But also can affect liver, kidneys, intestine.
 Genital system.

20. Etiology
• Genetically transmitted disease from both
parents
• Due to mutation in cystic fibrosis
transmembrane conductance regulator protein
(CFTR) gene
• CFTR Gene located on 7th chromosome
• CF is a inherited autosomal recessive disorder
in children
• 2 copies of genes needed to manifst disease
• Carrier states when one copy only is affected
• It is the most common cause of chronic lung disease
in children

21. CFTR Protein Function and Biochemistry
CFTR protein controls chloride ion movement
in and out of the cell in the:
 Lungs
 Liver
 Pancreas
 Digestive tract
 Reproductive tract
Sweat glands in skin.

22. Pathophysiology of cystic fibrosis
Normal
• CFTR gene encodes for
CFTR protein
• This protein controls the
transport of chloride
through chloride channels
from inside cells to the
lumen of the glands
• Therefore, under normal
circumstances, sodium and
chloride remain in the lumen
and keep water there
osmotically across the
epithelial membranes of the
lungs, pancreas, and other
organs.
Cystic fibrosis all
affected tissues
• Defect in CFTR gene
Defect in CFTR protein
• Defect in chloride channels
too little chloride
transported into lumen
• Secondarily, too little sodium
is transported into lumen
resulting in decreasing
osmotic transport of water
into lumen.
• The result is low volume, dry
and thick secretions
obstruction & infections

23. Medical aspects of Cystic Fibrosis
o Impaired lung clearance of mucous
o Recurrent lung infection and inflammation
o Pancreatic damage
oImpaired digestion

24. Symptoms and signs of CF in respiratory system
The thick and sticky mucus associated with cystic
fibrosis block the tubes that carry air in and out of
lungs.
This can cause signs and symptoms such as:
• A persistent cough to excrete stagnant thick
mucus (sputum)
• Breathlessness
• Exercise intolerance
• Repeated lung infections

25. Diagnosis of cystic fibrosis
Positive
family history
• As affected
sibling
Clinically
• Chronic
obstructive
pulmonary
disease
• Exocrine
pancreatic
insufficiency
Positive Sweat
chloride test
Positive
Genetic test

26. Treatment:
• Aimed at relieving symptoms and complications
– Antibiotics
– Mucus-thinning drugs
• Thins secretions
• Easier to cough up
– Bronchodilators :Relaxes smooth muscles in
the airway
– Oral enzymes and better nutrition

27. References
•"Lippincott's Illustrated Reviews in Biochemistry"
by P.C.Champe, R.A.Harvey and D.R. Ferrier.
•"Harper's Biochemistry" by R.K.Murray,
D.K.Granner, P.A. Mayes and V.W. Rodwell.