55 - Glycerophospholipid Synthesis, Degredation, and role in RDS

Glycerophospholipid Functions

• Structural components of

  • membranes

  • lipoproteins

  • surfactant

  • bile

• Precursors for second messengers

  • PIP3 and PIP4

  • DAG

CDP-DAG Pathway makes

• Phosphatidylinositol

• Phosphatidylglycerol

• Cardiolipin

Kennedy Pathway

Pathway where there is the tranfer of activated CDP-choline or CDP-ethanolamine to DAG

Kennedy Pathway Makes

• Phosphatidylcholine

• Phosphatidylethanolamine

• Phosphatidylserine

Phospholipase A2

Enzyme involved in phospholipid degradation:

• when acts on PI, it releases Arachidonic Acid (precursor to eicosanoids)

• inhibited by glucocorticoids such as cortisol

Phospholipase D

Enzyme involved in phospholipid degradation::

• Involed in signal tranduction and

• generates Phosphatidic Acid (PA) and choline from PC and generates DAG from PA

Phospholipase C

Enzyme involved in phospholipid degradation:

• found in liver lysosomes and the alpha toxin of clostiridia and other bacilli

• Membrane bound, it is activated by PIP2 system and is thus involved in producing second messengers

Surface Tension

The property of a liquid's surface that allows it to resist an external force, due to the cohesive nature of its molecules. It is a measure of the elastic-like force existing at the surface of a material.

Role of Phospholipids in Alveolar Function

These molecules penetrate though the air-water interface to reduce intermolecular hydrogen bonding between water molecules, forming a monolayer, which lowers surface tension and prevents alveolar collapse

Composition of Lung Surfactant

• Phospholipids

  • 70% PC

  • other glycerophospholipids

  • Sphingomyelin

• Cholesterol

• Proteins (10%)

SP-A and SP-D

Proteins in surfactant that play a role in innate host defence, have antimicrobial properties, and help regulate inflammation

SP-B and SP-C

Proteins in surfactant that interact strongly with PLs, preventing collapse of the alveolus

• mutations in genes coding for these molecules are causes of severe pulmonary disease

Alveolar Type II cell

Makes Surfactant in ER and recycles it in its lysosomes

Macrophage

Degrades Lung Surfactant

Respiratory Distress Syndrome

• Most common cause of respiratory distress in preterm infants

• Etiology: structural and functional lung immaturity due to undeveloped parenchyma and surfactant deficiency, resulting in unstable alveoli

Determining Lung Maturity

determining the PC ratio to SM ratio in amniotic fluid

Lung Maturity Value

PC/SM (L/S) > 2

Corticosteroids

Administration before delivery speeds up lung development and surfactant production

Acute Respiratory Distress Syndrome

Seen in critical care units; increased capillary permeability leads to leakage of surface-active blood and serum proteins into air spaces. This results in impairment of surfactant function.