Complex Lipid Metabolism and Surfactants

Complex Lipid Metabolism

• Phospholipids are amphipathic molecules, meaning they have both hydrophilic (water-loving) and hydrophobic (water-fearing) regions.
• The hydrophilic head of a phospholipid interacts with the intracellular or extracellular aqueous environment.
• The hydrophobic tail interacts with the nonpolar portions of other membrane constituents like glycolipids, proteins, and cholesterol.
• Phospholipids are the predominant lipids in cell membranes.
• Phospholipids also function as a reservoir for intracellular messengers and anchor for some proteins.
• Nonmembrane-bound phospholipids serve additional functions, including components of lung surfactant and bile.

Role of Phosphatidylcholine (PC) in Lung Surfactant

• Di-palmitoyl phosphatidylcholine (DPPC) is a major component of lung surfactant.
• DPPC is made and secreted by Type II pneumocytes.
• Lung surfactant is an extracellular fluid layer lining the alveoli.
• Surfactant decreases surface tension of this fluid layer, reducing the pressure needed to maintain flat alveoli, thereby preventing alveolar collapse (atelectasis).

Respiratory Distress Syndrome (RDS)

• RDS in preterm infants is associated with insufficient surfactant production and/or secretion.
• RDS is a significant cause of neonatal deaths in Western countries.
• Lung maturity of the fetus can be gauged by determining the ratio of DPPC to sphingo-myelin (usually written as the L/S ratio) in amniotic fluid.
• A ratio of two or above indicates lung maturity, reflecting the major shift from sphingomyelin to DPPC synthesis in pneumocytes at approximately 32 weeks of gestation.
• Lung maturation can be accelerated by giving the mother glucocorticoids shortly before delivery.
• Administration of natural or synthetic surfactant can be used in the prevention and treatment of infant RDS.
• RDS can also occur in adults due to insufficient surfactant production in damaged or destroyed surfactant-producing pneumocytes (e.g., from infection or trauma).

Overview of Glycolipids

• Glycolipids are molecules containing both carbohydrate and lipid components.
• Glycolipids are also called glycosphingolipids.
• Glycosphingolipids are essential components of all membranes, but found in greatest amounts in nerve tissue.
• Glycosphingolipids are located in the outer leaflet of the plasma membrane, interacting with the extracellular environment.

Sphingolipidoses

• In a normal individual, the synthesis and degradation of glycosphingolipids are balanced.
• If a specific lysosomal hydrolase required for degradation is missing, a sphingolipid accumulates.
• Lysosomal lipid storage diseases caused by these deficiencies are called sphingolipidoses.
• The result of a specific hydrolase deficiency can dramatically affect nerve tissue, leading to neurological deterioration and potentially early death.

Diagnosis and Treatment

• Sphingolipidoses can be diagnosed measuring enzyme activity in cultured fibroblasts or peripheral leukocytes, or analyzing DNA.
• Histologic examination of the affected tissue is also useful.
• Recombinant human enzyme replacement therapy is a treatment option.

Reference

• Champa, Harvey, and Ferrier (2005), Lippincott's Illustrated Reviews: Biochemistry. (5th/6th edition)

Explore the fascinating world of complex lipid metabolism, focusing on phospholipids and their crucial roles in cell membranes and lung surfactant. Learn about the properties of amphipathic molecules and the specific functions of phosphatidylcholine (PC) in respiratory health.