Lung PDF Biochemistry and Nutrition

Lippincott’s illustrated reviews Chapter 17 – Page 201 Lecture 29 Complex Lipid Metabolism 1  Specific Objectives By the end of this lecture students can be able to: Understand role of Phospholipids in membranes. Explain role of PC in lung surfactant. Di...

Lippincott’s illustrated reviews Chapter 17 – Page 201 Lecture 29 Complex Lipid Metabolism 1  Specific Objectives By the end of this lecture students can be able to: Understand role of Phospholipids in membranes. Explain role of PC in lung surfactant. Discuss sphingolipidoses disease. 2  Overview of phospholipids Like fatty acids, phospholipids are amphipathic in nature. Each has a hydrophilic head (the phosphate group plus whatever alcohol is attached to it, for example, serine, ethanolamine, and choline, and a long, hydrophobic tail (containing fatty acids or fatty acid–derived hydrocarbons. 3  Phospholipids are the predominant lipids of cell membranes. In membranes, the hydrophobic portion of a phospholipid molecule is associated with the nonpolar portions of other membrane constituents, such as glycolipids, proteins, and cholesterol. 4  The hydrophilic (polar) head of the phospholipid extends outward, interacting with the intracellular or extracellular aqueous environment. 5  Membrane phospholipids also function as a reservoir for intracellular messengers, and, for some proteins, phospholipids serve as anchors to cell membranes. Nonmembrane-bound phospholipids serve additional functions in the body, for example, as components of lung surfactant and essential components of bile, where their detergent properties aid in the solubilization of cholesterol. 6  Role of phosphatidylcholine (PC) in lung surfactant In dipalmitoyl - phosphatidylcholine (DPPC, or dipalmitoyl lecithin), positions 1 and 2 on the glycerol are occupied by palmitate. DPPC, made and secreted by Type II pneumocytes, is the major lipid component of lung surfactant—the extracellular fluid layer lining the alveoli. 7  Surfactant serves to decrease the surface tension of this fluid layer, reducing the pressure needed to rein flat alveoli, thereby preventing alveolar collapse (atelectasis). 8 Respiratory distress syndrome (RDS) in preterm infants is associated with insufficient surfactant production and/or secretion, and is a significant cause of all 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 (for lecithin)/S ratio, in amniotic fluid. 9  A ratio of two or above is evidence of maturity, because it reflects the major shift from sphingomyelin to DPPC synthesis that occurs in the pneumocytes at about 32 weeks of gestation. 10  Lung maturation can be accelerated by giving the mother glucocorticoids shortly before delivery. Administration of natural or synthetic surfactant (by intratracheal instillation) is also used in the prevention and treatment of infant RDS. RDS due to an insufficient amount of surfactant can also occur in adults whose surfactant-producing pneumocytes have been damaged or destroyed, for example, by infection or trauma. 11  Overview of glycolipids Glycolipids are molecules that contain both carbohydrate and lipid components. They also called glycosphingolipids. 12  Like the phospholipids, glycosphingolipids are essential components of all membranes in the body, but they are found in greatest amounts in nerve tissue. They are located in the outer leaflet of the plasma membrane, where they interact with the extracellular environment. 13 Function As such, they play a role in the regulation of cellular interactions, growth, and development. Glycosphingo lipids are antigenic, and they have been identified as a source of blood group antigens, various embryonic antigens specific for particular stages of fetal development, and some tumor antigens. They also serve as cell surface receptors for cholera and tetanus toxins, as well as for certain viruses and microbes. 14  Sphingolipidoses In a normal individual, synthesis and degradation of glycosphingolipids are balanced, so that the amount of these compounds present in membranes is constant. If a specific lysosomal hydrolase required for degradation is partially or totally missing, a sphingolipid accumulates. Lysosomal lipid storage diseases caused by these deficiencies are called sphingolipidoses. The result of a specific hydrolase deficiency may be seen dramatically in nerve tissue, where neurologic deterioration 15 can lead to early death. Diagnosis and treatment: A specific sphingolipidosis can be diagnosed by measuring enzyme activity in cultured fibroblasts or peripheral leukocytes, or by analysis of DNA. Histologic examination of the affected tissue is also useful. Treated by recombinant human enzyme replacement therapy 16 Reference Book: Champe, P. C., Harvey, R. A. and Ferrier, D. R., 2005. Biochemistry “Lippincott’s Illustrated Reviews”, 5th or 6th Edition 17