Significance of choline reutilization: The reutilization of choline is important because, although humans can synthesize choline de novo, the amount made is insufficient for our needs. Thus, choline is an essential dietary nutrient with an adequate intake (see p. 358) of 550 mg for men and 425 mg for women. [Note: Choline is also used for the synthesis of acetylcholine, a neurotransmitter.] b.
Phosphatidylcholine in lung surfactant: The pathway described above is the principal pathway for the synthesis of dipalmitoylphosphatidylcholine (DPPC or, dipalmitoyl lecithin). In DPPC, positions 1 and 2 on the glycerol are occupied by palmitate, a saturated LCFA. DPPC, made and secreted by type II pneumocytes, is a major lipid component of lung surfactant, which is the extracellular fluid layer lining the alveoli. Surfactant serves to decrease the surface tension of this fluid layer, reducing the pressure needed to reinflate alveoli, thereby preventing alveolar collapse (atelectasis). [Note: Surfactant is a complex mixture of lipids (90%) and proteins (10%), with DPPC being the major component for reducing surface tension.]
Fetal lung maturity can be gauged by determining the DPPC/sphingomyelin ratio, usually written as L (for lecithin)/S, in amniotic fluid. A value ≥2 is evidence of maturity, because it reflects the shift from sphingomyelin to DPPC synthesis that occurs in pneumocytes at ~32 weeks’ gestation.
c. Lung maturity: 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 maturation can be accelerated by giving the mother glucocorticoids shortly before delivery to induce expression of specific genes. Postnatal administration of natural or synthetic surfactant (by intratracheal instillation) is also used. [Note: Acute RDS, seen in all age groups, is the result of alveolar damage (due to infection, injury, or aspiration) that causes fluid to accumulate in the alveoli, impeding the exchange of oxygen (O2) and carbon dioxide (CO2).] 2. Phosphatidylcholine synthesis from phosphatidylserine: The liver requires a mechanism for producing PC, even when free choline levels are low, because it exports significant amounts of PC in the bile and as a component of plasma lipoproteins. To provide the needed PC, PS is decarboxylated to PE by PS decarboxylase. PE then undergoes three methylation steps to produce PC, as illustrated in Figure 17.6. Sadenosylmethionine is the methyl group donor (see p. 264).
C. Phosphatidylserine
PS synthesis in mammalian tissues is provided by the base exchange reaction, in which the ethanolamine of PE is exchanged for free serine (see Fig. 17.6). This reaction, although reversible, is used primarily to produce the PS required for membrane synthesis. PS has a net negative charge. (See online Chapter 35 for the role of PS in clotting.)
D. Phosphatidylinositol