Biosynthesis of Triacylglycerols:- Eukaryotic Pathways to Phosphatidylserine, Phosphatidylethanolamine, and Phosphatidylcholine Are Interrelated
Yeast, like bacteria, can produce phosphatidylserine by condensation of CDP-diacylglycerol and serine, and can synthesize phosphatidylethanolamine from phosphatidyl serine in the reaction catalyzed by phosphatidylserine decarboxylase (Fig. 21–27). In mammalian cells, an alternative route to phosphatidylserine is a head-group exchange reaction, in which free serine displaces ethanolamine. Phosphatidylethanolamine may also be converted to phosphatidylcholine(lecithin) by the addition of three methyl groups to its amino group; S adenosylmethionine is the methyl group donor (see Fig. 18–18) for all three methylation reactions. In mammals, phosphatidylserine is not synthesized from CDP-diacylglycerol; instead, it is derived from phosphatidylethanolamine via the head-group exchange reaction (Fig. 21–27). Synthesis of phosphatidylethan olamine and phosphatidylcholine in mammals occurs by strategy 2 of Figure 21–24: phosphorylation and activation of the head group, followed by condensation with diacylglycerol. For example, choline is reused (“salvaged”) by being phosphorylated then converted to CDP-choline by condensation with CTP. A diacylglycerol displaces CMP from CDP-choline, producing phosphatidylcholine (Fig. 21–28). An analogous salvage pathway converts ethanolamine obtained in the diet to phosphatidylethanolamine. In the liver, phos phatidylcholine is also produced by methylation of phosphatidylethanolamine (with S-adenosylmethionine, as described above), but in all other tissues phos phatidylcholine is produced only by condensation of diacylglycerol and CDP-choline. The pathways to phosphatidylcholine and phosphatidylethanolamine in various organisms are summarized in Figure 21–29.
Although the role of lipid composition in membrane function is not entirely understood, changes in composition can produce dramatic effects. Researchers have isolated fruit flies with mutations in the gene that en codes ethanolamine kinase (analogous to choline kinase; Fig. 21–28). Lack of this enzyme eliminates one path way for phosphatidylethanolamine synthesis, thereby reducing the amount of this lipid in cellular membranes. Flies with this mutation—those with the genotype easily shocked—exhibit transient paralysis following electrical stimulation or mechanical shock that would not affect wild-type flies.
FIGURE 21–27 The “salvage” pathway from phosphatidylserine to phosphatidylethanolamine and phosphatidylcholine in yeast. Phosphatidylserine and phosphatidylethanolamine are interconverted by a reversible head-group exchange reaction. In mammals, phosphatidylserine is derived from phosphatidylethanolamine by a reversal of this reaction; adoMet is S-adenosylmethionine; adoHcy, S-adenosylhomocysteine.
FIGURE 21–28 Pathway for phosphatidylcholine synthesis from choline in mammals. The same strategy shown here (strategy 2 in Fig. 21–24) is also used for salvaging ethanolamine in phosphatidylethanolamine synthesis.
FIGURE 21–29 Summary of the pathways to phosphatidylcholine and phosphatidylethanolamine. Conversion of phosphatidylethanolamine to phosphatidylcholine in mammals takes place only in the liver.
