In yeast as in bacteria, phosphatidylserine can be produced by
condensation of CDP-diacylglycerol and serine, and phosphatidylethanolamine can
be synthesized from phosphatidylserine in the reaction catalyzed by
phosphatidylserine decarboxylase (Fig. 20-25). 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. All three methylation reactions are catalyzed by a single enzyme (a
methyltransferase) with S-adenosylmethionine as the methyl group donor (see Fig.
17-20).
In mammals, phosphatidylserine is not synthesized from CDPdiacylglycerol;
instead, it is derived from phosphatidylethanolamine via the head group exchange
reaction shown in Figure 20-25. In mammals, synthesis of all nitrogen-containing
phospholipids occurs by strategy 2 of Figure 20-22: phosphorylation and
activation of the head group followed by condensation with diacylglycerol. For
example, choline is reused ("salvaged") by being phosphorylated then converted
into CDP-choline by condensation with CTP. A diacylglycerol displaces CMP from
CDP-choline, producing phosphatidylcholine (Fig. 20-26).
An analogous salvage pathway converts ethanolamine obtained in the diet into
phosphatidylethanolamine. In the liver, phosphatidylcholine is also produced by
methylation of phosphatidylethanolamine using S-adenosylmethionine, as described
above. In all other tissues, however, phosphatidylcholine is produced only by
condensation of diacylglycerol and CDP-choline. The pathways to
phosphatidylcholine and phosphatidylethanolamine in various organisms are
summarized in Figure 20-27.
The biosynthetic pathway to ether lipids, including
plasmalogens and the
platelet-activating factor
(see Fig. 9-8), involves the displacement of an esterified fatty acyl
group by a long-chain alcohol to form the ether linkage (Fig. 20-28). Head group
attachment follows, by mechanisms essentially like those for the common
ester-linked phospholipids. Finally, the characteristic double bond of
plasmalogens is introduced by the action of a mixed-function oxidase similar to
that responsible for desaturation of fatty acids (Fig. 20-14).
The biosynthesis of sphingolipids occurs in four stages: (1) synthesis of the
18-carbon amine
sphinganine from palmitoyl-CoA and serine; (2)
attachment of a fatty acid in amide linkage to form ceramide; (3) desaturation
of the sphinganine moiety to form
sphingosine; and (4)
attachment of a head group to produce a sphingolipid such as a
cerebroside or
sphingomyelin (Fig. 20-29). The pathway
shares several features with the pathways leading to glycerophospholipids: NADPH
provides reducing power and fatty acids enter as their activated CoA
derivatives. In cerebroside formation, sugars enter as their activated
nucleotide derivatives. Head group attachment in sphingolipid synthesis has
several novel aspects. Phosphatidylcholine, rather than CDP-choline, serves as
the donor of phosphocholine in the synthesis of sphingomyelin from the ceramide
(Fig. 20-29). In glycolipids, the cerebrosides and
gangliosides
(see Fig. 9-9), the head group is a sugar, attached directly to the C-1 hydroxyl
of sphingosine in glycosidic linkage, rather than through a phosphodiester bond;
the sugar donor is a UDP-sugar (UDP-glucose or UDP-galactose).
After their synthesis on the smooth endoplasmic reticulum, the polar lipids,
including the glycerophospholipids, sphingolipids, and glycolipids, are inserted
into different cell membranes in different proportions. The mechanism by which
specific lipids are targeted for insertion into specific intracellular membranes
is not yet understood. Because membrane lipids are insoluble in water, they
cannot simply diffuse from their point of synthesis (the endoplasmic reticulum)
to their point of insertion. Instead, they are delivered in membrane vesicles
that bud from the Golgi complex then move to and fuse with the target membrane
(see Figs. 2-10, 10-14). There are also cytosolic proteins that bind
phospholipids and sterols and carry them from one cell membrane to another and
from one face of a lipid bilayer to the other. The combined action of transport
vesicles and these proteins (and perhaps other proteins yet to be discovered)
produces the characteristic lipid composition of each organelle membrane
