402
chapter 19
Lipids II: Phospholipids, Glycosphingolipids, and Cholesterol
C H
2
— o — C —
R '
O
R — C — O — C H
O
C H — P — O —
-<
O-
-C H
2
C H j N (C H 3)
P h o s p h a tid y lc h o lin e
— C H C H j N H j P h o s p h a tid y le th a n o la m in e
N H
3
— C H
2
C H —
C O O
P h o s p h a tid y ls e rin e
O H
1'
12'
3'
— C H
2
— C — C H 2O H
P h o sp h a tid y lg ly c e ro l
O H
- O H P h o s p h a tid y lin o s ito l
FIGURE 19-1
Structure of some glycerophospholipids.
phosphatidylcholine biosynthesis uses cytidine diphos-
phate (CDP) choline (Figure 19-2). Many reactions of
phospholipid synthesis occur in the endoplasmic retic-
ulum. Choline is first phosphorylated by ATP to phos-
phocholine,
which
reacts
with CTP to form CDP-
choline, from which phosphocholine is transferred to
sn-
1,2-diacylglycerol. The rate-limiting step in this path-
way appears to be that catalyzed by CTP:phospho-
choline cytidylyltransferase, which is activated by fatty
acids.
Phosphatidylcholine can also be synthesized by the
méthylation pathway that converts phosphatidylethanol-
amine to phosphatidylcholine, principally in the liver.
The methyl donor is S-adenosylmethionine (Chapter 17).
Phosphatidylethanolamine-N-methyltransferase transfers
three methyl
groups
in
sequence to produce phos-
phatidylcholine. The fatty acid components of phosphati-
dylcholine can then be altered by deacylation-reacylation
reactions.
Phosphatidylcholine is degraded by phospholipases
that cleave preferentially at specific bonds (Chapter 18).
Choline released is phosphorylated by choline kinase and
reutilized in phosphatidylcholine synthesis. However, in
liver mitochondria, choline is also oxidized to betaine
(N-trimethylglycine):
N(CH3)3— CH 2— CH 2OH
Choline
___ NAD’
C h o lin e d eh yd rogen ase
^NA D H + H*
N{CH3)3— C H 2— CHO
Betaine aldehyde
Betaine aldehyde
-•NAD*
B etain e ald e h yd e d eh yd rogen ase
NADH + H*
N(CH3)3— CH 2— CO O "
(Betaine)
Betaine functions as a methyl donor (e.g., in methionine
biosynthesis from homocysteine; Chapter 17), and it can
also be converted to glycine.
Other Glycerophospholipids
Phosphatidylethanolamines,
or cephalins (so-called be-
cause they were first obtained from brain tissue), can
be
synthesized
by reactions
analogous
to
those of
de novo
synthesis of phosphatidylcholine. Ethanolamine
is first phosphorylated by ATP and ethanolamine kinase
to phosphoethanolamine, which then reacts with CTP
to form CDP-ethanolamine. CTP:phosphoethanolamine
cytidylyltransferase is not located on the endoplasmic
reticulum, nor do fatty acids activate it as they do
the analogous enzyme of phosphatidylcholine synthesis.
Finally, 1,2-diacylglycerol phosphoethanolamine trans-
ferase catalyses the reaction of diacylglycerol with CDP-
ethanolamine to form phosphatidylethanolamine.
E t h a n o l a m i n e
^-ATP
8*adp
P h o s p h o e t h a n o l a m i n e
^CTP
^pp,
C D P - e t h a n o l a m i n e
Diacylglycérol
CMP
P h o s p h a t i d y l e t h a n o l a m i n e
