section 19.1
Phospholipids
405
phosphatidylinositol content greatly exceeds that of the
other two. The activity of a number of hormones, growth
factors, and neurotransmitters depends upon hydrolysis of
phosphatidylinositol 4,5-bisphosphate to inositol triphos-
phate and diacylglycérol, which serve to initiate parallel
metabolic cascades that can mobilize intracellular calcium
stores, activate protein kinase C and release arachidonic
acid. Each of these events in turn can regulate a number
of cellular processes (Chapter 30).
The transfer of phosphatidic acid from CDP-diacylgly-
cerol to phosphatidylglycerol yields diphosphatidylglyc-
erol, orcardiolipin (Figure 19-4), which is found in highest
concentration in the inner membranes of mitochondria of
cardiac muscle. Cardiolipin isolated from beef heart is
used as an antigen in serological flocculation and precip-
itation tests for syphilis, a sexually transmitted disease
caused by
Treponema pallidum.
Anticardiolipin antibod-
ies are formed in response to lipoidal material released
from damaged host cells early in the infection and that
present on the cell surface of the treponeme. This test is
nonspecific. In a specific test for syphilis, antigen derived
from
T pallidum
itself is used to detect the presence of
antibodies specific to it.
In the synthesis of phosphatidic acid, the starting ma-
terial may be glycerol, or dihydroxyacetone phosphate, a
product of aldolase action on fructose-
1
,
6
-bisphosphate
(Chapter 13). Analogous reactions are used in the synthe-
sis of plasmalogens, which, like phosphoglycerides, have
the common glycerol backbone. However, at the Q posi-
tion, an a,/l-unsaturated fatty ether is present rather than
a fatty acid ester:
H /
h
CIS
H C — O — C = C — R
I
R — C — O — C — H
- U n s a t u r a t e d fa tty e th e r
II
0
O
II
♦
H
2
C — O — P — 0 — C H
2
— C H 2— N (C H
3)3
c r
1-A lkyl-2-acyl-sn -glycero-3-p h osp h orylch olin e
(p h o sp h a tid a lch o lin e, a p la sm a lo g en )
The a,/3-unsaturated fatty ether is an aldehydogenic group
because its hydrolysis releases an
a,ft
-unsaturated primary
alcohol that readily tautomerizes to an aldehyde. Choline,
ethanolamine, and serine plasmalogens are found in car-
diac and skeletal muscle, brain, and liver. The biosynthesis
of phosphatidylethanolamine is shown in Figure 19-5.
o
H2C O H
c = o
R C O S C o A
C oA
H2C— O— C — R
c = o
R 'C H
2
C H 2O H
r c o o
V - Mq2 C 9
H2c o p o r
D ih y d ro x y aceto n e
p h o s p h a te
H2c o p o r
1 -A cy ld ih y d ro x y aceto n e
p h o s p h a te
H
2
C — O — CH
2
CH
2
R '
q —
q
1 -A lkyldihydroxy-
|
a c e to n e p h o s p h a te
H2c o p o r
■NADPH + H +
K
— N A D P +
O
H2C — O — C K C H .R '
Il
I
R — C — O — C O
^
C4M P C D P -
e th a n o lam in e
K C O P O C K C K N H ,
sn
-1-A lkyI-2-acylgIyceryl-
3 -p h o s p h o e th a n o la m in e
O
K C — o — C K C K R -
Il
I
R — C — O — CH
I
CHjOH
s /
7-1
-A lkyl-2-acylglycerol
Q , N A D PH
O
H2C — O — C H = C H R '
Il
I
R — C — O — Ç O
DPC
L
o
E th an o la m in e p la sm a lo g e n
t^ C — O — C H
2
CH
2
R '
H O — CH
H2copor
sn-1-A lkylglyceryl-
3 -p h o s p h a te
p
R 'C O S C o A
4
^CoA
R — C — O — CH
H .C 0 P 0 3 -
sn -1 -A lkyl-2-acylglyceryl-3-
p h o s p h a te
FIGURE 19-5
Biosynthesis of ethanolamine plasmalogen. Enzymes: (1) acyltransferase; (2) synthase; (3) oxidoreductase;
(4) acyltransferase; (5) phosphatase; (6) transferase; (7) A1-alkyl desaturase.
