section 19 2
Phospholipids and Glycosphingolipids in Clinical Medicine
407
o
o
II
II
H3C — (C H 2)— C H — C H — C — S C o A
+
H O — c — C H — C H 2O H
nh2
P a lm ito y l-C o A
l - S e r in e
..
.
. ^
A
3 -O x o s p h in g a n in e
(from s e rin e ) C 0
2
s v n th a s e to v rid o x a
C o A
s y n th a s e (p ÿ rid o x al p h o s p h a te )
H
3
C — (C H
2
) — C H — C H ^ - C — C H — C H 2O H
NHj
3 -O x o s p h in g a n in e
r
N A D PH + H
O x id o re d u c ta s e
V*NADP+
HjC— (CH,)— CH— CH— CH— CH— CH2OH
~
OH
nh2
R — C — S C o A
N -A c y ltra n s fe ra se
C o A S H
H
3
C — (CH
2
),— C H — C H — C H — C H — C H 2O H
O H
NH
I
c=o
R
N -A c y lsp h in g an in e
O x id iz e d flavin e n z y m e ^
R e d u c e d flavin e n z y m e
S p h in g a n in e
O x id iz e d flavin e n z y m e
R e d u c e d flavin e n z y m e „
H
0
H3c—
(C H 2)— c = c — C H — Ç H — C H 2O H
H
O H
n h
2
S p h in g o s in e (4 -tra n s-D -sp h in g e n in e )
O
^ R — C — S C o A
N -A c y ltra n s fe ra s e
C o A S H
H
H3C— (CHj,)— C = Ç— CH— CH2— CH2OH
H
OH
NH
0=0
N -A c y lsp h in g o sin e
|
(c e ra m id e )
r
FIGURE 19-7
Biosynthesis of sphingosine and ceramide.
After synthesis in the various compartments of en-
doplasmic reticulum of alveolar type II cells, surfactant
components are assembled in the cytosol into lamel-
lar bodies. In the process of formation of lamellar bod-
ies, the transfer of phospholipids between membranes
is facilitated by phospholipid transfer proteins, which
are nonenzymatic proteins found in all eukaryotic cells
and which play an important role in lipid metabolism.
There are three well-characterized phospholipid transfer
proteins:
1. PC-specific transfer protein.
2. PI- and PC-specific transfer protein.
3. Phospholipids and cholesterol-nonspecific lipid
transfer protein (also known as sterol carrier protein).
All three of these proteins are present in the lung. The
lamellar bodies are secreted into alveolar lumen where
they are transformed into an extracellular form of surfac-
tant that has a quadratic lattice structure called
tubular
myelin.
The three-dimensional tubulin-myelin structures
spread in a monolayer at the air-liquid interface. This
spreading decreases the surface tension, prevents alveolar
collapse at the end of expiration, and confers mechanical
stability to the alveoli. The surfactant system is in a con-
tinuous state of flux, and surfactant is recycled by uptake
