270
R. M. C. DAWSON
hydroxyl groups of the glycerol. In brain tissue, phosphatidic acid can
be synthesized both by the acylation of glycerophosphate and also by
the direct phosphorylation of a diglyceride by ATP (13). It is clear
from Fig. 1, however, that this latter reaction cannot play a part in the
net synthesis of lecithin or phosphatidylethanolamine.
D. SPHINGOMYELIN BIOSYNTHESIS
Sphingomyelin can be synthesized by chicken liver preparations
through an enzyme that catalyzes the transfer of phosphorylcholine
from cytidine diphosphate choline to a ceramide with the elimination
of cytidine monophosphate (18). This reaction brought about by the
enzyme phosphorylcholine ceramide transferase, is analogous to the
transfer of phosphorylcholine to diglyceride in the synthesis of lecithin.
The enzyme responsible differs, however, in that it requires Mn
2+ for
maximum activity.
The best ceramide acceptor is N-acetylsphingosine, and activity of
the transferase decreases as the chain length of the acyl group is increased. However, in the presence of an emulsifying agent (Tween 20)
the activity increases up to a maximum with eight carbon atoms in the
chain length: with chain lengths longer than twelve, activity is found
only if unsaturated bonds are present to assist the emulsification (e.g.,
N-oleyl and N-linoleyl sphingosine). A curious property of the enzyme
system is that it appears to be specific for ceramides with the threo
configuration whereas the ceramides present in sphingomyelin isolated
from tissues have the ertfihro configuration. The sphingomyelin which
has been synthesized in vitro has the threo configuration, so clearly
there is some difference between the synthesis of sphingomyelin in vitro
and in vivo. Possibly in tissues an enzyme may be present that can interconvert threo- and ert^/iro-sphingomyelin.
E. PLASMALOGEN BIOSYNTHESIS
Although the mechanism of the biosynthesis of choline and ethanolamine plasmalogen has not yet been elucidated, there is good evidence
that it is analogous to that of lecithin and phosphatidylethanolamine.
The synthesis is stimulated by the presence of cytidine triphosphate
and glycerophosphate (20), and recently Kiyasu and Kennedy (20a)
have found that a plasmal monoglyceride can act as an acceptor for the
phosphorylcholine unit from cytidine diphosphate choline, using an
enzyme obtained from rat liver. The plasmal monoglyceride used in
these experiments was prepared by hydrolysis of a plasmalogen-rich lecithin fraction with Clostridium perfringens (welchii) phospholipase C
to remove the phosphorylcholine moiety, followed by the separation of
R. M. C. DAWSON
hydroxyl groups of the glycerol. In brain tissue, phosphatidic acid can
be synthesized both by the acylation of glycerophosphate and also by
the direct phosphorylation of a diglyceride by ATP (13). It is clear
from Fig. 1, however, that this latter reaction cannot play a part in the
net synthesis of lecithin or phosphatidylethanolamine.
D. SPHINGOMYELIN BIOSYNTHESIS
Sphingomyelin can be synthesized by chicken liver preparations
through an enzyme that catalyzes the transfer of phosphorylcholine
from cytidine diphosphate choline to a ceramide with the elimination
of cytidine monophosphate (18). This reaction brought about by the
enzyme phosphorylcholine ceramide transferase, is analogous to the
transfer of phosphorylcholine to diglyceride in the synthesis of lecithin.
The enzyme responsible differs, however, in that it requires Mn
2+ for
maximum activity.
The best ceramide acceptor is N-acetylsphingosine, and activity of
the transferase decreases as the chain length of the acyl group is increased. However, in the presence of an emulsifying agent (Tween 20)
the activity increases up to a maximum with eight carbon atoms in the
chain length: with chain lengths longer than twelve, activity is found
only if unsaturated bonds are present to assist the emulsification (e.g.,
N-oleyl and N-linoleyl sphingosine). A curious property of the enzyme
system is that it appears to be specific for ceramides with the threo
configuration whereas the ceramides present in sphingomyelin isolated
from tissues have the ertfihro configuration. The sphingomyelin which
has been synthesized in vitro has the threo configuration, so clearly
there is some difference between the synthesis of sphingomyelin in vitro
and in vivo. Possibly in tissues an enzyme may be present that can interconvert threo- and ert^/iro-sphingomyelin.
E. PLASMALOGEN BIOSYNTHESIS
Although the mechanism of the biosynthesis of choline and ethanolamine plasmalogen has not yet been elucidated, there is good evidence
that it is analogous to that of lecithin and phosphatidylethanolamine.
The synthesis is stimulated by the presence of cytidine triphosphate
and glycerophosphate (20), and recently Kiyasu and Kennedy (20a)
have found that a plasmal monoglyceride can act as an acceptor for the
phosphorylcholine unit from cytidine diphosphate choline, using an
enzyme obtained from rat liver. The plasmal monoglyceride used in
these experiments was prepared by hydrolysis of a plasmalogen-rich lecithin fraction with Clostridium perfringens (welchii) phospholipase C
to remove the phosphorylcholine moiety, followed by the separation of