6. METABOLISM OF PHOSPHOLIPIDS
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of the label into the various tissue phospholipids; certain tissues, such
as liver and kidney, are especially active in this respect. As no further
new phospholipid is required for net growth, a rapid turnover of tissue
phospholipids must be occurring to maintain physiological function.
These isotopic incorporation experiments with adult animals not only
indicate that there are active systems for synthesizing phospholipids in
the animals, but also suggest by implication that catabolic systems must
also be present in order to maintain a concentration equilibrium.
I. The Biochemistry of Phospholipid Synthesis
The enzymatic steps in the biosynthesis of phospholipids have been
elucidated only comparatively recently, largely by the use of isotopically
labeled intermediaries. In a notable contribution to the field, Kennedy
and his co-workers have shown that the cytidine nucleotides participate
as specific coenzymes. While it is apparent that this cytidine nucleotidecatalyzed type of synthesis must be a major source of the phospholipids
that occur in living things, it remains to be seen whether any of the
phospholipids are synthesized by other metabolic pathways e.g., via
lysophospholipid (2a).
The chemistry of the biosynthesis of lecithin, phosphatidyl ethanolamine, plasmalogen, and sphingomyelin are conveniently dealt with together, as the pathways involved show many similarities. It must be
emphasized, however, that although analogous chemical reactions occur
for each lipid, the enzymes involved are usually quite different.
The reactions involved are shown in Fig. 1.
A. BIOSYNTHESIS OF CYTIDINE DIPHOSPHATE-"BASE" INTERMEDIATE
For each lipid the starting point of the synthesis is the phosphorylation of choline or ethanolamine by adenosine triphosphate (ATP) catalyzed by an enzyme which has been called choline phosphokinase (3).
The enzyme has been purified 25-fold with an autolyzate of brewers'
yeast as a starting material. It requires Mg
2+ for its activity, and it is
able to catalyze the phosphorylation both of choline and ethanolamine,
but not serine.
The phosphorylcholine and phosphorylethanolamine formed in these
reactions can react with cytidine triphosphate, giving cytidine diphosphate choline or cytidine diphosphate ethanolamine, respectively, and
inorganic pyrophosphate. The catalysis of this freely reversible step is
brought about by two separate enzymes, phosphorylcholine cytidyl
transf erase and phosphorylethanolamine cytidyl transf erase (6). These
are widely distributed in nature (Table I). The phosphorylcholine
cytidyl transferase is an "insoluble" enzyme. It is completely specific for
267
of the label into the various tissue phospholipids; certain tissues, such
as liver and kidney, are especially active in this respect. As no further
new phospholipid is required for net growth, a rapid turnover of tissue
phospholipids must be occurring to maintain physiological function.
These isotopic incorporation experiments with adult animals not only
indicate that there are active systems for synthesizing phospholipids in
the animals, but also suggest by implication that catabolic systems must
also be present in order to maintain a concentration equilibrium.
I. The Biochemistry of Phospholipid Synthesis
The enzymatic steps in the biosynthesis of phospholipids have been
elucidated only comparatively recently, largely by the use of isotopically
labeled intermediaries. In a notable contribution to the field, Kennedy
and his co-workers have shown that the cytidine nucleotides participate
as specific coenzymes. While it is apparent that this cytidine nucleotidecatalyzed type of synthesis must be a major source of the phospholipids
that occur in living things, it remains to be seen whether any of the
phospholipids are synthesized by other metabolic pathways e.g., via
lysophospholipid (2a).
The chemistry of the biosynthesis of lecithin, phosphatidyl ethanolamine, plasmalogen, and sphingomyelin are conveniently dealt with together, as the pathways involved show many similarities. It must be
emphasized, however, that although analogous chemical reactions occur
for each lipid, the enzymes involved are usually quite different.
The reactions involved are shown in Fig. 1.
A. BIOSYNTHESIS OF CYTIDINE DIPHOSPHATE-"BASE" INTERMEDIATE
For each lipid the starting point of the synthesis is the phosphorylation of choline or ethanolamine by adenosine triphosphate (ATP) catalyzed by an enzyme which has been called choline phosphokinase (3).
The enzyme has been purified 25-fold with an autolyzate of brewers'
yeast as a starting material. It requires Mg
2+ for its activity, and it is
able to catalyze the phosphorylation both of choline and ethanolamine,
but not serine.
The phosphorylcholine and phosphorylethanolamine formed in these
reactions can react with cytidine triphosphate, giving cytidine diphosphate choline or cytidine diphosphate ethanolamine, respectively, and
inorganic pyrophosphate. The catalysis of this freely reversible step is
brought about by two separate enzymes, phosphorylcholine cytidyl
transf erase and phosphorylethanolamine cytidyl transf erase (6). These
are widely distributed in nature (Table I). The phosphorylcholine
cytidyl transferase is an "insoluble" enzyme. It is completely specific for