6. METABOLISM OF PHOSPHOLIPIDS
269
cytidine triphosphate and it requires a divalent ion such as Mg
2+ or
Mn
2+ for full activity.
B. LECITHIN AND PHOSPHATIDYLETHANOLAMINE BIOSYNTHESIS
The synthesis of lecithin and phosphatidylethanolamine from these
cytidine-containing intermediaries (cytidine diphosphate choline and
cytidine diphosphate ethanolamine) is brought about by the transfer
of the phosphorylated base unit to a D-l,2-diglyceride with the release
of cytidine monophosphate. Again two different enzymes are responsible [phosphorylcholine glyceride transferase and phosphorylethanolamine glyceride transf erase (6)]. The reactions are again reversible
(10); they require Mg
2+ or Mn
2+ but are completely inhibited by low
concentrations of Ca
2+ (10
3 M). The presence of a surface active agent,
e.g., bile salts, digitonin, or Tween 20, stimulates the lecithin synthesis
ten to twentyfold probably by removing diglyceride from the surface
of the enzyme. Phosphorylcholine glyceride transferase is highly specific for cytidine diphosphate choline, and analogous compounds containing uridine, guanine, and adenosine are quite ineffective in the
system. It appears, however, that deoxycytidine diphosphate choline
and deoxycytidine diphosphate ethanolamine can also be used for the
synthesis of lecithin or phosphatidylethanolamine (19).
C. FORMATION OF D-1,2-DIGLYCERIDE AND PHOSPHATIDIC ACID
It now seems likely that the formation of the D-l,2-diglyceride required as an acceptor for the phosphorylcholine or phosphorylethanolamine units is produced by the dephosphorylation of phosphatidic acid.
The phosphatase that brings about this hydrolysis has a specific action
on phosphatidic acid (12). It appears to be bound in particulate matter
and is inhibited by Mg
2+ and other divalent ions, which probably form
insoluble salts with the substrate. The phosphatidic acid required for
the formation of D-l,2-diglyceride is itself formed from L-a-glycerophosphoric acid. The glycerophosphoric acid required can be formed either
by the enzyme glycerophosphate dehydrogenase utilizing the glycolysis
intermediary dihydroxyacetone phosphate as precursor or by the direct
phosphorylation of glycerol by ATP or uridine triphosphate (UTP)
catalyzed by the enzyme glycerokinase (14, 15). This latter enzyme
has now been crystallized; it requires Mg
2+ or Mn
2+ for activity. The
formation of phosphatidic acid from the glycerophosphate is brought
about by an enzyme system that is present in liver particles and catalyzes the transfer of two fatty acids from coenzyme A (16). At present
the mechanism of the acylation is not known, and it is possible that
there is a stepwise addition of the two acyl groups on the vacant
269
cytidine triphosphate and it requires a divalent ion such as Mg
2+ or
Mn
2+ for full activity.
B. LECITHIN AND PHOSPHATIDYLETHANOLAMINE BIOSYNTHESIS
The synthesis of lecithin and phosphatidylethanolamine from these
cytidine-containing intermediaries (cytidine diphosphate choline and
cytidine diphosphate ethanolamine) is brought about by the transfer
of the phosphorylated base unit to a D-l,2-diglyceride with the release
of cytidine monophosphate. Again two different enzymes are responsible [phosphorylcholine glyceride transferase and phosphorylethanolamine glyceride transf erase (6)]. The reactions are again reversible
(10); they require Mg
2+ or Mn
2+ but are completely inhibited by low
concentrations of Ca
2+ (10
3 M). The presence of a surface active agent,
e.g., bile salts, digitonin, or Tween 20, stimulates the lecithin synthesis
ten to twentyfold probably by removing diglyceride from the surface
of the enzyme. Phosphorylcholine glyceride transferase is highly specific for cytidine diphosphate choline, and analogous compounds containing uridine, guanine, and adenosine are quite ineffective in the
system. It appears, however, that deoxycytidine diphosphate choline
and deoxycytidine diphosphate ethanolamine can also be used for the
synthesis of lecithin or phosphatidylethanolamine (19).
C. FORMATION OF D-1,2-DIGLYCERIDE AND PHOSPHATIDIC ACID
It now seems likely that the formation of the D-l,2-diglyceride required as an acceptor for the phosphorylcholine or phosphorylethanolamine units is produced by the dephosphorylation of phosphatidic acid.
The phosphatase that brings about this hydrolysis has a specific action
on phosphatidic acid (12). It appears to be bound in particulate matter
and is inhibited by Mg
2+ and other divalent ions, which probably form
insoluble salts with the substrate. The phosphatidic acid required for
the formation of D-l,2-diglyceride is itself formed from L-a-glycerophosphoric acid. The glycerophosphoric acid required can be formed either
by the enzyme glycerophosphate dehydrogenase utilizing the glycolysis
intermediary dihydroxyacetone phosphate as precursor or by the direct
phosphorylation of glycerol by ATP or uridine triphosphate (UTP)
catalyzed by the enzyme glycerokinase (14, 15). This latter enzyme
has now been crystallized; it requires Mg
2+ or Mn
2+ for activity. The
formation of phosphatidic acid from the glycerophosphate is brought
about by an enzyme system that is present in liver particles and catalyzes the transfer of two fatty acids from coenzyme A (16). At present
the mechanism of the acylation is not known, and it is possible that
there is a stepwise addition of the two acyl groups on the vacant