20
F. B. SHORLAND
reduced diphosphopyridine nucleotide (DPNH) derived from the breakdown of carbohydrate. A high concentration of these substrates must
be maintained, and the concentration of free CoA kept low, if the
equilibria of ß-ketothiolase and of ß-ketoreductase are to be shifted in
the direction of synthesis.
It appears that the complex enzyme system that catalyzes the oxidative degradation, but not the synthesis, of fatty acids is localized in the
mitochondria of the liver cell and that the particle-free soluble extracts
of the liver and mammary gland, when properly supplemented, catalyze
the synthesis of fatty acids [cf. Kennedy (106)].
The synthesis of glycerides and phospholipids may now be considered. Kornberg and Pricer (104, 107) found that the sediment of the
liver homogenate of the guinea pig possessed an enzyme capable of
synthesizing the phosphatidic acids from acyl CoA and a-glycerophosphoric acid (4).
H 2 · C · OH
H 2 CO · COR
2R · CO · S · CoA + H·C·OH
-> 2HS · CoA + H · CO · COR
I
I
Ho · COPO3H0.
H 2 CO · P0 3 H 2
(4)
This enzyme has a distinct optimum with coenzyme A derivatives
of Ci6—Ci8 acids. The preferential occurrence of Ci 6 —Ci 8 acids in the
body might thus be explained.
Phosphatidic acids are not found in fresh tissues, probably owing to
their rapid dephosphorylation to form orthophosphate and D-l,2-diglyceride. An enzyme concerned with this reaction was shown to be present
in chicken liver(108). The D-l,2-diglyceride thus produced may then
react with a long-chain fatty ester of CoA to form triglyceride, as
described above, or else react with cytidine diphosphate choline to form
lecithin (109), or cytidine diphosphate ethanolamine to form phosphatidyl ethanolamine (110).
Sphingomyelin is similarly formed by the transfer of the phosphorylcholine moiety of cytidine diphosphate choline to the free primary
hydroxyl group of lignocerylsphingosine (111). On the other hand, inositol phosphatides are considered to result from the reaction of cytidine
diphosphate D-a,/?-digrycerides with the hydroxyl group of inositol (112).
The close link between the synthesis of glycerides and phospholipids
is thus established, and it may be anticipated that phospholipids and
triglycerides in the same tissues will have similar fatty acid compositions. As will be later mentioned (Section V), however, the distribution
of the types of fatty acids between glyceride and phospholipids and
between phospholipid species shows widely different patterns. There is
F. B. SHORLAND
reduced diphosphopyridine nucleotide (DPNH) derived from the breakdown of carbohydrate. A high concentration of these substrates must
be maintained, and the concentration of free CoA kept low, if the
equilibria of ß-ketothiolase and of ß-ketoreductase are to be shifted in
the direction of synthesis.
It appears that the complex enzyme system that catalyzes the oxidative degradation, but not the synthesis, of fatty acids is localized in the
mitochondria of the liver cell and that the particle-free soluble extracts
of the liver and mammary gland, when properly supplemented, catalyze
the synthesis of fatty acids [cf. Kennedy (106)].
The synthesis of glycerides and phospholipids may now be considered. Kornberg and Pricer (104, 107) found that the sediment of the
liver homogenate of the guinea pig possessed an enzyme capable of
synthesizing the phosphatidic acids from acyl CoA and a-glycerophosphoric acid (4).
H 2 · C · OH
H 2 CO · COR
2R · CO · S · CoA + H·C·OH
-> 2HS · CoA + H · CO · COR
I
I
Ho · COPO3H0.
H 2 CO · P0 3 H 2
(4)
This enzyme has a distinct optimum with coenzyme A derivatives
of Ci6—Ci8 acids. The preferential occurrence of Ci 6 —Ci 8 acids in the
body might thus be explained.
Phosphatidic acids are not found in fresh tissues, probably owing to
their rapid dephosphorylation to form orthophosphate and D-l,2-diglyceride. An enzyme concerned with this reaction was shown to be present
in chicken liver(108). The D-l,2-diglyceride thus produced may then
react with a long-chain fatty ester of CoA to form triglyceride, as
described above, or else react with cytidine diphosphate choline to form
lecithin (109), or cytidine diphosphate ethanolamine to form phosphatidyl ethanolamine (110).
Sphingomyelin is similarly formed by the transfer of the phosphorylcholine moiety of cytidine diphosphate choline to the free primary
hydroxyl group of lignocerylsphingosine (111). On the other hand, inositol phosphatides are considered to result from the reaction of cytidine
diphosphate D-a,/?-digrycerides with the hydroxyl group of inositol (112).
The close link between the synthesis of glycerides and phospholipids
is thus established, and it may be anticipated that phospholipids and
triglycerides in the same tissues will have similar fatty acid compositions. As will be later mentioned (Section V), however, the distribution
of the types of fatty acids between glyceride and phospholipids and
between phospholipid species shows widely different patterns. There is