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J. Biol. Chem., Vol. 263, Issue 34, 18078-18085, 12, 1988
Regulation of phospholipid biosynthesis in Saccharomyces cerevisiae by inositol. Inositol is an inhibitor of phosphatidylserine synthase activity
MJ Kelley, AM Bailis, SA Henry and GM Carman
Department of Food Science, Cook College, Rutgers University, New Brunswick, 08903.
The addition of inositol to the growth medium of Saccharomyces cerevisiae
resulted in rapid changes in the rates of phospholipid biosynthesis. The
partitioning of the phospholipid intermediate CDP- diacylglycerol was
shifted to phosphatidylinositol at the expense of phosphatidylserine and
its derivatives phosphatidylethanolamine and phosphatidylcholine. Serine at
133-fold greater concentrations than that of inositol shifted the
partitioning of CDP-diacylglycerol to phosphatidylserine at the expense of
phosphatidylinositol but to a much lesser degree. Kinetic experiments with
pure phosphatidylserine synthase and phosphatidylinositol synthase
indicated that the partitioning of CDP-diacylglycerol between
phosphatidylserine and phosphatidylinositol was not governed by the
affinities both enzymes have for their common substrate CDP-diacylglycerol.
Instead, the main regulation of phosphatidylinositol and phosphatidylserine
synthesis was through the exogenous supply of inositol. The Km of inositol
(0.21 mM) for phosphatidylinositol synthase was 9-fold higher than
cytosolic concentration of inositol (24 microM). The Km of serine (0.83 mM)
for phosphatidylserine synthase was 3-fold below the cytosolic
concentration of serine (2.6 mM). Therefore, inositol supplementation
resulted in a dramatic increase in the rate of phosphatidylinositol
synthesis, whereas serine supplementation resulted in little affect on the
rate of phosphatidylserine synthesis. Inositol also contributed to the
regulation of phosphatidylinositol and phosphatidylserine synthesis by
having a direct affect on phosphatidylserine synthase activity. Kinetic
experiments with pure phosphatidylserine synthase showed that inositol was
a noncompetitive inhibitor of the enzyme with a Ki of 65 microM.

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Copyright © 1988 by the American Society for Biochemistry and Molecular Biology.
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