Biosynthesis of phosphatidylserine in rat brain microsomes.

1. Rat brian microsomes incorporated L-serine into phosphatidylserine in the presence of 2mM ATP. This reaction was stimulated 2-fold by the addition of phosphatidic acid (0.2 mM) and 5-fold by the addition of nickel (0.5 mM). 2. This phosphatidylserine synthesis was inhibited completely by p-hydroxymercuribenzoate (0.1 mM) and N-ethylmaleimide (1 mM), whereas the Ca2+-dependent phosphatidylserine synthesis was unaffected by these sulfhydryl reagents. 3. The specific activity of the ATP-Ni2+-dependent phosphatidylserine was increased more than 2-fold during active myelination, whereas the Ca2+-dependent system remained unchanged. 4. Preliminary data indicate that pyrophosphatidic acid (p,p'-bis(1,2-diacyl-sn-glycero-3-)pyrophosphate) is the immediate precursor of phosphatidylserine synthesis.