Phospholipid Synthesis (Kennedy / CDP pathways)

1. 1

   Choline + ATP -> phosphocholine + ADP

   Choline kinase 2.7.1.32 ST-0305 Irreversible/directional ATP Mg2+
   In Choline ATP

   Out Phosphocholine ADP
   › Notes

   Dietary/salvaged choline is trapped by phosphorylation.

2. 2

   Phosphocholine + CTP -> CDP-choline + PPi

   CTP:phosphocholine cytidylyltransferase (CCT) 2.7.7.15 ST-0306 Irreversible rate-limiting CTP
   In Phosphocholine CTP

   Out CDP-choline PPi
   › Notes

   Rate-limiting step of phosphatidylcholine synthesis; regulated by reversible membrane association of CCT.

3. 3

   CDP-choline + 1,2-diacylglycerol -> phosphatidylcholine + CMP

   CDP-choline:DAG cholinephosphotransferase 2.7.8.2 ST-0307 Irreversible/directional
   In CDP-choline Diacylglycerol

   Out Phosphatidylcholine CMP
   › Notes

   Principal route to phosphatidylcholine, the main membrane and surfactant phospholipid (DPPC).

4. 4

   Phosphatidic acid + CTP -> CDP-diacylglycerol + PPi

   CDP-DAG synthase (CDS1/2) 2.7.7.41 ST-0308 Irreversible/directional CTP
   In Phosphatidic acid CTP

   Out CDP-diacylglycerol PPi
   › Notes

   Alternative activated intermediate used for the acidic phospholipids.

5. 5

   CDP-diacylglycerol + inositol -> phosphatidylinositol + CMP

   Phosphatidylinositol synthase (CDIPT) 2.7.8.11 ST-0309 Irreversible/directional
   In CDP-diacylglycerol Inositol

   Out Phosphatidylinositol CMP
   › Notes

   PI is the precursor of PIP2, the substrate for phospholipase C signalling.

6. 6

   Phosphatidylethanolamine + 3 SAM -> phosphatidylcholine + 3 SAH

   Phosphatidylethanolamine N-methyltransferase (PEMT) 2.1.1.17 ST-0310 Irreversible/directional SAM
   In Phosphatidylethanolamine S-adenosylmethionine (SAM)

   Out Phosphatidylcholine S-adenosylhomocysteine
   › Notes

   Hepatic salvage route to PC; a major consumer of SAM and a link to the methionine cycle.

Showing all 6 steps.