CDP-choline pathway

Content sourced from Wikipedia, licensed under CC BY-SA 3.0.

The CDP-choline pathway is the main way mammalian cells make phosphatidylcholine (PC), a key phospholipid in membranes and signaling. It is one half of the Kennedy pathway; the other half makes phosphatidylethanolamine (PE).

How choline gets into cells
- Choline comes from the diet and enters cells mainly through several transporters:
- CHT: high-affinity, Na+-dependent and ATP-requiring.
- OCTs and OCTNs: lower-affinity, Na+-independent.
- CTL1: intermediate-affinity.
- In neurons, most choline becomes acetylcholine; in most other cells, choline enters the CDP-choline pathway.

Step 1: how choline is activated
- Choline kinase (CK) adds a phosphate to choline to form phosphocholine. CK can also phosphorylate ethanolamine, linking to another pathway.

Step 2: forming CDP-choline (rate-limiting)
- CTP:phosphocholine cytidylyltransferase (CCT) converts phosphocholine to CDP-choline. This is the rate-limiting step.
- There are two CCT forms, CCTα and CCTβ. CCTα has a nuclear localization signal and shuttles between the nucleus and cytoplasm; CCTβ is mainly cytosolic.

Step 3: making phosphatidylcholine
- Choline/ethanolamine phosphotransferase (CEPT) or choline phosphotransferase (CPT) attach the choline headgroup to diacylglycerol (DAG) to form PC.
- CPT mainly works in the Golgi; CEPT works in the endoplasmic reticulum and can use both CDP-choline and CDP-ethanolamine. CEPT generally handles most PC synthesis, while CPT helps with DAG regulation in the Golgi.

Regulation and metabolism
- The finished PC can be broken down by phospholipases into other lipids and signaling molecules.
- CK and CCT regulation matters: CKα and CKβ are two CK forms with tissue differences (CKα is important in testis and liver; CKβ in liver and heart; removing CKα is embryonically lethal).
- CCTα and CCTβ differ in localization and activation. CCTα activity increases when membranes need PC, and it binds membranes (amphitropic) to become active.
- Under normal conditions, CPT/CEPT are not the rate-limiting step, but they can become limiting if DAG is restricted.

Dietary need
- Mammalian cells cannot make enough choline on their own, so dietary choline is essential to supply this pathway.