The Kennedy pathway is the principal de-novo route to the two most abundant membrane glycerophospholipids, phosphatidylcholine (PC) and phosphatidylethanolamine (PE). It runs as two parallel three-step branches that converge on a common diacylglycerol (DAG) acceptor. In the CDP-choline branch, choline kinase (CHKA/CHKB) phosphorylates choline to phosphocholine; the rate-limiting, membrane-regulated CTP:phosphocholine cytidylyltransferase (PCYT1A/PCYT1B) converts phosphocholine + CTP to CDP-choline; and a CDP-alcohol phosphotransferase (CHPT1, or the dual-specificity CEPT1) transfers phosphocholine from CDP-choline onto DAG to make PC + CMP. In the parallel CDP-ethanolamine branch, ethanolamine kinase (ETNK1/ETNK2) makes phosphoethanolamine, the rate-controlling CTP:phosphoethanolamine cytidylyltransferase (PCYT2) makes CDP-ethanolamine, and the ethanolaminephosphotransferases (the selenoprotein SELENOI/EPT1, or CEPT1) transfer phosphoethanolamine onto DAG to make PE + CMP. The two branches are linked by phosphatidylethanolamine N-methyltransferase (PEMT), an ER enzyme (liver-enriched) that performs three sequential SAM-dependent methylations of PE to PC — the only way to make PC without preformed choline, and a major consumer of methyl groups. The amphitropic cytidylyltransferase PCYT1A senses membrane PC content, making it the key regulatory node. Inherited defects span a striking phenotypic range: PCYT1A congenital lipodystrophy / spondylometaphyseal dysplasia with cone-rod dystrophy, CHKB megaconial congenital muscular dystrophy, and PCYT2 and SELENOI hereditary spastic paraplegia.
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No MODULE:kennedy_pathway_phospholipid_synthesis deep-research report alongside the module YAML.
✓ every leaf node grounds to a representative protein.
✓ every declared conforms_to bundle matches its template motif.
11 complete review(s) · 0 with deep research · 0 missing review · 11 reviewed but lacking deep research
| Gene | Review | Complete | Deep research |
|---|---|---|---|
| CEPT1 Q9Y6K0 | ✓ | ✓ | ✗ |
| CHKA P35790 | ✓ | ✓ | ✗ |
| CHKB Q9Y259 | ✓ | ✓ | ✗ |
| CHPT1 Q8WUD6 | ✓ | ✓ | ✗ |
| ETNK1 Q9HBU6 | ✓ | ✓ | ✗ |
| ETNK2 Q9NVF9 | ✓ | ✓ | ✗ |
| PCYT1A P49585 | ✓ | ✓ | ✗ |
| PCYT1B Q9Y5K3 | ✓ | ✓ | ✗ |
| PCYT2 Q99447 | ✓ | ✓ | ✗ |
| PEMT Q9UBM1 | ✓ | ✓ | ✗ |
| SELENOI Q9C0D9 | ✓ | ✓ | ✗ |
Kennedy pathway de-novo glycerophospholipid synthesis (GO:0006656 PC + GO:0006646 PE), grounded to eleven completed human gene reviews. CDP-CHOLINE branch -> PC: CHKA (P35790) + CHKB (Q9Y259) share PTHR22603, GO:0004103 (also ethanolamine kinase GO:0004305) -> PCYT1A (P49585) + PCYT1B (Q9Y5K3) share PTHR10739, GO:0004105 (rate-limiting, amphitropic; PCYT1A membrane-PC-sensing, shuttles nucleus<->ER) -> CHPT1 (Q8WUD6) + CEPT1 (Q9Y6K0) share PTHR10414, GO:0004142. CDP-ETHANOLAMINE branch -> PE: ETNK1 (Q9HBU6) + ETNK2 (Q9NVF9) share PTHR22603, GO:0004305 -> PCYT2 (Q99447 PTHR45780, GO:0004306, rate-controlling) -> SELENOI/EPT1 (Q9C0D9, a selenoprotein, + ether-PE) + CEPT1 share PTHR10414, GO:0004307. CROSSLINK: PEMT (Q9UBM1 PTHR15458, GO:0004608) methylates PE->PC 3x with SAM (only choline-independent PC route; NAFLD). CEPT1 is dual-specificity (appears in both phosphotransferase nodes). All 11 kinases/transferases require Mg2+/Mn2+; the DAG acceptor and CMP byproduct link to glycerolipid metabolism. GO term ids/labels verified against the local go.db. Disorders: PCYT1A lipodystrophy / SMD-CRD; CHKB megaconial muscular dystrophy; PCYT2 and SELENOI hereditary spastic paraplegia.
Phosphorylate choline to phosphocholine (also ethanolamine kinase activity).
Convert phosphocholine + CTP to CDP-choline (rate-limiting, membrane-regulated).
Transfer phosphocholine from CDP-choline to DAG, forming PC.
Phosphorylate ethanolamine to phosphoethanolamine.
Convert phosphoethanolamine + CTP to CDP-ethanolamine (rate-controlling).
Transfer phosphoethanolamine from CDP-ethanolamine to DAG, forming PE.
Methylate PE (3x SAM) to PC (choline-independent route).