Target type: biologicalprocess
Any process that modulates the frequency, rate or extent of phosphatidylcholine biosynthetic process. [GOC:obol]
The regulation of phosphatidylcholine (PC) biosynthesis is a complex and tightly controlled process essential for maintaining cellular membrane integrity, signaling, and other vital functions. PC is the most abundant phospholipid in eukaryotic cell membranes, and its synthesis involves a coordinated interplay of enzymatic pathways and regulatory mechanisms.
**1. CDP-choline pathway:** This is the primary route for PC biosynthesis. It begins with the phosphorylation of choline by choline kinase (CK), forming phosphocholine. Phosphocholine then reacts with CTP (cytidine triphosphate) to produce CDP-choline. This step is catalyzed by CTP:phosphocholine cytidylyltransferase (CCT), a key regulatory enzyme. Finally, CDP-choline combines with diacylglycerol (DAG) via the action of CDP-choline:1,2-diacylglycerol cholinephosphotransferase (CPT), forming PC.
**2. Methylation pathway:** This pathway is less active but offers an alternative route to PC synthesis. It involves the methylation of phosphatidylethanolamine (PE) by sequential transfer of methyl groups from S-adenosylmethionine (SAM). This process is catalyzed by PE N-methyltransferases (PEMTs), which are also subject to regulation.
**3. Regulation at the level of enzyme activity:**
* **CCT:** CCT is the rate-limiting enzyme in the CDP-choline pathway. Its activity is regulated by various factors:
* **Substrate availability:** Choline and CTP levels can affect CCT activity.
* **Phosphatidylcholine levels:** Increased PC levels can feedback-inhibit CCT activity, preventing excessive PC synthesis.
* **Phosphorylation:** CCT can be phosphorylated by kinases, leading to its activation or inhibition depending on the specific kinase.
* **Transcriptional regulation:** Expression of CCT genes can be modulated by various transcription factors and signaling pathways.
* **PEMT:** PEMT activity is also regulated by various factors:
* **Substrate availability:** PE and SAM levels affect PEMT activity.
* **Transcriptional regulation:** PEMT gene expression can be influenced by various stimuli, including hormones and growth factors.
**4. Regulation at the level of membrane composition:**
* **Membrane lipid composition:** The abundance of specific phospholipids, including PC itself, can affect membrane fluidity and the activity of various membrane-associated enzymes. This regulation is based on the principles of lipid homeostasis.
* **Lipid trafficking:** The movement of phospholipids between different cellular compartments, such as the endoplasmic reticulum (ER) and the Golgi apparatus, contributes to the regulation of PC synthesis and membrane composition.
**5. Signaling pathways involved in PC biosynthesis:**
* **Insulin/IGF-1 signaling:** These pathways activate CCT and stimulate PC biosynthesis.
* **Growth factor signaling:** Growth factors, such as epidermal growth factor (EGF) and platelet-derived growth factor (PDGF), can also influence PC synthesis.
* **Steroid hormones:** Hormones like estrogen can regulate PC biosynthesis.
* **Stress responses:** Cellular stress, such as hypoxia or oxidative stress, can modulate PC synthesis to adapt to changing conditions.
**6. Cellular context:**
* **Cell type:** Different cell types exhibit distinct regulation of PC biosynthesis to fulfill their specific needs.
* **Developmental stage:** During development, PC synthesis undergoes significant changes to accommodate growth and differentiation.
**7. Disease implications:**
* **Disorders of PC biosynthesis:** Mutations in genes involved in PC synthesis can lead to severe neurological disorders, such as Niemann-Pick disease.
* **Cancer:** Altered PC biosynthesis is often observed in cancer cells, contributing to their uncontrolled growth and proliferation.
Overall, the regulation of phosphatidylcholine biosynthesis is a complex and tightly controlled process involving multiple enzymatic pathways, regulatory factors, and signaling pathways. Understanding this regulation is crucial for comprehending cellular function and disease pathogenesis.'
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Protein | Definition | Taxonomy |
---|---|---|
Fatty acid-binding protein, heart | A fatty acid-binding protein, heart that is encoded in the genome of human. [PRO:DNx, UniProtKB:P05413] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
truxillic acid | truxillic acid: RN given refers to cpd with unspecified isomeric designation; structure | ||
cocaine | cocaine : A tropane alkaloid obtained from leaves of the South American shrub Erythroxylon coca. Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. | benzoate ester; methyl ester; tertiary amino compound; tropane alkaloid | adrenergic uptake inhibitor; central nervous system stimulant; dopamine uptake inhibitor; environmental contaminant; local anaesthetic; mouse metabolite; plant metabolite; serotonin uptake inhibitor; sodium channel blocker; sympathomimetic agent; vasoconstrictor agent; xenobiotic |
linoleic acid | linoleic acid : An octadecadienoic acid in which the two double bonds are at positions 9 and 12 and have Z (cis) stereochemistry. Linoleic Acid: A doubly unsaturated fatty acid, occurring widely in plant glycosides. It is an essential fatty acid in mammalian nutrition and is used in the biosynthesis of prostaglandins and cell membranes. (From Stedman, 26th ed) | octadecadienoic acid; omega-6 fatty acid | algal metabolite; Daphnia galeata metabolite; plant metabolite |
HTS 01037 | ring assembly; thiophenes | ||
bms 309403 |