sphinganine-1-phosphate biosynthetic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the formation of sphinganine-1-phosphate, the phosphorylated derivative of D-erythro-2-amino-1,3-octadecanediol. [GOC:ai]

Sphinganine-1-phosphate (S1P) biosynthesis is a crucial process in cellular signaling and membrane structure. It involves the conversion of dihydrosphingosine (DHS) to S1P, a bioactive lipid mediator with diverse functions. The process is catalyzed by a series of enzymes:
* **Sphingosine kinase 1 (SphK1) and sphingosine kinase 2 (SphK2):** These enzymes phosphorylate sphingosine to produce S1P. SphK1 is primarily localized in the cytoplasm, while SphK2 is predominantly found in the nucleus and Golgi apparatus.
* **Ceramide kinase (CerK):** CerK can also contribute to S1P synthesis by directly phosphorylating ceramide, although this pathway is less significant compared to SphK1/2.
**The biosynthesis of S1P involves the following steps:**
1. **De novo synthesis:** Sphingosine is initially generated through the de novo synthesis pathway, which starts with palmitoyl-CoA and serine as substrates.
2. **Sphingosine phosphorylation:** SphK1/2 catalyze the transfer of a phosphate group from ATP to the 1-hydroxyl group of sphingosine, generating S1P. This phosphorylation step is reversible, and S1P can be dephosphorylated back to sphingosine by S1P phosphatases.
3. **S1P transport:** S1P is transported across cellular membranes by specific S1P transporters, such as Spns2.
**S1P signaling:**
S1P exerts its biological functions by binding to and activating five specific G protein-coupled receptors (S1PRs) on the cell surface. These receptors are coupled to various downstream signaling pathways, leading to diverse cellular responses, including:
* **Cell survival and proliferation:** S1P promotes cell survival and proliferation in various cell types, including endothelial cells, immune cells, and neurons.
* **Cell migration and angiogenesis:** S1P plays a critical role in cell migration and angiogenesis by promoting the formation of new blood vessels.
* **Immune regulation:** S1P modulates immune responses by controlling lymphocyte trafficking and regulating immune cell function.
* **Nervous system development:** S1P is essential for nervous system development and function, contributing to neuronal survival, myelination, and axon guidance.
**Overall, S1P biosynthesis is a complex and tightly regulated process that plays a vital role in various cellular and physiological functions. Dysregulation of S1P biosynthesis and signaling has been implicated in various diseases, including cancer, cardiovascular disease, and autoimmune disorders.'
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Proteins (1)

Compounds (9)