regulation of prostaglandin catabolic process

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of prostaglandin catabolic process. [GO_REF:0000058, GOC:TermGenie, PMID:12432938]

Prostaglandins (PGs) are lipid mediators derived from arachidonic acid that play crucial roles in inflammation, pain, fever, and other physiological processes. Regulation of prostaglandin catabolic process ensures the appropriate duration and intensity of PG signaling, preventing excessive or prolonged inflammatory responses. This regulation is achieved through a complex interplay of enzymatic pathways, including:

1. **Prostaglandin Dehydrogenase (PGDH):** This enzyme, primarily expressed in the liver and kidney, catalyzes the initial step in PG catabolism, converting PGE2 to 15-keto-PGE2, a biologically inactive metabolite. This reaction is NAD+-dependent and involves oxidation of the 15-hydroxyl group of PGE2.

2. **15-Hydroxyprostaglandin Dehydrogenase (15-PGDH):** This enzyme catalyzes the NAD+-dependent oxidation of the 15-hydroxyl group of PGE2, converting it to 15-keto-PGE2. 15-PGDH is expressed in various tissues and contributes significantly to PG inactivation.

3. **Prostaglandin E Synthase (PGES):** This enzyme family, including microsomal PGES-1 and cytosolic PGES-2, is responsible for the conversion of PGH2 to PGE2, a key pro-inflammatory PG. Their activity is tightly regulated, ensuring controlled PGE2 production.

4. **Prostaglandin F Synthase (PGFS):** This enzyme converts PGH2 to PGF2α, another important pro-inflammatory PG. Its activity is also tightly regulated, similar to PGES.

5. **Prostaglandin I Synthase (PGIS):** This enzyme, also known as prostacyclin synthase, converts PGH2 to prostacyclin (PGI2), a potent vasodilator and anti-platelet agent. Its activity is regulated by various factors, including shear stress and nitric oxide.

6. **Prostaglandin D Synthase (PGDS):** This enzyme converts PGH2 to PGD2, a PG involved in allergic reactions and inflammation. Its activity is regulated by various factors, including cytokines and growth factors.

The regulation of prostaglandin catabolic process involves both transcriptional and post-translational mechanisms. For instance, PGDH expression can be induced by glucocorticoids, anti-inflammatory drugs that suppress inflammation by reducing PG production. Post-translational modifications, such as phosphorylation and ubiquitination, can also influence the activity of enzymes involved in PG catabolism.

In addition to enzymatic regulation, other factors contribute to controlling the duration and intensity of PG signaling. These include:

* **Cellular uptake and transport:** PGs can be taken up by cells and transported to different compartments, influencing their bioavailability and degradation.
* **Binding to receptors:** PGs exert their effects by binding to specific G protein-coupled receptors (GPCRs), activating intracellular signaling pathways. Receptor expression and availability can influence the response to PGs.
* **Inactivation by other mechanisms:** Some PGs can be inactivated by other mechanisms, such as conjugation with glutathione or oxidation by reactive oxygen species.

Dysregulation of prostaglandin catabolic process can contribute to various pathological conditions, including chronic inflammation, cancer, and cardiovascular disease. Understanding the intricate mechanisms underlying this process is crucial for developing novel therapeutic strategies targeting PG signaling.'
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Proteins (1)

Compounds (5)