Biochemistry of prostaglandins Flashcards
Biosynthesis of eicosanoids
Prostaglandins are found in most tissues and organs. They are produced by almost all ——— cells. They are ——- and ——- lipid mediators that act upon ———-, ————, ——— and ——— cells. They are synthesized in the cell from the fatty acid ———- acid.[2]
Prostaglandins are found in most tissues and organs. They are produced by almost all nucleated cells. They are autocrine and paracrine lipid mediators that act upon platelets, endothelium, uterine and mast cells. They are synthesized in the cell from the fatty acid arachidonic acid.[2]
Arachidonic acid is created from ——— via ————, then brought to either the ———- pathway or the ———- pathway.
Arachidonic acid is created from diacylglycerol via phospholipase-A2, then brought to either the cyclooxygenase pathway or the lipoxygenase pathway.
The cyclooxygenase enzyme pathway:
produces ———, ————- and prostaglandin —, —and —-.
produces thromboxane, prostacyclin and prostaglandin D, E and F.
The lipoxygenase enzyme pathway:
active in ——- and in ——- and synthesizes ———
active in leukocytes and in macrophages and synthesizes leukotrienes
Uptake and release of prostaglandins from the cell
Prostaglandins were originally believed to leave the cells via passive diffusion because of their high lipophilicity. The discovery of the prostaglandin transporter (PGT, SLCO2A1), which mediates the cellular uptake of prostaglandin, demonstrated that diffusion alone cannot explain the penetration of prostaglandin through the cellular membrane. The release of prostaglandin has now also been shown to be mediated by a specific transporter, namely the multidrug resistance protein 4 (MRP4, ABCC4), a member of the ATP-binding cassette transporter superfamily. Whether MRP4 is the only transporter releasing prostaglandins from the cells is still unclear
How are prostaglandins produced?
Prostaglandins are produced following the sequential oxygenation of arachidonic acid, DGLA or EPA by cyclooxygenases (COX-1 and COX-2) and terminal prostaglandin synthases
What are COX-1 and COX-2 enzymes responsible for?
COX-1 is responsible for the baseline levels of prostaglan,dins.
COX-2 produces prostaglandins through stimulation
Where are both COX-1 and COX-2 enzymes located?
Blood vessels, stomach, and kidneys
What is the most abundant prostaglandin?
Prostaglandin E2
How is Prostaglandin E2 generated?
generated from the action of prostaglandin E synthases on prostaglandin H2 (prostaglandin H2, PGH2). Several prostaglandin E synthases have been identified. To date, microsomal (named as misoprostol) prostaglandin E synthase-1 emerges as a key enzyme in the formation of PGE2.
