Protein regulators of eicosanoid synthesis: role in inflammation

Area of Science:

• Biochemistry
• Immunology
• Pathophysiology

Background:

• Inflammation is initiated by diverse agents activating mediators.
• Early inflammation involves excessive cytokine and mediator release.
• Lipid synthesis pathways are critical in inflammatory pathogenesis and organ dysfunction.

Purpose of the Study:

• Review the function of key enzymes in eicosanoid synthesis.
• Discuss the regulation of these enzymes and their role in inflammatory disorders.
• Examine the properties, function, and regulation of protein activators PLAP and FLAP.

Main Methods:

• Review of literature on enzymes and protein activators involved in inflammation.
• Analysis of the roles of phospholipase A(2) (PLA(2)), cyclooxygenase (COX), and lipoxygenase (LO) enzymes.
• Discussion of the function of phospholipase-A(2)-activating protein (PLAP) and 5-lipoxygenase-activating protein (FLAP).

Main Results:

• Arachidonic acid (AA) is released by PLA(2) and metabolized by COX and LO to prostaglandins (PGs) and leukotrietes (LTs).
• Disordered activation of PLA(2), LO, and COX is implicated in numerous inflammatory diseases.
• The inducible COX-2 enzyme is upregulated during inflammation.

Conclusions:

• Enzymes like PLA(2), COX, and LO, and their activators PLAP and FLAP, are central to eicosanoid synthesis and inflammatory processes.
• Understanding these pathways is crucial for addressing inflammatory disorders.
• Dysregulation of these lipid mediators contributes significantly to disease pathogenesis.