PAL

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PAL-I

Phospholipase A2 (PLA2) is an enzyme that hydrolyzes the sn-2 acyl bond of phospholipids, releasing arachidonic acid and lysophospholipids. The action of PLA2 is a key step in the phospholipid metabolism and the biosynthesis of eicosanoids, including prostaglandins, thromboxanes, and leukotrienes, which play critical roles in inflammation and other physiological processes.

Function[edit | edit source]

PLA2 enzymes are involved in diverse biological processes, including membrane remodeling, lipid signaling, and the generation of second messengers. They are crucial for the production of eicosanoids, which are potent mediators of inflammation and have roles in immune response, pain, fever, and blood clotting. PLA2 enzymes are also implicated in the pathogenesis of various diseases, such as arthritis, asthma, and neurodegenerative diseases.

Classification[edit | edit source]

PLA2 enzymes are classified into several groups based on their structure, catalytic mechanism, and cellular localization. The main classes include:

- Secretory PLA2 (sPLA2): These are low molecular weight enzymes secreted by cells and found in various body fluids. They require calcium for activity and are involved in the initial steps of inflammation. - Cytoplasmic PLA2 (cPLA2): These enzymes are found in the cytosol and play a key role in the release of arachidonic acid from membrane phospholipids, particularly in response to cellular signals. - Calcium-independent PLA2 (iPLA2): These enzymes do not require calcium for their activity and are involved in the maintenance of cellular phospholipid homeostasis and the repair of membrane phospholipids.

Pathological Roles[edit | edit source]

Abnormal PLA2 activity has been associated with various diseases. Overexpression or heightened activity of PLA2 can lead to excessive production of eicosanoids, contributing to inflammation and disease progression in conditions such as rheumatoid arthritis, asthma, and atherosclerosis. Inhibitors of PLA2 have been researched for their potential therapeutic effects in treating these diseases.

Therapeutic Applications[edit | edit source]

Given its central role in inflammation and disease, PLA2 has been a target for drug development. Inhibitors of PLA2 are being explored as potential treatments for inflammatory diseases, with the aim of reducing the production of pro-inflammatory eicosanoids. However, the development of PLA2 inhibitors as therapeutic agents requires careful consideration of their specificity and potential side effects, given the enzyme's involvement in critical physiological processes.

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Contributors: Prab R. Tumpati, MD