Fospholipases

Fospholipases, a term rarely used in modern literature, refer to enzymes that hydrolyze phospholipids, the major components of cell membranes. In practice, the enzymes are described as phospholipases. They are widespread across life and participate in membrane remodeling, signaling, digestion, and host defense.

Phospholipases are traditionally grouped by the bond they cleave within the phospholipid molecule. Phospholipase A1 (PLA1) hydrolyzes the sn-1 acyl bond, releasing a fatty acid and a lysophospholipid. Phospholipase A2 (PLA2) cleaves the sn-2 acyl bond, releasing a free fatty acid—often arachidonic acid—and a lysophospholipid. Phospholipase C (PLC) splits the bond before the phosphate, producing diacylglycerol and a phosphorylated head group. Phospholipase D (PLD) cleaves the head group from the phosphate, yielding phosphatidic acid and the head moiety. Additional variants, such as phospholipase B, exhibit dual A1/A2 activities. Within these broad classes there are secreted and cytosolic forms (e.g., secreted PLA2, cytosolic PLA2) with distinct regulatory features and tissue distributions.

Mechanistically, phospholipase activity is regulated by cellular context. Many secreted PLA2 enzymes require calcium ions; others are controlled by phosphorylation, substrate availability, or membrane association. The products of phospholipase reactions—free fatty acids, lysophospholipids, diacylglycerol, phosphatidic acid, and phosphorylated head groups—serve as signaling molecules or precursors for further lipid mediators. For example, PLA2 products can feed into inflammatory pathways, while PLC products participate in diverse intracellular signaling cascades.

Biological and medical relevance includes roles in digestion, membrane dynamics, inflammation, and immunity. Dysregulation is associated with diseases such as arthritis, cardiovascular disorders, and neurodegeneration. Some phospholipases are also employed as toxins by venomous animals.