Degradation Of Phospholipids

A variety of hydrolytic enzymes, the phospholipases, exists to remove selectively the different constituents of the phospholipid molecule: the acyl groups at positions 1 and 2 of phosphoglycerides, the phospho-base moiety or the base alone.

Phospholipases are classified according to the positions of their attack on the substrate molecule as illustrated in Fig. 7.8. Phospholipases of type A yield a monoacyl (lyso) phospholipid while phos-pholipases C and D yield a lipid (diacylglycerol and phosphatidic acid, respectively) and a water-soluble product. Phospholipase D can use an hydroxyl in an organic molecule instead of water and, thus, catalyse transphosphatidylation rather than hydrolysis. (This activity can result in the production of the artefact phosphatidylmethanol during

Table 7.2 Some effects of platelet activating factor (PAF) in different cells/tissues

Cell/tissue

Effect

Implications

Platelet

Degranulation, aggregation

Amine release, coronary thrombosis

Neutrophil

Chemotaxis, aggregation, superoxide generation

Antibacterial activity

Alveolar macrophage

Respiratory bursts, superoxide generation

Antibacterial activity

Liver

Inositide turnover, glycogenolysis stimulation

Overall control of activity

Exocrine secretory glands

Similar effects to acetylcholine

Overall control of activity

Leukaemic cells

Specific cytotoxicity towards the cells

Treatment?

Vascular permeability

Mimics acute and chronic inflammation

Pathogenesis of psoriasis?

Lungs

Increases airway and pulmonary oedema; decreases compliance

Asthma and other respiratory conditions

Fig. 7.8 Sites of action of phospholipases A, B, C and D.

methanol extraction of tissue extracts if the enzyme is not inactivated!) Phospholipases of type B differ from phospholipases A1 or A2 in that they can hydrolyse acyl groups at both positions, but they are relatively rare. There are also lysophos-pholipases and acyl hydrolases (which can act against acyl lipids in general) in some tissues.

All true phospholipases share the same general property of having relatively low activity against monomeric soluble phospholipids but become fully active against aggregated structures, such as phospholipid solutions above their critical micellar concentration or membrane phospholipids in bilayer or hexagonal structures. They play an obvious role as digestive enzymes whether it be in the digestive secretions of mammals (Section 5.1.1) or in bacterial secretions. In addition, some enzymes, such as phospholipase A2, play important roles in re-modelling the acyl composition of membrane lipids. Several types of phospholipase are needed for the production of lipid-derived signalling molecules (Sections 2.4, 7.9 and 7.11) and which are associated with cellular regulation.

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