To hydrolyze or not to hydrolyze: the dilemma of platelet-activating factor acetylhydrolase

To hydrolyze or not to hydrolyze: the dilemma of platelet-activating factor acetylhydrolase

Blog Article

Mounting ambiguity persists around the functional role of the plasma form of platelet-activating factor acetylhydrolase (PAF-AH).Because PAF-AH hydrolyzes PAF and related oxidized phospholipids, it is widely accepted as an anti-inflammatory enzyme.On the other hand, its actions can also generate lysophosphatidylcholine (lysoPC), a component of bioactive atherogenic oxidized LDL, thus allowing the enzyme to have proinflammatory capabilities.Presence of a canonical lysoPC receptor has been seriously questioned for a multitude of reasons.Animal models of inflammation show that elevating PAF-AH levels here is beneficial and not deleterious and overexpression of PAF receptor (PAF-R) also augments inflammatory responses.

Further, many Asian populations have a catalytically inert PAF-AH that appears to be a severity factor in keychron m4 a range of inflammatory disorders.Correlation found with elevated levels of PAF-AH and CVDs has led to the design of a specific PAF-AH inhibitor, darapladib.However, in a recently concluded phase III STABILITY clinical trial, use of darapladib did not yield promising results.Presence of structurally related multiple ligands for PAF-R with varied potency, existence of multi-molecular forms of PAF-AH, broad substrate specificity of the enzyme and continuous PAF production by the so called bi-cycle of PAF makes PAF more enigmatic.This review seeks to address the above concerns.