Beyond COX-1: the effects of aspirin on platelet biology and potential mechanisms of chemoprevention

Figures

• 

  Fig. 1. The Chemistry of Aspirin Under Basic Conditions. Deprotonation of the carboxylic acid results in the formation of the aspirin anion which abstracts a proton from water to generate a nucleophilic hydroxide anion. The negatively charged hydroxide attacks the carbonyl carbon of the acetate group resulting in hydrolysis of aspirin into salicylate and acetate (general base catalysis) [15, 16]. Recent work also suggests that a mixed anhydride can be formed under basic conditions through a hemiorthoester anion intermediate [18] although the contribution of this intermediate to the mechanism of hydrolysis is unknown

• 

  Fig. 2. Reactivity of aspirin in different biological environments of proteins

• 

  Fig. 3. Platelet Activation. Platelet activation is initiated by multiple stimuli including thrombin, ADP, and fibrinogen. This results in the initiation of prostaglandin synthesis by COX-1 which is directly inhibited by aspirin. Aspirin can also modulate the clotting response by acetylating other serum proteins, most notably fibrinogen