Intracellular Erythrocyte Platelet-activating Factor Acetylhydrolase I Inactivates Aspirin in Blood

Abstract

Background: Aspirin circulates transiently in blood, but the identity of the enzyme(s) that hydrolyzes its acetyl residue remains unknown. Results: Purification, mass spectrometry, and overexpression identified erythrocyte type I PAF acetylhydrolase as aspirin hydrolase. Conclusion: Aspirin is primarily hydrolyzed within erythrocytes by PAF acetylhydrolase. Significance: PAF acetylhydrolase and aspirin hydrolysis varies among individuals to modulate the effectiveness of aspirin.

Aspirin Hydrolysis in Plasma Is a Variable Function of Butyrylcholinesterase and Platelet-activating Factor Acetylhydrolase 1b2 (PAFAH1b2)

“…Type I PAFAH is an ␣1/␣2 heterodimer composed of independent genes (PAFAH1b2 and PAFAH1b3) that are independently regulated and have independent roles (46 -48). We previously identified the ␣1/␣2 heterodimer as the aspirin hydrolytic enzyme of erythrocytes (20), so the novel plasma ␣2 enzyme shows that this extracellular enzyme is not derived from lysed erythrocytes.…”

“…Purification of soluble fraction 1 and mass spectrometry of candidate proteins as described (20) revealed the presence of PAFAH1b2 in plasma (data not shown.) Type I PAFAH hydrolyzes acetylated phospholipids but additionally accepts aspirin as a substrate (20).…”

“…Type I PAFAH hydrolyzes acetylated phospholipids but additionally accepts aspirin as a substrate (20). This intracellular enzyme is a trimer con-FIGURE 1.…”

“…Aspirin is hydrolyzed in blood within erythrocytes (19) by a heterodimer of PAFAH1b2 and PAFHA1b3 (20) and also in plasma. The rate of aspirin hydrolysis by erythrocytes varies severalfold (20), with a larger variation in the rate of plasma hydrolysis (see below), so the relative contribution of the two compartments varies but is approximately similar.…”

“…The rate of aspirin hydrolysis by erythrocytes varies severalfold (20), with a larger variation in the rate of plasma hydrolysis (see below), so the relative contribution of the two compartments varies but is approximately similar. The identity of the enzyme in plasma that hydrolyzes aspirin remains unknown.…”