The hydrolytic reactivity of homoprostacyclin: implications for the physiological control of bleeding

Abstract

Rates of hydrolysis of the vinyl ether group of homoprostacyclin (2), which differs from prostacyclin only in that it has four instead of three carbon atoms in the chain joining this group to a carboxy function, were measured in H₂O solution over the pH range 1–9 and in D₂O solution in D₂PO₄^––DPO₄^2– buffers. The rate profile so obtained shows that homoprostacyclin is eight times more reactive in its carboxylate than in its carboxylic acid form, and an isotope effect on the accelerated reaction indicates that this rate increase is the result of intramolecular catalysis by the carboxylic acid group. This eight-fold acceleration is significantly less than the 100-fold increase produced by intramolecular catalysis in the case of prostacyclin itself, and that suggests that natural evolution has given prostacyclin the correct lifetime it needs to be effective in the physiological mechanism for the control of bleeding by adjusting the length of the carbon chain joining its vinyl ether and carboxy groups.