Inhibition of prostaglandin synthase activity of sheep seminal vesicular gland by human serum haptoglobin

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Abstract
Serum haptoglobin was added to the reaction mixture of prostaglandin synthase (EC 1.14.99.1) and its inhibitory effect was studied. [1-14C]Arachidonic acid was used as substrate and the enzyme activity was estimated by monitoring the radioactivity of the products after thin layer chromatography. With or without addition of hemoglobin to the reaction mixture, both the purified haptoglobin 1-1 and 2-2 showed inhibitory activity. In the presence of 5 μM hematin, however, inhibitory activity of haptoglobin was not observed. Inhibition of prostaglandin synthesis in the system depended on the molar ratio of haptoglobin to hemoglobin in the reaction mixture. These results demonstrate that haptoglobin inhibits prostaglandin synthase by restricting available heme group for the enzyme activity through complexing with hemoglobin. However, haptoglobin did not inhibit completely the stimulatory effect of free hemoglobin. Relevant significance of this effect was discussed.