Endogenously generated 5‐hydroperoxyeicosatetraenoic acid is the preferred substrate for human leukocyte leukotriene A4 synthase activity
- 15 June 1987
- journal article
- research article
- Published by Wiley in FEBS Letters
- Vol. 217 (2) , 265-268
- https://doi.org/10.1016/0014-5793(87)80675-0
Abstract
A single protein from human leukocytes possesses both 5‐lipoxygenase and leukotriene A4 (LTA4) synthase activities. It has been reported that LTA4 production is more efficient when the enzyme utilizes arachidonic acid, than when 5‐HPETE is exogenously supplied as substrate. In the present study, human leukocyte homogenate 100 000 × g supernatant was incubated with 100 μM octadeuterated arachidonic acid and exogenous 5‐HPETE (0–80 μM), and the isotopic composition of LTA4 hydrolysis products was determined by gas chromatography‐mass spectrometry. Even though 100 μM deuterated arachidonic acid results in 20–30 μM deuterated 5‐HPETE, 80 μM exogenous 5‐HPETE in the incubation could reduce the amount of deuterated LTA4 by only approx. 20%. The present study would thus indicate that the arachidonic acid moiety is preferentially converted to LTA4 in a concerted reaction without dissociation of a 5‐HPETE intermediate.Keywords
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