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Endogenously generated 5‐hydroperoxyeicosatetraenoic acid is the preferred substrate for human leukocyte leukotriene A 4 synthase activity
Author(s) -
Puustinen Tapio,
Scheffer Mark M.,
Samuelsson Bengt
Publication year - 1987
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(87)80675-0
Subject(s) - atp synthase , substrate (aquarium) , chemistry , biochemistry , enzyme , leukotriene , stereochemistry , biology , immunology , ecology , asthma
A single protein from human leukocytes possesses both 5‐lipoxygenase and leukotriene A 4 (LTA 4 ) synthase activities. It has been reported that LTA 4 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 LTA 4 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 LTA 4 by only approx. 20%. The present study would thus indicate that the arachidonic acid moiety is preferentially converted to LTA 4 in a concerted reaction without dissociation of a 5‐HPETE intermediate.