Endogenously generated 5-hydroperoxyeicosatetraenoic acid is the preferred substrate for human leukocyte leukotriene A4 synthase activity.

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 X g supernatant was incubated with 100 microM octadeuterated arachidonic acid and exogenous 5-HPETE (0-80 microM), and the isotopic composition of LTA4 hydrolysis products was determined by gas chromatography-mass spectrometry. Even though 100 microM deuterated arachidonic acid results in 20-30 microM deuterated 5-HPETE, 80 microM 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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Puustinen T,Scheffer MM,Samuelsson B

doi

10.1016/0014-5793(87)80675-0

subject

Has Abstract

pub_date

1987-06-15 00:00:00

pages

265-8

issue

2

eissn

0014-5793

issn

1873-3468

pii

0014-5793(87)80675-0

journal_volume

217

pub_type

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