DOI: 10.1111/j.1432-1033.1987.tb13669.x. ω‐Oxidation of cysteine‐containing leukotrienes by rat‐liver microsomes

ω‐Oxidation of cysteine‐containing leukotrienes by rat‐liver microsomes

10.1111/j.1432-1033.1987.tb13669.x

Crossref journal-article

Wiley

European Journal of Biochemistry (311)

Abstract

Leukotriene E4 was metabolized to two polar products by rat liver microsomes. These products were characterized by physico‐chemical and chemical techniques. The chemical structures, (5S, 6R)‐5,20‐dihydroxy‐6S‐cysteinyl‐7,9‐trans‐11,14‐cis‐icosatetraenoic acid (ω‐hydroxy‐leukotriene E4) and (5S, 6R)‐5‐hydroxy‐6S‐cysteinyl‐7,9‐trans‐11,14‐cis‐icosatetraen‐1,20‐dioic acid (ω‐carboxy‐leukotriene E4) suggested that leukotriene E4 was transformed by an ω‐hydroxylase and ω‐hydroxyleukotriene E dehydrogenase in sequence. N‐Acetyl‐leukotriene E4 was also transformed by these enzymes, but at a rate six times lower than leukotriene E4. The products formed from N‐acetylleukotriene E4 were characterized as being N‐acetyl‐ω‐hydroxy‐leukotriene E4 and N‐acetyl‐ω‐carboxy‐leukotriene E4. Other substrates were 11‐trans‐leukotriene E4 and N‐acetyl‐11‐trans‐leukotriene E4. In contrast, leukotrienes C4 and D4 were not converted into ω‐oxidized metabolites. The leukotriene E ω‐hydroxylase reaction required NADPH and molecular oxygen as cofactors, and was most rapidly catalyzed by liver microsomes. Liver cytosol, fortified with NAD+, converted ω‐hydroxyleukotriene E4 and N‐acetyl‐ω‐hydroxy‐leukotriene E4 into ω‐carboxy metabolites. Microsomes contained at least 18 times less ω‐hydroxy‐leukotriene E dehydrogenase activity than did cytosol. Liver microsomes supplemented with acetyl‐coenzyme A converted ω‐hydroxy and ω‐carboxy‐leukotriene E4 into the corresponding N‐acetyl derivatives. The novel enzyme, leukotriene E ω‐hydroxylase, which is described here is distinct from a previously described leukotriene B ω‐hydroxylase based on substrate competition and kinetic data.

Bibliography

ÃRNING, L. (1987). ÏâOxidation of cysteineâcontaining leukotrienes by ratâliver microsomes. European Journal of Biochemistry, 170(1â2), 77â85. Portico.

Authors 1

Lars ÖRNING (first)

References 31 Referenced 44

10.1016/0006-291X(87)90670-X
10.1146/annurev.bi.52.070183.002035
10.1007/BF00225922 / Mol. Cell Biochem. by Hammarström S. (1985)
10.1016/S0021-9258(17)36160-4 / J. Biol. Chem. by Örning L. (1986)
10.1016/0090-6980(86)90050-X
Keppler A. Örning L. Bernström K.&Hammarström S.(1987)Proc. Natl Acad. Sci. USA in the press.
10.1016/0090-6980(87)90037-2
10.1016/S0021-9258(18)66757-2
10.1016/0006-291X(85)90404-8
10.1016/S0021-9258(19)68800-9
10.1016/S0021-9258(19)68396-1
10.1016/S0022-2275(20)41684-0
{'key': 'e_1_2_3_14_2', 'first-page': '227', 'volume': '29', 'author': 'Kurtz W.', 'year': '1982', 'journal-title': 'Hepato-gastroenterology'} / Hepato-gastroenterology by Kurtz W. (1982)
10.1073/pnas.76.9.4275
10.1016/S0076-6879(85)11006-2
10.1016/0090-6980(82)90046-6
10.1016/0014-5793(81)80110-X / FEBS Lett. by Lindnren. J.‐Å. (1981)
10.1016/S0021-9258(17)43263-7
10.1016/S0021-9258(18)67642-2
10.1002/oms.1210010413
10.1016/0006-291X(80)90537-9
10.1016/S0021-9258(20)65143-2
10.1016/0003-9861(86)90617-X
10.1007/BF02116235
10.1016/S0167-7306(08)60533-5
10.1016/S0021-9258(17)43408-9 / J. Biol. Chem. by Wong P. (1984)
10.1016/0014-5793(81)80676-X
10.1016/S0021-9258(19)57231-3
10.1073/pnas.82.8.2292
10.1172/JCI112077
10.1016/S0021-9258(19)75676-2

Dates

Type	When
Created	20 years, 6 months ago (March 3, 2005, 8:52 p.m.)
Deposited	2 years ago (Aug. 30, 2023, 3:54 p.m.)
Indexed	16 hours, 2 minutes ago (Sept. 4, 2025, 9:53 a.m.)
Issued	37 years, 9 months ago (Dec. 1, 1987)
Published	37 years, 9 months ago (Dec. 1, 1987)
Published Online	20 years, 6 months ago (March 3, 2005)
Published Print	37 years, 9 months ago (Dec. 1, 1987)

Funders 0

None

BibTeX

@article{_RNING_1987, title={ω‐Oxidation of cysteine‐containing leukotrienes by rat‐liver microsomes: Isolation and characterization of ω‐hydroxy and ω‐carboxy metabolites of leukotriene E4 and N‐acetylleukotriene E4}, volume={170}, ISSN={1432-1033}, url={http://dx.doi.org/10.1111/j.1432-1033.1987.tb13669.x}, DOI={10.1111/j.1432-1033.1987.tb13669.x}, number={1–2}, journal={European Journal of Biochemistry}, publisher={Wiley}, author={ÖRNING, Lars}, year={1987}, month=dec, pages={77–85} }

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