Oxygenation of Arachidonic Acid by Cytochromes P‐450

Oliw, Ernst H.; Ericsson, Johanna

doi:10.1002/9783527613625.ch6

Cited by 3 publications

(2 citation statements)

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“…An Me3Si ether group at C-20 is expected to give ions at mlz 103 [CH2=O+Si(CH3)3] (ucleavage, cf. [19,201) and 146 [CH2 =C+(OCH3)0Si(CH3)3] (McLafferty rearrangement of the 20-Me3Si ether group and the carboxyl group, cf. [20]).…”

Section: Compound Ifmentioning

confidence: 99%

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

Örning

1987

European Journal of Biochemistry

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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, (SS, 6R)-5,20-dihydroxy-6S-cysteinyl-7,9-trans-ll,l4-cis-icosatetraenoic acid (w-hydroxy-leukotriene E4) and (SS, 6R)-S-hydroxy-6S-cysteinyl-7,9-fruns-11,14-cis-icosatetraen-l,20-dioic acid (w-carboxy-leukotriene E,) suggested that leukotriene E4 was transformed by an o-hydroxylase and o-hydroxyleukotriene E dehydrogenase in sequence. N-Acetylleukotriene 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-o-hydroxy-leukotriene E4 and N-acetyl-w-carboxy-leukotriene E4. Other substrates were 11 -trans-leukotriene E4 and N-acetyl-1 1 -transleukotriene E4. In contrast, leukotrienes C4 and D4 were not converted into o-oxidized metabolites. The leukotriene E o-hydroxylase reaction required NADPH and molecular oxygen as cofactors, and was most rapidly catalyzed by liver microsomes. Liver cytosol, fortified with NAD' , converted o-hydroxyleukotriene E4 and N-acetyl-o-hydroxy-leukotriene E4 into o-carboxy metabolites. Microsomes contained at least 18 times less w-hydroxy-leukotriene E dehydrogenase activity than did cytosol. Liver microsomes supplemented with acetylcoenzyme A converted w-hydroxy and o-carboxy-leukotriene E4 into the corresponding N-acetyl derivatives. The novel enzyme, leukotriene E o-hydroxylase, which is described here is distinct from a previously described leukotriene B w-hydroxylase based on substrate competition and kinetic data.Previous investigations in our and other laboratories have shown that cysteine-containing leukotrienes [2] are extensively metabolized both in vitro and in vivo (reviewed in [3]). Following administration of tritium-labeled leukotriene C,, a biliary and two fecal metabolites in the rat (N-acetylleukotriene E4 and N-acetyl-11-trans-leukotriene E4 [4, 5]), a biliary metabolite in the guinea pig (leukotriene D4 [6]) and a biliary and urinary compound in pig and monkey and a urinary metabolite in man (leukotriene E4 [7 -91) were characterized. During the course of these and other (e.g. [lo, 111) investigations it was found that more polar metabolites were also formed from LTC. The relative amount of the latter compounds increased with time following LTC administration. Since a large Correspondence to L. Orning, Institutionen for Fysiologisk Kemi, Karolinska Institutet, S-104 01 Stockholm, SwedenAbbreviations. RP-HPLC, reverse-phase high-performance liquid chromatography; FAB-MS, fast-atom-bombardment mass spectrometry; GC-MS, gas-liquid chromatography/mass spectrometry; Me,Si, trimethylsilyl; LTB4, leukotriene B4; LTC4, leukotriene C4; LTD4, leukotriene D4; LTE4, leukotriene E4; N-Ac-LTE4, Nacetylleukotriene E4; 11 -trans-LTC4, 1 1-trans-leukotriene C4; 11-trans-LTE4, 1 1-trans-leukotriene E4; N-Ac-11 -trans-LTE4, N-acetyl-1 1-trans-leukotriene Ed; w-OH-LTE4, w-hydroxy-leukot...

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Section: Compound Ifmentioning

confidence: 99%

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

Örning

1987

European Journal of Biochemistry

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“…Ungesättigte Fettsäuren sind in Zellen stets in den Phospholipiden der Plasmamembran gespeichert, meist durch nooxygenasen katalysieren die Hydroxylierung von Arachidonsäure an den C- Atomen 5,7,8,9,10,11,12,13,15,16,18,19,20 sowie die Bildung von 5, 8,11,.Diese Primärprodukte können von der Zelle auf vielfältige Weise weiter verändert werden, sodass eine fast unüberschaubare Mannigfaltigkeit von potenziellen Wirkstoffen entsteht, deren Funktionen nur ansatzweise oder überhaupt noch nicht bekannt sind. Beschrieben wurden bisher vor allem Effekte auf die glatte Gefäßmuskulatur, durch die die Durchblutung der Niere und des Herzmuskels sowie der Blutdruck beeinflusst werden.…”

Section: Enzyme Der Oxylipin-und Eicosanoidbiosyntheseunclassified