scholarly journals Cytochrome P450/NADPH-dependent biosynthesis of 5,6-trans-epoxyeicosatrienoic acid from 5,6-trans-arachidonic acid

2005 ◽  
Vol 390 (3) ◽  
pp. 719-727 ◽  
Author(s):  
Uzzal Roy ◽  
Robert Joshua ◽  
Russell L. Stark ◽  
Michael Balazy
Keyword(s):  
Arachidonic Acid ◽  
Cytochrome P450 ◽  
Fatty Acid ◽  
Trans Fatty Acid ◽  
Oxidative Metabolism ◽  
Liver Microsomes ◽  
Complex Mixture ◽  
Metabolic Activation ◽  
Lipid Mediator ◽  
Epoxyeicosatrienoic Acid

5,6-trans-AA (5,6-TAA, where TAA stands for trans-arachidonic acid) is a recently identified trans fatty acid that originates from the cis–trans isomerization of AA initiated by the NO2 radical. This trans fatty acid has been detected in blood circulation and we suggested that it functions as a lipid mediator of the toxic effects of NO2. To understand its role as a lipid mediator, we studied the metabolism of 5,6-TAA by liver microsomes stimulated with NADPH. Profiling of metabolites by liquid chromatography/MS revealed a complex mixture of oxidized products among which were four epoxides, their respective hydrolysis products (dihydroxyeicosatrienoic acids), and several HETEs (hydroxyeicosatetraenoic acids) resulting from allylic, bis-allylic and (ω−1)/(ω−2) hydroxylations. We found that the C5–C6 trans bond competed with the three cis bonds for oxidative metabolism mediated by CYP (cytochrome P450) epoxygenase and hydroxylase. This was evidenced by the detection of 5,6-trans-EET (where EET stands for epoxyeicosatrienoic acid), 5,6-erythro-dihydroxyeicosatrienoic acid and an isomer of 5-HETE. A standard of 5,6-trans-EET obtained by iodolactonization of 5,6-TAA was used for the unequivocal identification of the unique microsomal epoxide in which the oxirane ring was of trans configuration. Additional lipid products originated from the metabolism involving the cis bonds and thus these metabolites had the trans C5–C6 bond. The 5,6-trans-isomers of 18- and 19-HETE were likely to be products of the CYP2E1, because a neutralizing antibody partially inhibited their formation without having an effect on the formation of the epoxides. Our study revealed a novel pathway of microsomal oxidative metabolism of a trans fatty acid in which both cis and trans bonds participated. Of particular significance is the detection of the trans-epoxide of AA, which may be involved in the metabolic activation of such trans fatty acids and probably contribute to their biological activity. Unlike its cis-isomer, 5,6-trans-EET was significantly more stable and resisted microsomal hydrolysis and conjugation with glutathione catalysed by hepatic glutathione S-transferase.

scholarly journals Eicosanoid turnover in GtoPdb v.2021.3

2021 ◽  
Vol 2021 (3) ◽  
Author(s):  
Angelo A. Izzo ◽  
Jane A. Mitchell
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Arachidonic Acid ◽  
Cytochrome P450 ◽  
Free Radicals ◽  
Phospholipase A2 ◽  
Oxidative Metabolism ◽  
Molecular Targets ◽  
Structural Analogues ◽  
Biomarkers Of Oxidative Stress

Eicosanoids are 20-carbon fatty acids, where the usual focus is the polyunsaturated analogue arachidonic acid and its metabolites. Arachidonic acid is thought primarily to derive from phospholipase A2 action on membrane phosphatidylcholine, and may be re-cycled to form phospholipid through conjugation with coenzyme A and subsequently glycerol derivatives. Oxidative metabolism of arachidonic acid is conducted through three major enzymatic routes: cyclooxygenases; lipoxygenases and cytochrome P450-like epoxygenases, particularly CYP2J2. Isoprostanes are structural analogues of the prostanoids (hence the nomenclature D-, E-, F-isoprostanes and isothromboxanes), which are produced in the presence of elevated free radicals in a non-enzymatic manner, leading to suggestions for their use as biomarkers of oxidative stress. Molecular targets for their action have yet to be defined.

Oxidative metabolism of 5-methoxy-N,N-diisopropyltryptamine (Foxy) by human liver microsomes and recombinant cytochrome P450 enzymes

2006 ◽  
Vol 71 (9) ◽  
pp. 1377-1385 ◽  
Author(s):  
Shizuo Narimatsu ◽  
Rei Yonemoto ◽  
Keita Saito ◽  
Kazuo Takaya ◽  
Takuya Kumamoto ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Oxidative Metabolism ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Cytochrome P450 Enzymes

Abstract P119: Erythrocyte n-3 and n-6 Polyunsaturated and Trans Fatty Acids and Survival of Sudden Cardiac Arrest

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Rozenn N Lemaitre ◽  
Irena B King ◽  
Catherine O Johnson ◽  
Nona Sotoodehnia ◽  
Barbara McKnight ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cardiac Arrest ◽  
Arachidonic Acid ◽  
Fatty Acid ◽  
Hospital Admission ◽  
Hospital Discharge ◽  
Trans Fatty Acid ◽  
Trans Fatty Acids ◽  
P Value ◽  
Brain Resuscitation

Lower levels of erythrocyte n-3 polyunsaturated fatty acid (PUFA) and higher levels of trans-fatty acid are associated with incident cardiac arrest (SCA) risk. However, it is not known whether these fatty acids also influence post-arrest survival. In addition, n-3 and n-6 PUFA play key roles in brain function and may be involved in brain resuscitation. We investigated the association of n-3, n-6 and trans-fatty acid levels with resuscitation outcomes in a population-based study of SCA. Subjects (mean age 68, 82% male) were out-of-hospital SCA patients found in ventricular fibrillation and attended by paramedics in King County, Washington, with available fatty acid measurements (n=492). Using logistic regression, we examined association between fatty acid levels and surviving to hospital admission (a proxy for heart resuscitation), and also to surviving to hospital discharge (a proxy for brain resuscitation). Both analyses adjusted for age; sex; race; year of cardiac arrest; time to arrival of emergency medical services; whether the event was witnessed, occurred in public, and whether bystander CPR was administered. Levels of arachidonic acid and trans-18:2 fatty acids were associated with SCA survival ( Table ). An increase of one SD in levels of arachidonic acid was associated with decreased likelihood of survival to both hospital admission and hospital discharge (OR (95% CI), uncorrected p-value: 0.75 (0.62-0.92), p =0.006 and 0.69 (0.55, 0.87), p =0.002, respectively). A one SD difference in trans-18:2 fatty acid levels was associated with decreased likelihood of survival to hospital discharge (0.74 (0.57-0.96), p =0.02)). Levels of n-3 PUFAs and trans-18:1 fatty acids were not associated with SCA survival. Our findings suggest arachidonic acid and trans-18:2 may influence SCA survival. Further work is needed to explore the role of fatty acid metabolism in heart and brain resuscitation. Association of Erythrocyte Fatty Acids with Resuscitation Outcomes Survival to hospital admission Survival to hospital discharge OR * (95% CI) p-value OR * (95% CI) p-value n-3 fatty acids α-Linolenic acid 1.01 (0.83-1.22) 0.95 0.85 (0.67-1.07) 0.60 EPA+DHA 1.05 (0.87-1.28) 0.60 1.10 (0.87-1.38) 0.44 n-6 fatty acids Linoleic acid 0.97 (0.80-1.18) 0.77 1.05 (0.83-1.33) 0.66 Arachidonic acid 0.75 (0.62-0.92) 0.006 0.69 (0.55-0.87) 0.002 Trans-fatty acids Trans-18:1 1.06 (0.87-1.29) 0.56 1.06 (0.84-1.34) 0.47 Trans-18:2 0.99 (0.80-1.22) 0.93 0.74 (0.57-0.96) 0.02 * OR corresponding to one SD higher levels

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