# Biochemical Mechanism of Eicosanoid Synthesizing Enzymes

> **NIH NIH R01** · GEORGIA INSTITUTE OF TECHNOLOGY · 2022 · $270,326

## Abstract

PROJECT SUMMARY
Dietary consumption of ω-3 and ω-6 fatty acids have been linked to cardiovascular health benefits in
humans. The central hypothesis is that the cardiovascular physiological effects of ω-3 and ω-6 fatty acids
are partly mediated by the synthesis of eicosanoids via the epoxygenase (EPOX) pathway. Herein we
perform biochemical studies of some of the key enzymes in these pathways. CYP2J2 is an enzyme in
the EPOX pathway that is highly expressed in the cardiovascular system in the aortic epithelium and
cardiomyocytes. CYP2J2's primary effects are facilitated via epoxidation of ω-3 and ω-6 fatty acids into
epoxides that exert potent anti- inflammatory, vasodilatory and pro-angiogenic effects. CYP2J2 is also
implicated in cardiotoxicity of drugs. Additionally, CYP2J2 is also a membrane bound protein and exhibit
unique biochemical mechanisms that are poorly characterized and are the primary focus of the current
proposal. Our first goal is to understand allosteric modulation of CYP2J2 epoxygenase activity by ω-3
and ω-6 fatty acids and selected cardiotoxic drugs (doxorubicin, ebastine and terfenadine). Our second
goal is to examine the metabolism of ω-3 and ω-6 fatty acid derived endocannabinoids by CYP2J2. It is
predicted that similar to ω-6 endocannabinoids, the ω-3 endocannabinoids are substrates for the EPOX
enzymes producing novel bioactive epoxide mediators. The third goal is to examine how the composition
of membranes effect CYP2J2 activity. We use several novel approaches that includes detection of lipid
mediators with mass spectrometry, innovative methodologies such as Nanodiscs to solubilize CYP2J2
and provide membrane bilayer environment. We also introduce novel concepts of lipid-drug heterotropic
interactions influencing the formation of the products of these enzymes. The long-term goal of this work
is to understand the interplay of the formation of the eicosanoids from dietary fatty acids.

## Key facts

- **NIH application ID:** 10723958
- **Project number:** 7R01GM115584-06
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Aditi Das
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $270,326
- **Award type:** 7
- **Project period:** 2017-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10723958

## Citation

> US National Institutes of Health, RePORTER application 10723958, Biochemical Mechanism of Eicosanoid Synthesizing Enzymes (7R01GM115584-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10723958. Licensed CC0.

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