University of Illinois Urbana-Champaign

Characterization of endocannabinoid and endovanilloid metabolism by cytochrome P450 epoxygenases

Carnevale, Lauren N.

This item is closed and only viewable by specific users.

Permalink

https://hdl.handle.net/2142/109582

Description

Title
Characterization of endocannabinoid and endovanilloid metabolism by cytochrome P450 epoxygenases
Author(s)
Carnevale, Lauren N.
Issue Date
2020-11-20
Director of Research (if dissertation) or Advisor (if thesis)
Nair, Satish
Doctoral Committee Chair(s)
Nair, Satish
Committee Member(s)
  • Burke, Martin D
  • Nelson, Erik
  • Fratti, Rutilio
Department of Study
Biochemistry
Discipline
Biochemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Date of Ingest
2021-03-05T21:45:31Z
Keyword(s)
cytochrome p450, endocannabinoid
Abstract
The endocannabinoid system is composed of an expanding set of lipid signaling molecules, their biosynthetic and degradative enzymes, and the cannabinoid receptors 1 and 2 (CB1 and CB2). Anandamide (C20:4, N-acyl ethanolamine) was the first endogenous ligand to be identified. A range of ester and amide polyunsaturated fatty acid conjugates and cytochrome P450 epoxygenase derived metabolites were identified which retain activity at the receptors but have distinct biological activities. These ligands, receptors, and enzymes are collectively implicated in neuronal signaling, cardiovascular function, and the immune response. A comprehensive understanding of endocannabinoid signaling and receptor pharmacology is necessary to develop targeted therapeutics. Chapter 1 provides an introduction to the endocannabinoids, endovanilloids, and the cytochrome P450 epoxygenases. We discuss the kinetic and pharmacological characterization of the N-arachidonoyl neurotransmitter conjugates, as well as their epoxide metabolites, at CYP2J2, CB1, CB2, and the transient receptor potential vanilloid 1 channel. Then we examine virodhamine and demonstrate its inhibition of CYP2J2 in a human endothelial cell wound healing assay. Next, we investigate the effect of epoxide position on bioactivity and introduce a chemical approach to prevent isomerization of sn-2 monoacylglycerols. Chapter 2 outlines our current efforts towards the structural elucidation of lipid-associated proteins. Specifically, CYP2J2 Nanodiscs were prepared to study real-time protein dynamics using liquid phase transition electron microscopy and the expression was optimized for x-ray crystallographic studies on α/β-hydrolase domain 5 and adipose triglyceride lipase.
Graduation Semester
2020-12
Type of Resource
Thesis
Permalink
http://hdl.handle.net/2142/109582
Copyright and License Information
Copyright 2020 Lauren Carnevale

Owning Collections

Graduate Dissertations and Theses at Illinois PRIMARY
Graduate Theses and Dissertations at Illinois
Dissertations and Theses - Biochemistry