Document Type

Theses, Masters

Rights

Available under a Creative Commons Attribution Non-Commercial Share Alike 4.0 International Licence

Disciplines

1.4 CHEMICAL SCIENCES, 1.6 BIOLOGICAL SCIENCES

Publication Details

A thesis submitted to Technological University Dublin for the award of Master of Philosophy

Abstract

Primary Amine Oxidase (PrAO) is an enzyme with a variety of physiological roles. It catalyses the oxidative deamination of primary amines to the corresponding aldehydes. PrAO converts amines such as methylamine and aminoacetone to reactive compounds that can damage small blood vessel proteins. It also acts as a vascular adhesion protein (VAP-1) where it is essential for the migration of leukocytes through the vascular endothelium. Inhibitors of PrAO have been reported to have anti-cancer, anti-diabetic and anti-inflammatory action. In this study we explore the interaction between dietary phytochemicals and Bovine PrAO. Methylxanthines (MXs) are food alkaloids having a positive association with good health. Of several MXs we examined, only caffeine and theobromine were found to be inhibitors of PrAO. Structure activity relationships along with in silico modelling and inhibition studies allowed us to identify a unique site for MX binding to PrAO. Green Tea extracts also inhibited PrAO but these reactive compounds were shown to give complex inhibition patterns due to the formation of non-enzymatic reaction products and interference in assay procedures. Despite these difficulties we found some evidence of direct inhibition of PrAO by Green Tea catechins. A number of other compounds tested showed a similar ability to inhibit PrAO. Taken together these studies show the potential for a variety of dietary compounds to inhibit the activity of this key enzyme. The role of PrAO inhibition by such phytochemicals in health and disease is discussed.

DOI

https://doi.org/10.21427/m580-nk39

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