Year of Publication

2010

Degree Name

Doctor of Philosophy (PhD)

Document Type

Dissertation

College

Arts and Sciences

Department

Chemistry

First Advisor

Dr. Bert C. Lynn

Abstract

The focus of this dissertation is centered on the mass spectral analysis of lipids and changes occurring in keeping with the concept of homeoviscous adaptation [1]. Homeoviscous adaptation is the process of modification of membrane lipids in response to environmental stimuli [1]. Dissertation investigations applied this concept to prokaryotic and eukaryotic organisms, and expanded the perception of environmental factors from exogenous organic solvents to intracellular environment.

The field of lipidomics deals with the analysis of phospholipid and fatty acid components of membranes the changes that occur due to environmental stimuli and their biological significance [2-6]. The high sensitivity of mass spectrometry (MS) is an ideal tool for lipidomics allowing detection, quantification and structural elucidation [6]. Coupling of a mass spectrometer to a chromatographic system, such as gas chromatograph (GC), allows the separation of fatty acid methyl esters analytes prior to analysis [7].

The research investigations that comprise this dissertation are divided into three interrelated projects. The first project involved the analysis of composition and structure of Clostridium thermocellum membranes from wild-type and ethanol-adapted strains in response to adaptation of cultures to growth in ethanol. The hypothesis being that adaptation of cultures to growth in ethanol would result in compensatory change to the membrane composition.

Rat mitochondrial fatty acid profiles isolated from brain, liver, kidney and heart tissues were compared. The hypothesis being that differences in cellular environments found among various tissues would be reflected in the mitochondrial membrane composition. These data support the concept that variations to the lipid content of neurological mitochondria may increase susceptibility to the products of oxidative stress.

Lastly, changes in neurological mitochondria as a function of Alzheimer’s disease progression were studied. The hypothesis being that changes to the mitochondrial lipidome would be significantly reflected during advanced stages of AD, in addition to being more prevalent in regions displaying greater pathology.

The three interrelated projects increased our understanding of the boundaries established by the concept of homeoviscous adaptation. Project specific hypotheses were supported by data obtained from these investigations.

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