Graduation date: 1993

Thesis (Ph. D.)--West Virginia University, 2008. / Title from document title page. Document formatted into pages; contains xiii, 110 p. : ill. (some col.) + 4 video files. Includes four QuickTime video files. Vita. Includes abstract. Includes bibliographical references (p. 109-110) and index.

Thesis (doctoral)--University of Helsinki, 1990. / Includes bibliographical references (p. 50-64).

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Work on developing an instrumental system for total analysis of triglycerides and phospholipids is presented. Initial chromatographic analysis using reversed-phase high performance liquid chromatography on C(,6)-bonded, 5 (mu)m silica stationary phase and acetonitrile-water (and dilute phosphoric acid with phospholipids) mobile phase is demonstrated. The Kovats index is shown to allow correlation of structure to retention behavior. An ultraviolet absorbance detector ((lamda)(,195m,)) and novel post-column reaction detector (p.c.r.) based on saponification, periodate oxidation and derivatization using a new class of reagents are used for detection. The p.c.r. is shown to be sensitive to samples in the lower nanomole-per-injection range. / A novel transport-thermal ionic detector for organophosphorus compounds and a new class of aldehyde reagents are introduced. The detector is capable of detecting some pesticides in the lower nanogram-per-injection range. The aldehyde reagents, called the Fluorals, of which Fluoral-P (4-amino-3-penten-2-one) is studied extensively, have promise of being useful for selective, rapid and sensitive (sub-nanomoles formaldehyde) determinations.

Metabolic Syndrome (MetS) is an obesity-related disorder that predisposes an individual to several life-threatening diseases such as cardiovascular disease, hypertension and type 2 diabetes mellitus. The diagnosis of metabolic syndrome is based on the presence of at least 3 of the following 5 risk factors: elevated triglycerides, high blood pressure, high blood glucose, low HDL cholesterol and central adiposity. However, the biochemical mechanisms underlying the contribution of these irregularities are not fully understood. Currently, there is a need to better characterize MetS. Irregularity of lipid abundances, dyslipidemia, is known to be associated with MetS. However, little is known about the link between plasma phospholipids and human metabolic syndrome. In this study, mass spectrometry-based metabolomic approaches were employed using ultrahigh-resolution FTICR mass spectrometry to qualitatively analyze human plasma phospholipids and high-resolution QTOF mass spectrometry to quantitatively detect differences in the human plasma phospholipid profiles from 10 clinically-diagnosed metabolic syndrome patients and 8 lean healthy controls. The results point to the existence of a phospholipid signature of MetS. Five of the top twenty phospholipids contributing most to the difference in phospholipid abundance between the MetS and control group were identified using accurate mass-based database searching and MS/MS for structural confirmation. Relative differences in phospholipid abundances between MetS and controls for all top 20 phospholipids were shown to be statistically significant. These results may aid biomarker discovery and the accurate evaluation and prevention of diseases associated with dyslipidemia including human metabolic syndrome. / Graduate

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The aim of this project is to characterise the levels of cholesterol and phospholipid in cell homogenates, plasma membranes and isolated membrane domains from wildtype (WT) and caveolin-l knock-out (Cav-1-/ -) mouse embryonic fibroblasts (MEFs). Quantitative lipid analysis was developed for cholesterol by high-performance liquid chromatography (HPLC) and for glycerophospholipids (GPL) and sphingomyelin (SM) by electrospray ionisation mass spectrometry (ESI-MS). In the cell homogenates, by comparing WT to Cav-l-/- MEFs, it was found that the total cholesterol as well as the proportions of the main GPLs such as Phosphatidylcholines (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS) was similar in both cell types. However, Cav-l-/- MEFs have higher levels of cholesterol esters than WT MEFs in whole cell homogenate. Furthermore, the proportion of SM is higher in Cav-l-/- than WT MEFs. These data suggest that Cav-l may control the balance between free and esterified cholesterol and is involved in SM metabolism. A small increase in SM level in Cav-l-/- compared to WT plasma membrane was observed but this increase was not significant. Similarly, cholesterol levels in the plasma membrane are comparable between the two cell types. In both cell types, the levels of SM and phosphatidylglycerol (PG) are higher in the plasma membranes than in cell homogenates. In the WT cells, PE levels are higher in the plasma membrane than in the cell homogenates. While in the Cav-1-/- cells, the level of free cholesterol and PC are higher in the plasma membrane compared to the cell homogenate. PCs are the predominant lipids in both cell types. Cav-1-l - cells have more saturated fatty acyl chains in their PC species and shorter carbon chains compared to WT MEFs and this trend was found in both cell homogenate and plasma membranes. In PEs and SMs, Cav-1-/ - cells also have higher levels of saturated PEs and saturated amide-linkage SM than in WT cells, respectively. The results indicate that Cav-1 may also play a role in fatty acids metabolism. In summary, the data from this work indicate that Cav-l expression affects lipid composition in MEFs including the relative distribution of free and esterified cholesterol, the levels of SM relative to other phospholipid subclasses and the incorporation of fatty acids into phospholipids.