• Food chemistry and toxicology;
• impact of diet on metabolic systems;
• application of LC/MS/MS in the identification and occurrence flavonoids and flavonoid metabolites in foods and biological tissues

EDUCATION:

1990   B.S., Environmental Toxicology - Honors, University of California, Davis
1996   Ph.D., Pharmacology and Toxicology, University of California, Davis

POSITIONS HELD:

Research Assistant, Department of Environmental Toxicology, UC Davis, Davis, California, 1991-92
Research Assistant, Facility for Advanced Instrumentation, UC Davis, Davis, California, 1992-96
Postdoctoral Research Fellow, Department of Nutrition, UC Davis, Davis, California, 1996-99
Adjunct Assistant Professor, Department of Environmental Toxicology, UC Davis, Davis, California, 1999-00
Assistant Professor and Food Chemist, Department of Food Science and Technology, UC Davis, Davis, California, 2000 - present

RESEARCH OBJECTIVES - LAY TERMS

In order to better understand how diet impacts health, our laboratory focuses on the development of new methodologies that allow for the assessment of how dietary and environmental factors impact metabolic pathways. In order to maintain the nutritive quality of foods, we also focus on advancing new approaches for characterizing the phytochemical composition of foods. These methods allow us to assess how postharvest processing (e.g. microwaving and baking) and agricultural conditions impact levels of phytochemicals and allow us to develop strategies that enhance levels of beneficial phytochemicals in foods.

RESEARCH OBJECTIVES - FOR PEERS

My research program is focused on (1) the development and application of bioanalytical mass spectrometry methodologies for the characterization and quantitation of biotransformation enzymes, and in vivo protein modification indicative of oxidative stress in response to dietary and environmental factors, (2) the characterization and quantitation of flavonoids and their metabolites in biological matrices and (3) the characterization and quantitation of flavonoids in foods and determining how mechanical processes (e.g., processing and storage) and agricultural conditions affect phytochemical profiles in foods.

My research strengths are in analytical chromatography and liquid mass spectrometry. We are currently developing hybrid LC/MS/MS methods to quantitate key biotransformation enzymes directly in tissue homogenates. We are particularly interested in a family of enzymes called the glutathione S-transferases (GSTs) because these enzymes are the bodyÕs most important defensive system with respect to detoxifying chemical carcinogens and toxic products of lipid peroxidation. These studies are accomplished using a state-of the-art triple quadrupole mass spectrometer interfaced (Z-Spay geometry) to an automated LC system. We use techniques such as select ion monitoring (SIM) to increase selectivity and sensitivity of the instrument. SIMs works by increasing the time the MS spends scanning specific ions which improves the signal-to-noise ration and increases sensitivity. Proteins such as the GSTs can be selectively measured by monitoring molecular ions corresponding to different charge states of the protein. Essentially this gives several independent measurements of the same protein and greatly improves selectivity.

Our laboratory is also involved in developing methods to generate metabolites of key flavonoids (e.g. epicatechin, catechin, quercetin) commonly present in fruits, and establishing quantitative LC/MS/MS techniques for their identification in biological matrices so that their bioavailability can be assessed in vivo. To date, understanding the bioavailability of flavonoids has been hampered by analytical constraints and a lack of flavonoid metabolite standards. Therefore, we are developing LC/MS/MS combination strategies employing SIM techniques to monitor flavonoids and their metabolite(s) in biological samples. These approaches represent significant advantages over traditional methodologies in that they are unambiguous and allow for the simultaneous measure of up to 32 products in a biological sample at one time.

SELECTED PUBLICATIONS:

• Purification, mass spectrophotometric characterization, and covalent modification of murine glutathione S-transferases. A.E. Mitchell et al. 1995. Chemical Research in Toxicology 8:1054-1062.
• Haloenol lactone is a new isozyme-selective and active site-directed inactivator of glutathione S-transferase. J. Zheng et al. 1996. Journal of Biological Chemistry 271:20421-20425.
• Structural and functional consequences of haloenol lactone inactivation of murine and human glutathione S-transferase. A.E. Mitchell et al. 1997. Biochemistry 37:6752-6759.
• Quantitative profiling of tissue- and gender-related expression of glutathione S-transferase isozymes in the mouse. A.E. Mitchell et al. 1997. Biochemical Journal 325:207-216.
• Inhibition of glutathione transferase by haloenol lactones. J. Zheng et al. 1998. U.S. Patent #5,767,147.
• Identification of procyanidins in cocoa (Theobroma cacao) and chocolate using high-performance liquid chromatography/mass spectrometry. J.F. Hammerstone et al. 1999. Journal of Agricultural and Food Chemistry 47:490-496.
• Characterization of pyrroloquinoline quinone amino acid derivatives by electrospray ionization mass spectrometry and detection in human milk. A.E. Mitchell et al. 1999. Analytical Biochemistry 269:317-325.
• HPLC method for the quantification of procyanidins in cocoa and chocolate samples and correlation to total antioxidant capacity. G.E. Adamson et al. 1999. Journal of Agricultural and Food Chemistry 47:4184-4188.
• Determination of antioxidant properties of aroma extracts isolated from various beans. K.-G. Lee et al. 2000 Journal of Agriculture and Food Chemistry 48:4817-4820
• The impact of agricultural practices and drying methods on the composition of procyanidins in fruits and vegetables. Y.-J. Hong, D. Asami, D. Barrett and A.E. Mitchell. 2002 (in consideration by the Journal of Agriculture and Food Chemistry).
• Processing induced changes in phenolic antioxidants and procyanidins in clingstone peaches. D. Asami, Y.-J. Hong, D. Barrett and A.E. Mitchell. 2002 (in consideration by the Journal of the Science of Food and Agriculture)