Dean R. Appling

dappling@mail.utexas.edu
Biochemistry
Associate Department Chair, Chairman's Office
Professor, Faculty
Lester J. Reed Professorship in Biochemistry
Dean R. Appling

Contact Information

Office
WEL 4.230D
Office Phone
471-5842
Lab
WEL 4.244
Lab Phone
471-6836
Fax
471-5849

Research Group

Appling Lab

Education

BS Biology, Texas A&M University (1977);   PhD Biochemistry, Vanderbilt University (1981); Postdoctorate, University of California - Berkeley (1981-85)

Regulation and organization of metabolic pathways

Eukaryotic cells are composed of many different compartments, such as mitochondria and nuclei. Although each of these compartments exhibits a distinct set of metabolic processes, they must all communicate with each other for the cell to function properly. Understanding how these processes are organized and controlled represents the next frontier in the study of metabolism. We have focused our efforts on folate-mediated one-carbon metabolism. This set of pathways is found in all cells and organisms, is central to fundamental processes such as nucleic acid and protein synthesis, and occurs in multiple compartments. We utilize a wide variety of biochemical and molecular genetic techniques, as well as nuclear magnetic resonance, to study the organization of these pathways in both mammalian and yeast systems. The use of noninvasive techniques such as NMR has revealed metabolic relationships and interactions that were overlooked in traditional in vitro systems.

The molecular organization of a metabolic pathway is ultimately dependent on the unique three-dimensional structures of the individual enzyme components. Thus, we have several protein structure projects ongoing in the laboratory. Techniques include kinetic analysis, site-directed mutagenesis, and X-ray crystallography (in collaboration with Dr. Robertus). Our goal is to understand how these enzymes function and interact with one another in the cell.

Representative Publications

  • Lu, P., Rangan, A., Chan, S.Y., Appling, D.R., Hoffman, D.W., and Marcotte, E.M.  "Global metabolic changes following loss of a feedback loop reveal dynamic steady states of the yeast metabolome" Metab Eng. 9 (2007): 8-20. View Publication

  • Walkup, A.S. and Appling. D.R.  "Enzymatic characterization of human mitochondrial C1-tetrahydrofolate synthase" Arch Biochem Biophys. 442 (2005): 196-205. View Publication

  • Wagner, W., Breksa, A.P. III, Monzingo, A.F., Appling, D.R. and Robertus, J.D.  "Kinetic and Structural Analysis of Active Site Mutants of Monofunctional NAD-Dependent 5,10-Methylenetetrahydrofolate Dehydrogenase from Saccharomyces cerevisiaeBiochemistry 44 (2005): 13163-13171. View Publication

  • Suliman, H.S., Sawyer, G.M., Appling. D.R., and Robertus, J.  "Purification and properties of cobalamin-independent methionine synthase from C. albicans and S. cerevisiaeArch Biochem Biophys. 441 (2005): 56-63. View Publication

  • Garofalo, C., Kramer, G., and Appling, D.R.  "Characterization of the C2 Subdomain of Yeast Mitochondrial Initiation Factor 2" Arch. Biochem. Biophys. 439 (2005): 113-120. View Publication