Contact Information Phone: 218-726-7922 Fax: 218-726-8014 Email: panderso@d.umn.edu Address: 259 SMed 1035 University Dr. Duluth, MN 55812

Professor Emeritus

Research

Research interests in my laboratory centered on regulation of expression of carbamoyl-phosphate synthetases and the urea cycle in fish; enzymology of energy metabolism in sharks; mechanism and biological role of cyanase and products of the cyn operon in Eschericia coli; mechanism of action and structure of carbamoyl-phosphate synthetase and CTP synthetase.

Teleost fish generally excrete ammonia directly into the surrounding water through their gills. However, under certain circumstances many fish do excrete significant amounts of urea and apparently have the genes for the urea cycle enzymes. The first enzyme of the pathway, carbamoyl-phosphate synthetase (CPSase III), is different than the enzyme from mammalian species; it catalyzes carbamoyl phosphate formation from glutamine, rather than from ammonia. We have isolated and characterized this enzyme from a shark (a ureoosmotic elasmobranch fish) and a bass (a teleost fish), and we have sequenced the cDNA for shark, trout, toadfish, largemouth bass and an alkaline lake-adapted tilapia CPSase III. Objectives have included characterization of expression of CPSase III by measuring the levels of CPSase III mRNA. An unusual finding is that CPSase III mRNA and enzyme activity are present in muscle of trout, bass, toadfish, and, at high levels along with all urea cycle enzymes, in the tilapia. Our longer-range objective has been to understand the regulation of expression and function of CPSase III and the urea cycle in fish. In addition, we are interested in 1) the enzymology of energy, lipid, and ketone body metabolism in shark liver and 2) the structural basis for the functional differences between CPSase III and the other CPSases.

With colleagues at Argonne National Laboratories and the University of Limoge in France we have recently determined the x-ray structure of cyanase and carried out site-directed mutagenesis to test an hypothesis about the active site.  With colleagues at the University of California, Davis, we have also recently determined the x-ray structure of CTP synthetase, work aimed at understanding the role of oligomeric structure, the nature of the glutamine binding site, and the mechanism of catalysis.

Education

Publications

Publications and Book Chapters:
M. Guilloton, M.A. Walsh, A. Joachimiak, and P.M. Anderson, "A Twin Set of Low pKa Arginines Ensures the Concerted Acid Base Catalytic Mechanism of Cyanase," in preparation.

T. Lindley, T. LaBerge, A. Hall, D. Hewett-Emmett, P.J. Walsh, and P.M. Anderson, “Sequence, Expression and Evolutionary Relationships of Carbamoyl Phosphate Synthetase I in the Toad Xenopus laevis," submitted.

J.A. Endrizzi, H. Kim, P.M. Anderson, and E.P. Baldwin, "Mechanisms of Product Feedback Regulation and Drug Resistance in Cytidine Triphosphate Synthetases from the Structure of a CTP-Inhibited Complex," Biochemistry 44, 13491-13499 (2005).

J.A. Endrizzi, H. Kim, P.M. Anderson, and E.P. Baldwin, "Crystal structure of Escherichia coli cytidine triphosphate synthetase, a nucleotide-regulated glutamine amidotransferase/ATP-dependent amidoligase fusion protein and homologue of anticancer and antiparasitic drug targets," Biochemistry 43, 6447-6463 (2004).

P.A. Wright, P.M. Anderson, W. Lei, N. Frick, W.P. Wong, and Y.K. Ip, "The Crab-Eating Frog, Rana cancrivora, up-regulates hepatic carbamoyl phosphate synthetase I activity and tissue osmolyte levels in response to increased salinity," J. Exp. Biol. 301A, 559-568 (2004).

M. Guilloton,  G.S. Espie,  and P.M. Anderson,  "What is the Role of Cyanase in Plants?" Reviews in Plant Biochemistry and Biotechnology 1, 57-79 (2002).

P.M. Anderson, M.A. Broderius, K.C. Fong, K.N.T. Tsui, S.F. Chew, and Y.K. Ip, "Glutamine Synthetase Expression in Liver, Muscle, Stomach and Intestine of Bostrichthyes sinensis in Response to a High Exogenous Ammonia Concentration," J. Exp. Biol. 205, 2053-2065 (2002).

A. Todgham, P.M. Anderson, and P.A. Wright, "Effects of Exercise on Nitrogen Excretion and Urea Cycle Enzymes in Muscle and Liver Tissues of Rainbow Trout (Oncorhynchus mykiss)," Comp. Biochem. Physiol. 129, 527-539 (2001).

P.M. Anderson, "Environmental Influences on Nitrogen Excretion:  Urea and Glutamine Synthesis," in NITROGEN EXCRETION IN FISH (P.M. Anderson and P.A. Wright, eds.), Academic Press, San Diego, pp. 239-277 (2001).

P.A. Wright and P.M. Anderson, editors, NITROGEN EXCRETION IN FISH, a Volume in the Fish Physiology Series, Academic Press, San Diego, (2001).

B.L. Lim, S.F.  Chew, P.M. Anderson, and Y.K. Ip, "Reduction in the Rates of Protein and Amino Acid Catabolism to Slow Down the Accumulation of Endogenous Ammonia: A Possible Strategy Adopted by Mudskippers (Periophthalmodon schosseri and Boleophthalmus boddaerti) During Aerial Exposure in Constant Darkness,"J. Exp. Biol. 204, 1605-1615 (2001).