Ph.D., Molecular Biology, University of Pennsylvania School of Medicine, 2003
B.S., Biology, Massachusetts Institute of Technology, 1986
The overall goal of my research is to provide a better understanding of energy metabolism in the pathogenic protist Entamoeba histolytica. This microbe is a scavenger that lacks ATP-generating mitochondria and hydrogenosomes as well as many common metabolic pathways. Thus, glycolysis is thought to be a primary pathway for ATP production. Glycolysis and the downstream conversion of pyruvate to acetyl-CoA and subsequently to acetate are atypical in several ways in E. histolytica. The glycolytic enzymes phosphofructokinase and pyruvate kinase are replaced by PPi-dependent phosphofructokinase and PPi-dependent pyruvate phosphate dikinase, and pyruvate:ferredoxin oxidoreductase replaces pyruvate dehydrogenase for conversion of pyruvate to acetyl-CoA. As acetyl-CoA cannot enter the citric acid cycle, ADP-forming acetyl-CoA synthetase (Ads) is present in E. histolytica to break down acetyl-CoA to generate additional ATP and recycle CoA. In addition, a PPi-forming acetate kinase (Ack) is present that may serve to supply PPi for glycolysis. My research focuses on the enzymology and physiological role of Ads and Ack.
TM Thaker, M Tanabe, ML Fowler, AM Preininger, C Ingram-Smith, KS Smith, and TM Iverson. 2013. Crystal structures of acetate kinases from the eukaryotic pathogens Entamoeba histolytica and Cryptococcus neoformans. Journal of Structural Biology 181:185-189.
M Fowler, C Ingram-Smith, and KS Smith. 2012. Novel pyrophosphate-forming acetate kinase from the protist Entamoeba histolytica. Eukaryotic Cell 11:1249-1256.
M Fowler, C Ingram-Smith, and KS Smith. 2011. Characterization of a novel pyrophosphate-dependent acetate kinase from Entamoeba histolytica. Journal of Visualized Experimentation
C Ingram-Smith, SR Martin, and KS Smith. 2006. Acetate kinase: not just a bacterial enzyme. Trends in Microbiology 14:249-253.
C Ingram-Smith, A Gorrell, P Iyer, KS Smith, and JG Ferry. 2005. The acetate-binding pocket of the Methanosarcina thermophila acetate kinase. Journal of Bacteriology 187:2386-2394.