Abstract

Our long term goal is to understand the control mechanisms of carbohydrate metabolism in various mammalian tissues and yeast. Specifically, we are interested in the regulation of phosphofructokinase, one of the key enzymes of glycolysis. Currently we are investigating the physiological importance of a covalent modification of phosphofructokinase in liver and heart. We are also studying the roles of fructose-2, 6-P2, a recently discovered potent activator of phosphofructokinase. Synthesis and degradation of fructose-2,6-P2 is catalyzed by a bifunctional enzyme, fructose-6-P,2-kinase and fructose-2,6-bisphosphatase. We plan to purify and characterize heart fructose-6-P, 2- kinase:fructose-2, 6-bisphosphatase. The study of the structure and the function of the liver bifunctional enzyme will be continued. Of particular interest with this bifunctional enzyme is phosphorylation which leads to opposite activities depending on the tissue sources. Using perfused heart and isolated myocytes the physiological significance of phosphorylation will be investigated as well as the effects of various alpha and beta agonists and cardiac work on the bifunctional enzymes and also on phosphofructokinase will be studied.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK016194-20
Application #
3225560
Study Section
Biochemistry Study Section (BIO)
Project Start
1977-08-01
Project End
1992-07-31
Budget Start
1991-08-01
Budget End
1992-07-31
Support Year
20
Fiscal Year
1991
Total Cost
Indirect Cost

  Institution

Name
University of Texas Sw Medical Center Dallas
Department
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390

  Publications

Jin, Eunsook S; Sherry, A Dean; Malloy, Craig R (2009) Evidence for reverse flux through pyruvate kinase in skeletal muscle. Am J Physiol Endocrinol Metab 296:E748-57
van Zijl, Peter C M; Jones, Craig K; Ren, Jimin et al. (2007) MRI detection of glycogen in vivo by using chemical exchange saturation transfer imaging (glycoCEST). Proc Natl Acad Sci U S A 104:4359-64
Jin, Eunsook S; Park, Byung-Hyun; Sherry, A Dean et al. (2007) Role of excess glycogenolysis in fasting hyperglycemia among pre-diabetic and diabetic Zucker (fa/fa) rats. Diabetes 56:777-85
Jin, Eunsook S; Jones, John G; Burgess, Shawn C et al. (2005) Comparison of [3,4-13C2]glucose to [6,6-2H2]glucose as a tracer for glucose turnover by nuclear magnetic resonance. Magn Reson Med 53:1479-83
Jin, Eunsook S; Jones, John G; Merritt, Matthew et al. (2004) Glucose production, gluconeogenesis, and hepatic tricarboxylic acid cycle fluxes measured by nuclear magnetic resonance analysis of a single glucose derivative. Anal Biochem 327:149-55
Jin, Eunsook S; Uyeda, Kosaku; Kawaguchi, Takumi et al. (2003) Increased hepatic fructose 2,6-bisphosphate after an oral glucose load does not affect gluconeogenesis. J Biol Chem 278:28427-33
Lee, Yong-Hwan; Li, Yang; Uyeda, Kosaku et al. (2003) Tissue-specific structure/function differentiation of the liver isoform of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase. J Biol Chem 278:523-30
Kawaguchi, T; Veech, R L; Uyeda, K (2001) Regulation of energy metabolism in macrophages during hypoxia. Roles of fructose 2,6-bisphosphate and ribose 1,5-bisphosphate. J Biol Chem 276:28554-61
Sakurai, M; Cook, P F; Haseman, C A et al. (2000) Glutamate 325 is a general acid-base catalyst in the reaction catalyzed by fructose-2,6-bisphosphatase. Biochemistry 39:16238-43
Wu, R F; Uyeda, K (1999) Mutations in the charged residues of the amino terminus of rat liver fructose 6-phosphate,2-kinase:Fructose 2,6-bisphosphatase: effects on regulation. Arch Biochem Biophys 371:15-23

Showing the most recent 10 out of 36 publications