Abstract

The goal of the research program is to study the structure, synthesis and processing of mitochondrial and cytosolic phosphoenolpyruvate carboxykinase. This will involve sequencing the enzyme protein as well as cloning a cDNA to the phosphoenolpyruvate carboxykinase mRNA using recombinant DNA procedures. Information on the structure of the enzyme will allow us to better understand its function, expecially its regulation by cofactors such as metal ions (Mn2+, Fe2+). Phosphoenolpyruvate carboxykinase is unique since, in most species, it is present in both the cytosol and mitochondria. The synthesis, transport and processing of the mitochondrial enzyme will be studied and compared to the cytosol isozyme in order to better understand the coordinate regulation of gene expression. Since phosphoenolpyruvate carboxykinase is a key, pacesetting enzyme in both hepatic and renal gluconeogenesis, our findings will contribute to a better understanding of the regulation of glucose homeostasis in verebrates and allow us to draw analogies to the regulation of both forms of the enzyme in disease processes such as diabetes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37DK021859-11
Application #
3483401
Study Section
Biochemistry Study Section (BIO)
Project Start
1978-07-01
Project End
1991-12-31
Budget Start
1989-01-01
Budget End
1989-12-31
Support Year
11
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Case Western Reserve University
Department
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106

  Publications

Nye, Colleen K; Hanson, Richard W; Kalhan, Satish C (2008) Glyceroneogenesis is the dominant pathway for triglyceride glycerol synthesis in vivo in the rat. J Biol Chem 283:27565-74
Liu, G; Molas, M; Grossmann, G A et al. (2001) Biological properties of poly-L-lysine-DNA complexes generated by cooperative binding of the polycation. J Biol Chem 276:34379-87
Savon, S P; Hakimi, P; Crawford, D R et al. (1997) The promoter regulatory regions of the genes for the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) from the chicken and the rat have different species-specific roles in gluconeogenesis. J Nutr 127:276-85
Perales, J C; Grossmann, G A; Molas, M et al. (1997) Biochemical and functional characterization of DNA complexes capable of targeting genes to hepatocytes via the asialoglycoprotein receptor. J Biol Chem 272:7398-407
Ferkol, T; Perales, J C; Mularo, F et al. (1996) Receptor-mediated gene transfer into macrophages. Proc Natl Acad Sci U S A 93:101-5
Nizielski, S E; Lechner, P S; Croniger, C M et al. (1996) Animal models for studying the genetic basis of metabolic regulation. J Nutr 126:2697-708
Patel, Y M; Yun, J S; Liu, J et al. (1994) An analysis of regulatory elements in the phosphoenolpyruvate carboxykinase (GTP) gene which are responsible for its tissue-specific expression and metabolic control in transgenic mice. J Biol Chem 269:5619-28
Hanson, R W; Patel, Y M (1994) Phosphoenolpyruvate carboxykinase (GTP): the gene and the enzyme. Adv Enzymol Relat Areas Mol Biol 69:203-81
Perales, J C; Ferkol, T; Molas, M et al. (1994) An evaluation of receptor-mediated gene transfer using synthetic DNA-ligand complexes. Eur J Biochem 226:255-66
Perales, J C; Ferkol, T; Beegen, H et al. (1994) Gene transfer in vivo: sustained expression and regulation of genes introduced into the liver by receptor-targeted uptake. Proc Natl Acad Sci U S A 91:4086-90

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