This project aims at elucidating the pathophysiology of hemolytic anemias secondary to defects in red cell metabolism. We will investigate in detail the glycolytic process of the red cell """"""""in vitro"""""""" utilizing newly developed techniques that allow metabolic flow to proceed unimpeded by metabolic block. This is a novel approach to the study of red cell metabolism, that shall permit analysis of glycolysis in detail, in conditions similar to those that exist in the red cell """"""""in vivo"""""""". We will investigate in detail the biochemical changes that occur during the process of red cell aging """"""""in vivo"""""""". We will examine, through analysis of glycolytic intermediates in age-fractionated red cells, the progressive development of metabolic alterations. We will study in great detail two key enzymes of glycolysis - hexokinase and pyruvate kinase. We will attempt to clarify their molecular structure and to assess the role played by isozymic shifts in the process of molecular aging of enzymes, versus the possibility that this may result from post-translational modifications.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK026793-08
Application #
3228022
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1979-08-01
Project End
1990-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
8
Fiscal Year
1987
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
Haram, S; Carriero, D; Seaman, C et al. (1991) The mechanism of decline of age-dependent enzymes in the red blood cell. Enzyme 45:47-53
Murakami, K; Piomelli, S (1991) The isoenzymes of mammalian hexokinase: tissue specificity and in vivo decline. Adv Exp Med Biol 307:277-84
Piomelli, S; Seaman, C (1991) The mechanism of enzyme decline in the red blood cell during the ""in vivo"" aging process. Adv Exp Med Biol 307:105-13
Murakami, K; Piomelli, S (1991) Decay of mammalian hexokinase: characterization of the specific proteolytic activity. Biochim Biophys Acta 1080:83-7
Piomelli, S; Loew, T (1991) Management of thalassemia major (Cooley's anemia). Hematol Oncol Clin North Am 5:557-69