This research is directed towards increasing understanding of normal and abnormal erythrocyte and leukocyte metabolism and towards elucidating the pathogenesis of both hereditary and acquired homolytic anemias. The enzymatic behavior and constituents of separated red cells and white cells are being investigated in hemolysates and homogenates, before or after incubation with added substances by spectrophotometric methods in most instances. Metabolic studies of the pentose phosphate pathway and recycling in intact cells are being performed with radioactive labeled compounds utilizing the ionization chamber method. The objectives are to extend knowledge of pyruvate kinase deficiency and other enzyme deficiency hemolytic anemias with particular reference to genetic polymorphism, to define new enzymopenic hemolytic disorders, to examine further the role of the pentose phosphate pathway in various enzyme deficiency hemolytic anemias, especially during oxidant forms of stress, to enlarge understanding of certain acquired hemolytic anemias,k and to utilize as metabolic models the red cell and white cell, since they are easily sampled and may reflect metabolic abnormalities or changes occurring in the other less accessible tissue due to an hereditary metabolic defect, systemic disease, or administration of drugs. These studies should provide a better basis for understanding normal and abnormal red cell and white cell metabolism and lead to improved diagnosis and therapy of clinical disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK014898-26
Application #
3225314
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1976-01-01
Project End
1991-04-30
Budget Start
1988-05-01
Budget End
1989-04-30
Support Year
26
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Los Angeles County Harbor-UCLA Medical Center
Department
Type
DUNS #
City
Torrance
State
CA
Country
United States
Zip Code
90509
Zerez, C R; Lachant, N A; Lent, K M et al. (1992) Decreased pyrimidine nucleoside monophosphate kinase activity in sickle erythrocytes. Blood 80:512-6
Lachant, N A; Zerez, C R; Barredo, J et al. (1991) Hereditary erythrocyte adenylate kinase deficiency: a defect of multiple phosphotransferases? Blood 77:2774-84
Tanaka, K R; Zerez, C R (1990) Red cell enzymopathies of the glycolytic pathway. Semin Hematol 27:165-85
Zerez, C R; Lachant, N A; Tanaka, K R (1990) Impaired erythrocyte methemoglobin reduction in sickle cell disease: dependence of methemoglobin reduction on reduced nicotinamide adenine dinucleotide content. Blood 76:1008-14
Zerez, C R; Wong, M D; Tanaka, K R (1990) Partial purification and properties of nicotinamide adenine dinucleotide synthetase from human erythrocytes: evidence that enzyme activity is a sensitive indicator of lead exposure. Blood 75:1576-82
Zerez, C R; Lachant, N A; Tanaka, K R (1989) Decreased erythrocyte phosphoribosylpyrophosphate synthetase activity and impaired formation in thalassemia minor: a mechanism for decreased adenine nucleotide content. J Lab Clin Med 114:43-50
Zerez, C R; Tanaka, K R (1989) Impaired erythrocyte NAD synthesis: a metabolic abnormality in thalassemia. Am J Hematol 32:1-7
Lachant, N A; Zerez, C R; Tanaka, K R (1989) Pyrimidine nucleotides impair phosphoribosylpyrophosphate (PRPP) synthetase subunit aggregation by sequestering magnesium. A mechanism for the decreased PRPP synthetase activity in hereditary erythrocyte pyrimidine 5'-nucleotidase deficiency. Biochim Biophys Acta 994:81-8
Lachant, N A; Zerez, C R; Tanaka, K R (1989) Relationship between the nicotinamide adenine dinucleotide redox potential and the 2,3-diphosphoglycerate content in the erythrocyte in sickle cell disease. Br J Haematol 72:265-71
Zerez, C R; Wong, M D; Lachant, N A et al. (1988) Impaired erythrocyte phosphoribosylpyrophosphate formation in hemolytic anemia due to pyruvate kinase deficiency. Blood 72:500-6