Detailed studies of structure-reactivity in the binding of dioxygen, carbon monoxide, isocyanides, nitric oxide and nitrogen and oxygen bases to heme protein model compounds will be made. Special attention will be given to the picosecond kinetics in these systems. These studies will provide the mechanisms of the fundamental binding processes with iron(II) porphyrins in the absence of proteins. In this way the protein effects can be separated from the basic chemical effects in the dynamic processes occurring in oxygen transport. Secondly, these systems provide new approaches to the study of details of solvent-geminate pair dynamics of broader significance. To complete the study of geminate processes the picosecond relaxation after photolysis of free radical cage precursors such as porphyrin metal-alkyl complexes and ketenimines, R2C=C=N-R' will also be examined. To understand the biological effects of nitric oxide interactions, detailed equilibrium and second to picosecond kinetic studies of model heme-NO complexes will be studied. Structural and environmental effects on NO binding kinetics and equilibria and on the formation of Heme-NO from Base-Heme-NO will be studied in detail. The effect of pH on NO binding, proximal base dissociation and picosecond NO kinetics will be studied with myoglobin and other heme proteins. New model systems designed to mimic the proteins ascaris hemoglobin and peroxidases which have highly polar pockets will be prepared. These models will provide basic structural effects needed in the current discussions of the effects of polarity in protein behavior.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL013581-28
Application #
2214756
Study Section
Metallobiochemistry Study Section (BMT)
Project Start
1979-02-01
Project End
1997-06-30
Budget Start
1995-07-01
Budget End
1996-06-30
Support Year
28
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Peterson, Linda R; Herrero, Pilar; McGill, Janet et al. (2008) Fatty acids and insulin modulate myocardial substrate metabolism in humans with type 1 diabetes. Diabetes 57:32-40
Saeed, Ibrahim M; Barry, Michael; Peterson, Linda R et al. (2007) Positron emission tomography imaging in the cardiometabolic syndrome. J Cardiometab Syndr 2:67-9
Peterson, Linda R; Soto, Pablo F; Herrero, Pilar et al. (2007) Sex differences in myocardial oxygen and glucose metabolism. J Nucl Cardiol 14:573-81
de las Fuentes, Lisa; Brown, Angela L; Mathews, Santhosh J et al. (2007) Metabolic syndrome is associated with abnormal left ventricular diastolic function independent of left ventricular mass. Eur Heart J 28:553-9
Cresci, Sharon; Gropler, Robert J (2007) Image-guided cardiovascular functional genomics: finding the needle in the haystack. J Nucl Cardiol 14:275-6
Glover, David K; Gropler, Robert J (2007) Journey to find the ideal PET flow tracer for clinical use: are we there yet? J Nucl Cardiol 14:765-8
Herrero, Pilar; Peterson, Linda R; McGill, Janet B et al. (2006) Increased myocardial fatty acid metabolism in patients with type 1 diabetes mellitus. J Am Coll Cardiol 47:598-604
Peterson, Linda R; Waggoner, Alan D; de las Fuentes, Lisa et al. (2006) Alterations in left ventricular structure and function in type-1 diabetics: a focus on left atrial contribution to function. J Am Soc Echocardiogr 19:749-55
Srinivasan, Muthayyah; Herrero, Pilar; McGill, Janet B et al. (2005) The effects of plasma insulin and glucose on myocardial blood flow in patients with type 1 diabetes mellitus. J Am Coll Cardiol 46:42-8
Herrero, Pilar; Dence, Carmen S; Sharp, Terry L et al. (2004) Impact of reversible trapping of tracer and the presence of blood metabolites on measurements of myocardial glucose utilization performed by PET and 18F-fluorodeoxyglucose using the Patlak method. Nucl Med Biol 31:883-92

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