Model compounds for hemoglobin and related hemoproteins will be prepared and the effect of their structure on the dynamics of reaction with dioxygen, carbon monoxide, and isonitriles studied. Cyclophane heme compounds displaying distal side steric effect will be studied by structural, spectroscopic and kinetic methods in order to define the nature of the distal side steric effect. New ortho-substituted tetraphenylheme derivatives will be prepared and their interaction with CO and dioxygen studied in order to define the new phenomenon of heme rigidity and its effect on ligand binding. Synthetic heme compounds already demonstrated to show cooperativity and pH-dependent binding will be studied by computer modeling and by titration and kinetic methods. Flash photolysis of heme complexes will be studied by FTIR methods to obtain flash IR spectra of unstable intermediates. Similar studies by flash resonance Raman spectra will be undertaken in order to describe the relaxation processes occurring in protein-free active sites. This study will define those characteristics of heme compounds and their environment which control the varied reactivities of such hemes in hemoproteins. This information will provide the means of understanding the cooperativity in hemoglobin and other biomolecular reactions and will allow synthetic oxygentransporting materials, for use as blood substitutes, to be prepared.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Metallobiochemistry Study Section (BMT)
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University of California San Diego
Schools of Arts and Sciences
La Jolla
United States
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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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