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dc.contributor.advisorChairperson, Graduate Committee: David J. Singel; Patrik R. Callis (co-chair)en
dc.contributor.authorLuchsinger, Benjamin Peteren
dc.description.abstractIn the past decade an entirely new areas of biomedical science have emerged with the recognition of the critical roles played by nitric oxide (NO) in biology. The discoveries of the role of NO in the cardiovascular systems, where it participates in regulating the tone of blood vessels and the flow of blood, raised an intriguing biochemical problem about the chemical interaction of NO and hemoglobin in blood. Historically, investigation of the interaction of NO and hemoglobin have suggested the formation of heme-Fe(II)NO hemoglobin and nitrate. Neither of these products is considered to exhibit NO-related bioactivity, thus the reaction of NO with hemoglobin was thought to quench the bioactive potential of NO. In this thesis we explore the idea that these are not the only two fates of NO in its interaction with hemoglobin. Product formation following encounters of NO and hemoglobin under various conditions of oxygenation, oxidation, and NO/heme ratios are analyzed by UV/Vis optical spectroscopy, EPR (electron paramagnetic resonance) spectroscopy, and colorimetric chemical analyses. This battery of methods enables quantification of the hemoglobin species: heme-Fe(II)NO (with distribution over the hemoglobin subunits) heme-Fe(III)NO, oxyhemoglobin, methemoglobin, deoxyhemoglobin, S-nitrosohemoglobin (SNO-hemoglobin). We present results that establish a previously unsuspected favoring of protein nitrosylation at heme and thiol positions in the reaction of oxyhemoglobin with NO. We demonstrate coupling of heme reduction/oxidation activity with thiol reactivity. We provide evidence for transfer of the NO group from heme to thiol and vice versa. We demonstrate unprecedented subunit selectivity of interactions of NO with hemoglobin. Finally, we present results that highlight the nitrite reductase activity of hemoglobin whereby nitrite, which has a significant concentration in blood, is converted to bioavailable forms of NO. Overall, the in vitro chemistry reported here provides for a complete basis for rationalizing the in vivo biochemistry required for the hemoglobin/NO system to serve as regulator of blood flow.en
dc.publisherMontana State University - Bozeman, College of Letters & Scienceen
dc.subject.lcshNitric oxideen
dc.titleChemical interaction of nitric oxide and human hemoglobinen
dc.rights.holderCopyright 2004 by Benjamin Peter Luchsingeren
thesis.catalog.ckey1146922en, Graduate Committee: David M. Dooley; Lee H. Spangler; Valerie Copieen & Biochemistry.en

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