Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 100, Issue 20, Pages 11303-11308Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2033883100
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Funding
- NHLBI NIH HHS [R37 HL058091, R29 HL058091, HL58091, R01 HL058091] Funding Source: Medline
- NIBIB NIH HHS [P41 EB001980, EB001980] Funding Source: Medline
- NIGMS NIH HHS [GM55792, R29 GM055792, R01 GM055792] Funding Source: Medline
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Nitric oxide has been proposed to be transported by hemoglobin as a third respiratory gas and to elicit vasodilation by an oxygen-linked (allosteric) mechanism. For hemoglobin to transport nitric oxide bioactivity it must capture nitric oxide as iron nitrosyl hem:)globin rather than destroy it by dioxygenation. Once bound to the heme iron, nitric oxide has been reported to migrate reversibly from the heme group of hemoglobin to the beta-93 cysteinyl residue, in response to an oxygen saturation-dependent conformational change, to form an S-nitrosothiol. However, such a transfer requires redox chemistry with oxidation of the nitric oxide or beta-93 cysteinyl residue. in this article, we examine the ability of nitric oxide to undergo this intramolecular transfer by cycling human hemoglobin between oxygenated and deoxygenated states. Under various conditions, we found no evidence for intra molecular transfer of nitric oxide from either cysteine to heme or home to cysteine. In addition, we observed that contaminating nitride can lead to formation of iron nitrosyl hemoglobin in deoxygen ated hemoglobin preparations and a radical in oxygenated hemoglobin preparations. Using N-15-labeled nitrite, we clearly demonstrate that nitrite chemistry could explain previously report d results that suggested apparent nitric oxide cycling from hem to thiol. Consistent with our results from these experiments conducted in vitro, we found no arterial/venous gradient of iron nitrosyl hemoglobin detectable by electron paramagnetic resonance spectroscopy. Our results do not support a role for allosterically controlled intramolecular transfer of nitric oxide in hemoglobin as a function of oxygen saturation.
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