Kinetic feasibility of nitroxyl reduction by physiological reductants and biological implications

Matthew I. Jackson, Tae H. Han, Laura Serbulea, Andrew Dutton, Eleonora Ford, Katrina M Miranda, K. N. Houk, David A. Wink, Jon M. Fukuto

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Nitroxyl (HNO), the one-electron reduced and protonated congener of nitric oxide (NO), is a chemically unique species with potentially important biological activity. Although HNO-based pharmaceuticals are currently being considered for the treatment of chronic heart failure or stroke/transplant-derived ischemia, the chemical events leading to therapeutic responses are not established. The interaction of HNO with oxidants results in the well-documented conversion to NO, but HNO is expected to be readily reduced as well. Recent thermodynamic calculations predict that reduction of HNO is biologically accessible. Herein, kinetic analysis suggests that the reactions of HNO with several mechanistically distinct reductants are also biologically feasible. Product analysis verified that the reductants had in fact been oxidized and that in several instances HNO had been converted to hydroxylamine. Moreover, a theoretical analysis suggests that in the reaction of HNO with thiol reductants, the pathway producing sulfinamide is significantly more favorable than that leading to disulfide. Additionally, simultaneous production of HNO and NO yielded a biphasic oxidative capacity.

Original languageEnglish (US)
Pages (from-to)1130-1139
Number of pages10
JournalFree Radical Biology and Medicine
Volume47
Issue number8
DOIs
StatePublished - Oct 15 2009

Fingerprint

Reducing Agents
Nitric Oxide
Kinetics
Transplants
Hydroxylamine
Bioactivity
Thermodynamics
Sulfhydryl Compounds
Oxidants
Disulfides
Ischemia
Heart Failure
Stroke
Electrons
Pharmaceutical Preparations
nitroxyl
Therapeutics

Keywords

  • Free radicals
  • Kinetics
  • Nitric oxide
  • Nitrogen oxides
  • Nitroxyl
  • Reduction
  • Thiols

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

Cite this

Kinetic feasibility of nitroxyl reduction by physiological reductants and biological implications. / Jackson, Matthew I.; Han, Tae H.; Serbulea, Laura; Dutton, Andrew; Ford, Eleonora; Miranda, Katrina M; Houk, K. N.; Wink, David A.; Fukuto, Jon M.

In: Free Radical Biology and Medicine, Vol. 47, No. 8, 15.10.2009, p. 1130-1139.

Research output: Contribution to journalArticle

Jackson, MI, Han, TH, Serbulea, L, Dutton, A, Ford, E, Miranda, KM, Houk, KN, Wink, DA & Fukuto, JM 2009, 'Kinetic feasibility of nitroxyl reduction by physiological reductants and biological implications', Free Radical Biology and Medicine, vol. 47, no. 8, pp. 1130-1139. https://doi.org/10.1016/j.freeradbiomed.2009.06.034
Jackson, Matthew I. ; Han, Tae H. ; Serbulea, Laura ; Dutton, Andrew ; Ford, Eleonora ; Miranda, Katrina M ; Houk, K. N. ; Wink, David A. ; Fukuto, Jon M. / Kinetic feasibility of nitroxyl reduction by physiological reductants and biological implications. In: Free Radical Biology and Medicine. 2009 ; Vol. 47, No. 8. pp. 1130-1139.
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