Enzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric control.

@article{Huang2005EnzymaticFO,
  title={Enzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric control.},
  author={Z. Huang and S. Shiva and D. Kim‐Shapiro and R. Patel and L. Ringwood and Cynthia E Irby and K. Huang and C. Ho and N. Hogg and A. Schechter and M. Gladwin},
  journal={The Journal of clinical investigation},
  year={2005},
  volume={115 8},
  pages={
          2099-107
        }
}
Hypoxic vasodilation is a fundamental, highly conserved physiological response that requires oxygen and/or pH sensing coupled to vasodilation. While this process was first characterized more than 80 years ago, the precise identity and mechanism of the oxygen sensor and mediators of vasodilation remain uncertain. In support of a possible role for hemoglobin (Hb) as a sensor and effector of hypoxic vasodilation, here we show biochemical evidence that Hb exhibits enzymatic behavior as a nitrite… Expand
The functional nitrite reductase activity of the heme-globins.
TLDR
This work has revealed that hemoglobin is an allosterically regulated nitrite reductase, such that oxygen binding increases the rate of nitrite conversion to NO, a process termed R-state catalysis, and a vital role for deoxyhemoglobin- and deoxymyoglobin-dependent nitrite reduction. Expand
Deoxymyoglobin Is a Nitrite Reductase That Generates Nitric Oxide and Regulates Mitochondrial Respiration
TLDR
The nitrite reductase activity of deoxymyoglobin is characterized, which reduces nitrite approximately 36 times faster than deoxyhemoglobin because of its lower heme redox potential, and it is demonstrated that NO generation from nitrite reduction can escape heme autocapture to regulate NO-dependent signaling. Expand
Concerted Nitric Oxide Formation and Release from the Simultaneous Reactions of Nitrite with Deoxy- and Oxyhemoglobin*
TLDR
The kinetics of hemoglobin oxidation and NO generation at a range of oxygen partial pressures are characterized and it is found that the deoxy-re reaction runs in parallel with and partially inhibits the oxy-reaction. Expand
A model for the nitric oxide producing nitrite reductase activity of hemoglobin as a function of oxygen saturation.
TLDR
An analysis of the hemoglobin nitrite reductase activity based on the Monod Wyman Changeux (MWC) allosteric model is presented and a set of equations that enabled us to express the rate constant of bimolecular reaction of nitrite with hemoglobin as a function of hemoglobin saturation are derived. Expand
Hypoxia, red blood cells, and nitrite regulate NO-dependent hypoxic vasodilation.
TLDR
Evidence that hypoxic RBCs mediate vasodilation by reducing nitrite to nitric oxide (NO) and ATP release is provided and a function for RBC hemoglobin as an allosterically and redox-regulated nitrite reductase whose "enzyme activity" couples hypoxia to increased NO-dependent blood flow is supported. Expand
Nitrite Reductase Activity of Hemoglobin S (Sickle) Provides Insight into Contributions of Heme Redox Potential Versus Ligand Affinity*
TLDR
It is found that solution phase HbS reduces nitrite to NO significantly faster than HbA, supporting the thesis that heme electronics (i.e. redox potential) contributes to the high reactivity of R-state deoxy-hemes with nitrite. Expand
Effects of T- and R-state stabilization on deoxyhemoglobin-nitrite reactions and stimulation of nitric oxide signaling.
TLDR
The results support the model of allosteric regulation of nitrite Reduction by deoxyhemoglobin and show that cross-linking hemoglobins in distinct quaternary states can generate products with increased NO yields from nitrite reduction that could be harnessed to promote NO-signaling in vivo. Expand
The new chemical biology of nitrite reactions with hemoglobin: R-state catalysis, oxidative denitrosylation, and nitrite reductase/anhydrase.
TLDR
This Account reviews three novel metal- and nitrite-catalyzed reaction pathways in the context of historical studies of nitrite and hemoglobin chemistry and attempts to place them in the biological framework of hypoxic signaling. Expand
Modulating hemoglobin nitrite reductase activity through allostery: a mathematical model.
TLDR
This model is used to analyze the effect of pH (Bohr Effect) and blood ageing on the nitrite reductase activity, showing that the fall of bisphosphoglycerate during red cell storage leads to increase NO production. Expand
An S-nitrosothiol (SNO) synthase function of hemoglobin that utilizes nitrite as a substrate.
TLDR
The data provide evidence for a physiological S-nitrosothiol synthase activity of tetrameric Hb that depends on NO-Hb micropopulations and suggest that dysfunction of this activity may contribute to the pathophysiology of cardiopulmonary and blood disorders. Expand
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TLDR
In vitro spectroscopic studies that are difficult to reconcile with suggestions that the nitrite-reductase reaction of Hb generates a heme-Fe(III)NO reservoir or significantly liberates NO are reported, showing in bioassay experiments that combinations of nitrite and deoxy-Hb--under conditions that suppress SNO-HB formation--exhibit no direct vasodilatory activity. Expand
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TLDR
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TLDR
It is suggested that nitrite represents a major bioavailable pool of NO, and a new physiological function for hemoglobin as a nitrite reductase is described, potentially contributing to hypoxic vasodilation. Expand
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TLDR
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