Reactions between nitric oxide and haemoglobin under physiological conditions

Area of Science:

• Biochemistry
• Molecular Biology
• Physiology

Background:

• Nitric oxide (NO) binding to haemoglobin (Hb) is considered high-affinity and largely irreversible.
• Existing models often overlook the allosteric state of Hb and focus on fully nitrosylated Hb.
• In vivo, Hb is only partially nitrosylated, suggesting current models may be incomplete.

Purpose of the Study:

• To investigate the influence of oxygen on the allosteric state of Hb and its interaction with NO.
• To elucidate the mechanisms of NO binding and conversion within Hb under varying oxygen conditions.
• To understand the formation of S-nitrosohaemoglobin and methaemoglobin.

Main Methods:

• Studied the conversion of nitrosylhaemoglobin in the 'tense' (deoxy) state to S-nitrosohaemoglobin in the 'relaxed' (oxy) state.
• Investigated the reaction of nitroxyl anion (NO-) liberation in the absence of oxygen.
• Quantified the yields of S-nitrosohaemoglobin and methaemoglobin as a function of the NO/Hb ratio.

Main Results:

• Oxygen actively drives the conversion of nitrosylhaemoglobin to S-nitrosohaemoglobin.
• In the absence of oxygen, nitroxyl anion is released, leading to methaemoglobin formation.
• The production of both S-nitrosohaemoglobin and methaemoglobin is dependent on the NO/Hb ratio.

Conclusions:

• Reveals novel mechanisms for NO function within the respiratory cycle.
• Provides insights into the formation of S-nitrosothiols and methaemoglobin.
• Suggests a need to re-examine NO interactions with other haem proteins, considering allosteric effects.