Reaction of S-nitrosoglutathione with the heme group of deoxyhemoglobin. J Biol Chem 2000 Nov 24;275(47):36562-7
Date
08/18/2000Pubmed ID
10945989DOI
10.1074/jbc.M005347200Scopus ID
2-s2.0-0034711297 (requires institutional sign-in at Scopus site) 59 CitationsAbstract
The mechanism of interaction between S-nitrosoglutathione (GSNO) and hemoglobin is a crucial component of hypotheses concerning the role played by S-nitrosohemoglobin in vivo. We previously demonstrated (Patel, R. P., Hogg, N., Spencer, N. Y., Kalyanaraman, B., Matalon, S., and Darley-Usmar, V. M. (1999) J. Biol. Chem. 274, 15487-15492) that transnitrosation between oxygenated hemoglobin and GSNO is a slow, reversible process, and that the reaction between GSNO and deoxygenated hemoglobin (deoxyHb) did not conform to second order reversible kinetics. In this study we have reinvestigated this reaction and show that GSNO reacts with deoxyHb to form glutathione, nitric oxide, and ferric hemoglobin. Nitric oxide formed from this reaction is immediately autocaptured to form nitrosylated hemoglobin. GSNO reduction by deoxyHb is essentially irreversible. The kinetics of this reaction depended upon the conformation of the protein, with more rapid kinetics occurring in the high oxygen affinity state (i.e. modification of the Cysbeta-93) than in the low oxygen affinity state (i.e. treatment with inositol hexaphosphate). A more rapid reaction occurred when deoxymyoglobin was used, further supporting the observation that the kinetics of reduction are directly proportional to oxygen affinity. This observation provides a mechanism for how deoxygenation of hemoglobin/myoglobin could facilitate nitric oxide release from S-nitrosothiols and represents a potential physiological mechanism of S-nitrosothiol metabolism.
Author List
Spencer NY, Zeng H, Patel RP, Hogg NAuthor
Neil Hogg PhD Associate Dean, Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Cell LineChromatography, High Pressure Liquid
Electron Spin Resonance Spectroscopy
Ethylmaleimide
Glutathione
Heme
Hemoglobins
Humans
Luminescent Measurements
Nitric Oxide
Nitroso Compounds
Pentetic Acid
S-Nitrosoglutathione
Ultrafiltration