title: Density functional theory modeling of the proposed nitrite anhydrase function of hemoglobin in hypoxia sensing.
abstract: The role of NO and nitrite-bound methemoglobin (Hb(III)NO(2)(-)) in hypoxic signaling is highly controversial. One provoking possibility is that hemoglobin (Hb) functions as a nitrite anhydrase, producing N(2)O(3) (from nitrite) as an NO carrier. The ability of Hb to generate N(2)O(3) would provide an intriguing means of NO release from red blood cells. We have investigated this proposed new reactivity of Hb using density functional theory (DFT) calculations. For this purpose, models of the Hb/myoglobin (Mb) active site have been constructed. Our results show that the O-bound (nitrito) form of Hb/Mb(III)NO(2)(-) is essential for the formation of N(2)O(3). The formation and release of N(2)O(3) is shown to be energetically favorable by 1-3 kcal/mol, indicating that the anhydrase function of Hb/Mb is biologically feasible.
authors: Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109-1055, USA.
authors: Timothy C
authors: TC
authors: Berto
authors: Nicolai
authors: N
authors: Lehnert
mesh_terms: D002256:Carbonic Anhydrases; D020134:Catalytic Domain; D006454:Hemoglobins / Q000737:chemistry*; D006801:Humans; D000860:Hypoxia / Q000201:enzymology*; D008954:Models, Biological; D015394:Molecular Structure; D009211:Myoglobin / Q000737:chemistry*; D009572:Nitrite Reductases / Q000737:chemistry*; D011789:Quantum Theory
chemical_list: D006454:Hemoglobins; D009211:Myoglobin; D009572:Nitrite Reductases; D002256:Carbonic Anhydrases