Relative role of heme nitrosylation and β-cysteine 93 nitrosation in the transport and metabolism of nitric oxide by hemoglobin in the human circulation

• DOI: 10.1073/pnas.180155397
• Publication Date: 2002-07-26T14:31:44Z
• Authors: Mark T. Gladwin; Frederick P. Ogni...; Lewis K. Pannell; James S. Nichols; Margaret E. Pease...; James H. Shelhamer; Alan N. Schechter
• Keywords: Methemoglobin; Deoxygenated Hemoglobin; Nitrosylation

To quantify the reactions of nitric oxide (NO) with hemoglobin under physiological conditions and to test models NO transport on hemoglobin, we have developed an assay measure NO-hemoglobin reaction products in normal volunteers, basal during inhalation. inhalation markedly raised total nitrosylated levels, a significant arterial-venous gradient, supporting role for delivery NO. The predominant species accounting this gradient is nitrosyl(heme)hemoglobin. breathing increases S-nitrosation beta-chain cysteine 93, however only fraction level nitrosyl(heme)hemoglobin without detectable gradient. A strong correlation between methemoglobin plasma nitrate formation was observed, suggesting that metabolism primary cause oxidation. Our results demonstrate NO-heme pathways predominate vivo, binding heme groups rapidly reversible process, S-nitrosohemoglobin probably not mechanism but may facilitate release from heme.