Blood flow regulation by S-nitrosohemoglobin in the physiological oxygen gradient.
The binding of oxygen to heme irons in hemoglobin promotes the binding of nitric oxide (NO) to cysteinebeta93, forming S-nitrosohemoglobin. Deoxygenation is accompanied by an allosteric transition in S-nitrosohemoglobin [from the R (oxygenated) to the T (deoxygenated) structure] that releases the NO group. S-nitrosohemoglobin contracts blood vessels and decreases cerebral perfusion in the R structure and relaxes vessels to improve blood flow in the T structure. By thus sensing the physiological oxygen gradient in tissues, hemoglobin exploits conformation-associated changes in the position of cysteinebeta93 SNO to bring local blood flow into line with oxygen requirements.
Stamler
J S
JS
Department of Medicine, Duke University Medical Center, Room 321 MSRB, Box 2612, Durham, NC 27710, USA.
Jia
L
L
Eu
J P
JP
McMahon
T J
TJ
Demchenko
I T
IT
Bonaventura
J
J
Gernert
K
K
Piantadosi
C A
CA
D000818:Animals; D001794:Blood Pressure; D002560:Cerebrovascular Circulation; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D006439:Hemodynamics; D006454:Hemoglobins / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D008623:Mercaptoethanol; D008958:Models, Molecular; D009569:Nitric Oxide / Q000097:blood / Q000378:metabolism; D009603:Nitroso Compounds / Q000097:blood; D010100:Oxygen / Q000097:blood*; D010108:Oxyhemoglobins / Q000737:chemistry; D011487:Protein Conformation; D051381:Rats; D017207:Rats, Sprague-Dawley; D026403:S-Nitrosothiols
D006454:Hemoglobins; D009603:Nitroso Compounds; D010108:Oxyhemoglobins; D026403:S-Nitrosothiols; C103574:S-nitrosohemoglobin; D009569:Nitric Oxide; D008623:Mercaptoethanol; C032635:S-nitrosomercaptoethanol; C100003:deoxyhemoglobin; D003545:Cysteine; D010100:Oxygen