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796 Part VI: The Erythrocyte Chapter 50: Methemoglobinemia and Other Dyshemoglobinemias 797

Figure 50–4. Hemoglobin deoxygenation (purple)
NO + NO + 2 occurs in capillaries. Nitrite reacts with deoxyHb that is
oxidized to MetHb and NO. The NO binds to hemes of
DeoxyHb + NO – 2 MetHb + NO N O 3 deoxyHb, and also undergoes dioxygenation to form
2
N 2 2 3 3 nitrate and MetHb from oxyHb. MetHb binds nitrite to
N O O
form an adduct with some Fe(II)-NO , that is, Hb-NO.
2
SNO Hb – NO 2 + + This species reacts quickly with NO to form N O , which
SNO
2
3
Hgb – NO 2
SNO
+ NO SNO can diffuse out of the red cell forming NO and effect-
+ NO
ing vasodilation and/or forming nitrosothiols (SNOs).
N O O
N (Reproduced with permission from Basu S, et al: Catalytic
MetHb + NO 2 – MetHb – NO 2 – 2 2 3 3 generation of N203 by the concerted nitrite reductase and
MetHb – NO – 2 Hb + NO + 2 anhydrase activity of hemoglobin, Nature Chemical Biology
+
Hb – NO + NO Hb + N O 3 N O 3 2007 Dec;3(12):785-794.)
2
2
2
+
NO + NO 2
and then is reduced to NO and N O along the physiologic oxygen and nitrite inhalation. Use of cell free hemoglobin is associated with vaso-
160
3
2
pH gradient by the heme globins. 143 constriction and subsequent development of hypertension. Increased
Cell free hemoglobin and red cell microparticles formed during vascular resistance and vasoconstriction has been shown to be medi-
hemolytic conditions and long storage of red blood cells (RBCs) lead to ated mainly by the scavenging of NO because of the high affinity of free
NO scavenging 1000 times faster than regular RBCs and to insufficient hemoglobin for NO. 161,162
NO bioavailability. Stored RBCs are also stored in acidic solution that
146
also leads to a decrease in SNO-Hb levels. This has been further sub-
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gen delivery in animal models. This could explain the morbidity and
147
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