Treatment of cyanide poisoning consists of diverting the
cyanide into the production of cyanmetHb. First, some of
the normal hemoglobin is converted to methemoglobin by
intravenous infusion of a solution of NaNC
or inhalation
of amyl nitrite. Once metHb is formed, CN- can replace
OH- at position
of the iron, since it has a higher affin-
ity of Fe3+ than does OH . CyanmetHb is no more toxic
than metHb and cells containing it can be eliminated by
normal body processes. The cyanide bound to metHb is al-
ways in equilibrium with free CN- , and this uncomplexed
cyanide is converted to thiocyanate (SCN- ; nontoxic) by
administration of thiosulfate (Chapter
Glycated Hemoglobins
Several minor varieties of hemoglobin are produced by
nonenzymatic posttranslational modification (e.g., glyca-
tion). Because these minor hemoglobins are present in
such small amounts, none is pathological.
and e-amino groups of hemoglobin form
-deoxyfructose adducts upon reaction with glu-
cose (Chapter 2). Other hexoses can give rise to similar
adducts (e.g., galactose in galactosemia; Chapter 15). The
major sites of
in vivo
glycation in order of prevalence
are /J-Vall, /1-Lys66, a-Lys61, /3-Lysl7, and a-Vall. The
adduct formed with the amino terminus of the /3 chains
is known as HbAic, which makes up about 4-6% of the
total hemoglobin in normal red blood cells. Its concen-
tration is increased in uncontrolled diabetics who have
hyperglycemia. Glycated hemoglobins are detected as
a fast-moving hemoglobin in electrophoresis at alkaline
pH. Because HbAIC accumulates within the erythrocyte
throughout the cell’s normal life span, it is used as an
indicator of the success of long-term blood glucose con-
trol in diabetics (Chapter 22). Also known are adducts
of hemoglobin with glucose-
-phosphate and fructose-
-diphosphate, which probably compete with 2,3-DPG
for binding to the
chains of deoxyhemoglobin, and a
complex between hemoglobin and glutathione, particu-
larly in older erythrocytes.
Supplemental Readings and References
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F. Grosveld, E. De Boer, N. Dillon, et al.: Dynamics of globin gene expression
and gene therapy vectors.
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C. C. W. Hsia: Respiratory function of hemoglobin.
N ew E n g la n d Jo u rn a l
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J. M. Manning, A. Dumoulin, X. Lee, et al.: Normal and abnormal protein
subunit interactions in hemoglobins.
J o u rn a l o f B io lo g ica l C h em istry
P. G. McCaffrey, D. A. Newsome, E. Fibach, et al.: Induction of y-globin
by histone deacetylase inhibitors.
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R. T. Means Jr. and S. B. Krantz: Progress in understanding the pathogenesis
of the anemia of chronic disease.
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M. Noor and E. Beutler: Acquired sulfhemoglobinemia.
W estern Jo u rn a l o f
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N. F. Olivieri: The /З-Thalassemias.
N ew E n g la n d J o u rn a l o f M ed icin e
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severely affected with sickle cell disease.
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128, 820
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L a n c e t
350, 725 (1997).
M. H. Steinberg: Management of sickle cell disease.
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340, 1021 (1999).
I. A. Tabbara: Erythropoietin.
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P. M. Tibbies and J. S. Edelsberg: Hyperbaric-oxygen therapy.
N ew E n g la n d
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334, 1642 (1996).
D. J. Weatherall and J. B. Clegg: Genetic disorders of hemoglobin.
S em in a rs
in H em a to lo g y
36, 24 (1999).
H. E. Witkowska, В. H. Lubin, Y. Beuzard, et al.: Sickle cell disease in a
patient with sickle cell trait and compound heterozygosity for hemoglobin
S and hemoglobin Quebec-Chori.
N ew E n g la n d J o u rn a l o f M ed icin e
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