674
CHAPTER 28
Hemoglobin
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
>2
or inhalation
of amyl nitrite. Once metHb is formed, CN- can replace
OH- at position
6
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
6
).
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.
Both
a-
and e-amino groups of hemoglobin form
amino-
1
-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-
6
-phosphate and fructose-
1,
6
-diphosphate, which probably compete with 2,3-DPG
for binding to the
p
chains of deoxyhemoglobin, and a
complex between hemoglobin and glutathione, particu-
larly in older erythrocytes.
Supplemental Readings and References
M. O. Arcasoy and P. G. Gallagher: Molecular diagnosis of hemo-
globinopathies and other red blood cell disorders.
S em in a rs in H e m a -
to lo g y
36, 328(1999).
G. F. Atweh, M. Sutton, L. Nassif, et al.: Sustained induction of fetal
hemoglobin by pulse butyrate therapy in sickle cell disease.
B lo o d
93,
1790(1999).
H. F. Bunn: Pathogenesis and treatment of sickle cell disease.
N ew E n g la n d
Jo u rn a l o f M ed ic in e
337, 762 (1997).
H. F. Bunn: Induction of fetal hemoglobin in sickle cell disease.
B lo o d
93,
1787 (1999).
A. Cao, R. Galanello, and M. C. Rosatelli: Genotype-phenotype correlations
in /1-thalassemias.
B lo o d R eview s
8
, 1
(1994).
M. Cazzola, F. Mercuriali, and C. Brugnara: Use of recombinant human
erythropoietin outside the setting of uremia.
B lo o d
89,4248 (1997).
D. H. K. Chui, R. Hardison, and C. Riemer: An electronic database of human
hemoglobin variants on the World Wide Web.
B lo o d
91, 2643 (1998).
S. C. Davies and L. Oni: Management of patients with sickle cell disease.
B ritish M e d ic a l J o u rn a l
315,656 (1997).
B. L. Ebert and H. F. Bunn: Regulation of the erythropoietin gene.
B lo o d
94, 1864(1999).
A. Ferster, C. Vermylen, G. Cornu, et al.: Hydroxyurea for treatment
of severe sickle cell anemia: a pediatric clinical trial.
B lo o d
88
, 1960
(1996).
J. R. Girman, Y-L. Chang, S. B. Hayward, et al.: Causes of unintentional
deaths from carbon monoxide poisonings in California.
W estern Jo u rn a l
o f M ed icin e
168, 158 (1998).
F. Grosveld, E. De Boer, N. Dillon, et al.: Dynamics of globin gene expression
and gene therapy vectors.
A n n a ls o f th e N ew York A c a d e m y o f S cien ces
550, 18(1998).
C. C. W. Hsia: Respiratory function of hemoglobin.
N ew E n g la n d Jo u rn a l
o f M ed icin e
338, 239 (1998).
E. Liakopoulou, C. A. Blau, L. Qiliang, et al.: Stimulation of fetal
hemoglobin production by short chain fatty acids.
B lo o d
86,3227 (1995).
J. A. Little, N. J. Dempsey, M. Tuchman, et al.: Metabolic persistence of
fetal hemoglobin.
B lo o d
85, 1712 (1995).
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
273,
19359(1998).
P. G. McCaffrey, D. A. Newsome, E. Fibach, et al.: Induction of y-globin
by histone deacetylase inhibitors.
B lo o d
90, 2075 (1997).
R. T. Means Jr. and S. B. Krantz: Progress in understanding the pathogenesis
of the anemia of chronic disease.
B lo o d
80, 1639 (1992).
M. Noor and E. Beutler: Acquired sulfhemoglobinemia.
W estern Jo u rn a l o f
M ed icin e
169, 386 (1998).
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
341,
99(1999).
J. P. Scott, C. A. Hillery, E. R. Brown, et al.: Hydroxyurea therapy in children
severely affected with sickle cell disease.
J o u rn a l o f P ediatrics
128, 820
(1996).
G. Serjeant: Sickle-cell disease.
L a n c e t
350, 725 (1997).
M. H. Steinberg: Management of sickle cell disease.
N ew E n g la n d Jo u rn a l
o f M ed icin e
340, 1021 (1999).
I. A. Tabbara: Erythropoietin.
A rc h iv es o f In te rn a l M ed icin e
153,298 (1993).
P. M. Tibbies and J. S. Edelsberg: Hyperbaric-oxygen therapy.
N ew E n g la n d
J o u rn a l o f M ed icin e
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
325,
1150(1991).
