Professional Documents
Culture Documents
Hemoglobin
First oxygen binds to an alpha –
Hemoglobin Molecule
change in 3D structure
Four heme groups and four
Addition of a second oxygen to the
polypeptide chains (globin)
other alpha chain – molecular
Four polypeptide chains= 2a + 2B
structure
Heme The 2,3-DPG is expelled – increase
oxygen affinity
Four iron atoms in the ferrous state
Oxygen is added to the remaining
4 iron + protoporphyrin IX ring
beta chain
o Four pyrrole rings connected
by methane bridges into a Oxygen Dissociation
larger tetrapyrrole structure.
Oxygen Transport
1.34 mL of oxygen is bound by each
gram of hemoglobin
4 heme iron = 1 oxygen
2,3-Diphosphoglycerate
Regulates the oxygen affinity of
hemoglobin
P50 value - Amount of oxygen needed to
saturate 50% of hemoglobin. 26.52 partial
pressure
Oxygen Dissociation Curve
Sigmoid-shaped
Shift to the Right
o Indicates decreased oxygen
affinity
o P50 is higher
o Hypoxic conditions such as
altitude adaptation or anemia
o Increased amounts of
deoxyhemoglobin
Shift to the Left
o Decrease in 2,3-DPG
o Higher body temperatures
o Presence of abnormal
hemoglobins
(carboxyhemoglobin) or
high oxygen affinity
hemoglobins (HbF)
o Multiple transfusions of
stored blood where 2,3-DPG
is depleted by virtue of the
storage process
o Increased pH (alkalosis)
Hemoglobin: Biosyntheis of Hemoglobin
Iron
Most abundant transition metal in the
body
DUODENUM- reduced to ferrous
iron
Each mililiter of red blood cells
contains about 1mg of iron
2 forms of storage iron
o Ferritin- ferroportin1
o Hemosiderin
Both needs copper (hephaestin and
ceruloplasmin)
Hepcidin
o Master regulatory hormone
of systemic iron metabolism
o Liver
Heme
Hemopexin
o Plasma protein that binds
heme
Haptoglobin
o Binds hemoglobin; prevents
Ferritin urinary excretion of plasma
o Water-woluble complex of hemoglobin
ferric salt and a protein,
Globin Structure and Synthesis, Hgb
apoferritin
Variants
Hemosiderin
Globin
o Water insoluble and consists
Consist of amino acids linked
mostly of aggregates of
together to form a polypeptide chain
ferric oxyhydroxide core
Alpha chains – 141 amino acids
crystals with partially or
completely degraded protein Beta chains – 146 amino acids
shells
Transferrin
o Protein that transports iron
to the normoblasts
Hephaestin
o Transforming iron to the
ferric form to enable its
uptake by circulating
apotransferrin
Ceruloplasmin
o Also has ferroxidase activity Hemoglobin
and is involved as well in the
Three types of hemoglobin that are
release of iron from the cells
synthesized:
o Embryonic hemoglobins Hemoglobin F
o Fetal hemoglobins
Major Hb of the fetus and the
o Adult hemoglobins
newborn infant
Chromosome 11 – epsilon, beta, Lower affinity for 2,3-DPG
gamma, and delta
(a2y2)
Chromosome 16 – alpha and zeta
In aults only 3% to 5% - F cells
Reactivation of Hb F synthesis
occurs normal pregnancy and in
some disorders of erythropoiesis,
particularly chronic bone marrow
failure syndromes
Hemoglobin A
Major normal adult Hb
By 6 months of age and through
adulthood
(a2B2)
Glycosylated Hemoglobin
A1A, A1B, A1C
3% to 6% (normal persons)
6% to 12% (both IDD and NIDD)
Hemoglobin A2
(a2δ2)
1.5% to 3.5% of normal adult Hb
Increase in:
o Β-thalassemias
o Hyperthyroidism
o Megaloblastic anemia
Decrease in
o iron deficiency
o alpha thalassemia
Sulfhemoglobin (SHb)
o A mixture of oxidized,
partially denatured forms of
Hb that form during oxidative
hemolysis)
o Green hemochrome
o Cannot transport 02,
o Cannot be reduced back to
Hb
Catabolism
o Blood is mauve-lavender
o As an erythrocyte ages, the
following processes occur:
The membrane
becomes less flexible
The concentration of
cellular hemoglobin
increases
Enzyme activity,
particularly
Carboxyhemoglobin glycolysis, diminishes
o Endogenous CO produced in Extravascular Catabolism
the degradation of heme to
bilirubin
o in hemolytic anemia
o Light sensitive
o Typical, brilliant, cherry red
color
RBC Metabolism
Metabolic Activities and Catabolism Intravascular Catabolism
Erythrokinetics
o Total erythropoiesis
Refers to the total
production of
hemoglobin or red
cells
o Effective erythropoiesis
Refers to production
of hemoglobin or red
blood cells that reach
the circulation
o Ineffective erythropoiesis
Refers to production
of hemoglobin or red
blood cells that never Aging Red Blood Cell Membrane
reach the circulating
blood Plasma membrane Ca2+ (PMCA)
and glycated hemoglobin
RBC Structure
Cell Membrane and Cytoplasm Cytoplasm
Maintaining hemoglobin iron in an
active ferrous (Fe2+) state
Driving the cation pump needed to
maintain intracellular sodium iom
(Na+) and potassium ion (K+)
concentrations despite the presence
of a concentration gradient
Maintaining the sulfhydryl groups
of globins, enzymes, and membranes
in an active reduced state
Preserving the integrity of the
membrane