RBC Structure and Function Molecular Changes during Oxygenation

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

Embryonic Hemoglobin Hemoglobin Derivatives (Variants)

 Gestational age of less than 3  Hemoglobin (Methemoglobin)

months o ferrous iron is oxidized to the
o Gower-1 (72e2) ferric state (Fe2+ - Fe3+)
o Hb Portland (72y2) o Chocolate brown
o Hb Gower-2 (a2e2) discoloration of blood,
 cyanosis, and funtional
“anemia”
o Hereditary
methemoglobinemia
 Asymptomatic
cyanosis
 Hemoglobin M (Hb
M)

 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