Hemoglobin Flashcards
this makes up 95% of RBC cytoplasmic contents
Hb
- O2 and CO2 transporter molecule
- also functions in maintaining acid-base balance
T or F. Free Hb has a short life span outside of the RBC
T
- carried in RBCs to protect from denaturation and loss
biconcave disc shape of RBCs purpose
provides max SA for gas exchange
Hb structure
- large, globular protein; tetramer
- 4 globin chains, each attached via iron to a heme molecule
- 2 different pairs of polypeptide chains: 2 alpha and 2 non-alpha; 8 helices per globin chain
- 4 heme groups; suspended between 2 helices
NOTE: synthesis occurs mainly in the nucleated stage of RBC maturation
requirements for Hb production
- adequate globin synthesis
- adequate synthesis of protoporphyrins (heme precursor)
- adequate iron supply
Hb structure in order
- primary: AA sequence of polypeptide
- secondary: chain arrangements in helices and non-helices
- tertiary: helices in pretzel-like configuration
- quaternary: tetramer, spherical
NOTE: AAs that are hydrophobic and heme are tucked away inside; hydrophilic = stays outside = helps Hb be soluble inside RBC cytoplasm
globin synthesis occurs between these stages
pronormoblast to reticulocyte
- forms heterodimer with another globin chain
- two heterodimers combine to form a tetramer
genes code for # different globin proteins on these chromosomes
6;6; 16 or 11
where does heme synthesis occur?
mitochondria and cytoplasm of RBC precursors
Protoporphyrin IX + iron = ?
heme
- four pyrroline rings joined by methene bridges + divalent ferrous iron (Fe 2+)
T or F. Each iron reversibly binds to one O2 molecule
T!
- if iron becomes oxidized to ferric state (Fe 3+), it can no longer bind O2
(#) of the body’s iron is bound to heme
2/3
- converts from ferric to ferrous form several times
Plasma transporter molecule
transferrin
- travels to bone marrow for incorporation into Hb ; iron carrier is transferrin
impaired production of porphyrins and heme
porphyria
- may be hereditary or acquired
- increased production, accumulation, and excretion of heme precursors
=> leads to photosensitivity, hematologic effects, hepatic effects
oxygen dissociation curve
- % O2 saturation vs pO2
- sigmoid shape
> low affinity for O2 at low tension
> high affinity for O2 at high tension - once one molecule of O2 binds, remainder of Hb molecule becomes saturated quickly: cooperativity
P50
- denotes Hb’s affinity for oxygen
- partial pressure of O2 when Hb is 50% saturated with O2 = normal (when 37C, pH 7.4) is 26-30 mmHg
More O2 required in dissociation curve
shifts right
O2 affinity decrease,
P50 increases
Less O2 required
curve shifts left
O2 affinity increases,
P50 decrease
Left shift in dissociation curve
- increased affinity for O2
- lower pressure required to reach 50% O2 saturation
- causes: decreased temp, increased pH (Bohr effect), decreased 2,3-BPG
red cell organic phosphate formed during RBC metabolism
2,3-BPG
an allosteric modifier of Hb
2,3-BPG
- deoxy = tense state
- oxy = relaxed state
this causes conformational change and modifies Hb’s affinity for O2
2,3-BPG
- enters between beta chains of hemoglobin
a shift in the oxygen dissociation curve due to a change in pH
Bohr effect
- increased CO2 = decreased pH = more need for O2 = right shift
- Hb acts as a buffer
Dyshemoglobins
methemoglobin, carboxyhemoglobin, sulfhemoglobin
methemoglobin
- reversible binding of Fe 3+
- can’t bind O2
- < 1% is normal
- acquired or hereditary causes of increased amounts
- toxic at > 50%
carboxyhemoglobin
- reversible binding of CO to heme iron
- CO affinity is 200 times greater than O2
- toxic at > 5%
sulfhemoglobin
- irreversible binding of sulfur to heme
- caused by drugs or exposure to sulfur chemicals
- toxic at > 0.5%
