Lecture 13 Hemoglobin Structure Flashcards
Hemoglobin Structure
Four heme and 2 alpha and beta globin chains
Primary structure of globin
amino acid sequence
Secondary structure of globin
helical and non-helical segments
Tertiary structure of globin
pretzel-like helical configuration with incorporation of heme group
Quaternary structure of globin
complete Hgb molecule
Adult Hgb concentrations
HgbA1: 97%, HgbA2: 2.5%, HgbF: <1%
Portland hemoglobin
2 zeta, 2 gamma, embryonic
Gower 1
2 zeta, 2 epsilon, embryonic
Gower 2
2 alpha, 2 epsilon, embryonic
HgbF
2 alpha, 2 gamma, newborn and adult
HgbA1
2 alpha, 2 beta, newborn and adult
HgbA2
2 alpha, 2 delta, newborn and adult
Newborn Hgb Concentrations
HgbF: 80%, HgbA1: 20%, HgbA2: <0.5%
Tense hemoglobin
Hgb without oxygen bound to it
Relaxed homglobin
Hgb with oxygen bound to it
of oxygens Hgb can bind
4
O2 Dissociation Curve (Normal)
PO2 = 27mmHg, 50% O2 saturation, P50: amount of O2 needed to saturate 50% of Hgb
O2 dissociation curve (shift to left)
P50 < 27mmHg, higher O2 affinity
O2 dissociation curve (shift to right)
P50 > 27 mmHg, lower O2 affinity
2,3-BPG
bound to tense hemoglobin (unable to transport O2), unbinds when hemoglobin relaxed
Causes of shift to left
- low body temp
- decreased pC02
- depleted 2,3-BPG
- increased pH
- abnormal HgB with high affinity such as HgbF
Causes of shift to the right
- increased body temp
- elevated pCO2
- increased 2,3-BPG levels
- decreased pH
- altitude
- hypoxia from heart failure, lung disease, anemia
- abnormal Hgb with decreased O2 affinity
Myoglobin
- heme found in cardiac and skeletal muscle
- greater affinity for O2
- elevated in renal disease, heart attack, and muscle damage
Bohr effect
- change in pH in blood
Bohr effect (shift to left)
- decreased H+ ions
- increased pH
- increased O2 affinity
Bohr effect (shift to right)
increased H+ ions
decreased pH
decreased O2 affinity
Chloride shift
bicarbonate diffuses out of RBC and exchanges with Cl-
maintains proper charge within RBC
bicarbonate travels to lungs and expired
Measurement of Hemoglobin: Cyanmethemoglobin method
potassium ferricyanide combines with free Hgb to from methemoglobin
potassium cyanide combines with methemoglobin to form cyanmethemoglobin
absorbance at 540 nm measured
Measurement of Hemoglobin: Sodium lauryl sulfate method (Sysmex)
does not generate toxic wastes
SLS converts Hgb to SLS-methemoglobin
Chemically Modified Hemoglobins: Methemoglobin
Fe3+ -> cannot bind oxygen
formed by spontaneous oxidation
*brownish to bluish in color: does not revert to red upon osygen exposure
methemoglobin reductase pathway converts mthemoglobin back to hemoglobin
shift to left in dissociation curve
hypoxia and cyanosis
causes: strong oxidants (nitrites), decreased methemoglobin reductase, HgbM (inherited)
treatment: removal of causative agent, administration of ascorbic acid or methylene blue (reducing agents)
measured at peak range 620-640 nm
Chemically Modified Hemoglobins: Sulfhemoglobins
addition of hydrogen sulfide (S) atom to Hgb greenish pigment shift to right in dissociation curve retains iron in ferrous state but can't carry O2 irreversible change cyanosis treatment: prevention of offending agent measured at 620 nm
Chemically Modified Hemoglobins: Carboxyhemoglobins
CO combines with heme iron
Hgb affinity for CO 240 times greater and O2 release 10000x lower
blood is cherry red
causes: automobile exhaust, coal gas, house fires, unmaintained home heating systems
shift to left of dissociation curve
10-15%: headaches and dizziness
50-70%: coma and convulsions
80% and above: immediately fatal
treatment: remove source, administer high O2, hyperbaric O2 therapy
measured at 541 nm
