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39 Cards in this Set
- Front
- Back
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What chromosomes encode Hb a and Hb B?
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Hb A = Ch' 16
Hb B = Ch' 11 |
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What is the makeup of:
-HbA -HbA2 -HbF |
A = a2b2 - alpha/beta
A2 = a2d2 - alpha/delta F = a2y2 - alpha/gamma |
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What ch' carries the delta and gamma genes?
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Ch' 11 - along with Beta
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What causes B-thalassemia?
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Mutations that affect chain termination, transcription activation, and RNA processing.
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What is thalassemia?
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Imbalance in concentration of alpha/beta chains.
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What causes sickle cell disease?
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-Point mutation of 6th pos on B-chain; Val replaces Glu
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What inheritence pattern is exhibited by SS disease?
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Homozygous recessive
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What DNA technology is used to identify SC mutation?
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RFLP
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Is HPFH always caused by genetic deletions/mutations?
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No; it is also seen in thalassemias.
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How are myoglobin and hb different?
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Hb exists as a heterodimer, four subunits; Myoglb exists as a monomeric protein.
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What is the function of Myoglb and Hb?
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Hb - transports oxygen
Myoglb - stores oxygen |
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What is the same in Hb and Myoglb?
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Both have protoporphyrin IX prosthetic group containing Iron.
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What form must Iron be in to bind O2?
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Ferrous; if it is oxidized to Ferric FE3+ it can't bind.
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What is Hb called when oxidized?
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Methemoglobin
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Which has a higher P50; myoglb or Hb?
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Hb - it releases its O2 much sooner than Myogbn, which prefers to wait to release O2 to working muscle where the PO2 is much lower than in veins.
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How does Hb's conformation change as it picks up O2 molecules?
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Taut -> relaxed.
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How does conformation shifting affect Hb's O2 affinity?
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It increases.
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What molecule facilitates o2 release by Hb?
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2,3-BPG
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How is the iron within Heme's protoporphyrin ring shifted when it binds O2?
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O2 binding Iron shifts the Histidine that Fe is bound to; this AXIAL LIGAND transmits the binding to the subunit.
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What is the K effect?
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The effect of an allosteric regulator binding a protein to induce a conform. change that alters its affinity for substrate.
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What is the V effect?
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The effect of an allosteric regulator binding a protein to induce a conform. change that alters its Vmax.
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What are allosteric regulators of Hb?
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DPG and CO2 and H+
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What kind of effectors are DPG , CO2, and H+?
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Negative allosteric effectors.
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What is the Bohr effect?
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The reciprocal relationship between the effectors O2 and H+
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How does O2 effect Hb?
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It causes Hb to release H+ and CO2 and instead bind O2.
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What's another name for th Bohr effect?
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Isohydric shift
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What 2 amino acid residues are responsible for the Bohr affect?
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Asp 94
His 146 |
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How does Asp 94 alter Hb?
How does His 146? |
In deoxyHb, Asp 94 is in close proximity to His 146; the neg charge on Asp favors protonation of His.
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What type of effect is this interaction between Asp/His called?
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Charge microenvironment effects.
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How does protonation in the tissues cause deoxygenation of Hb?
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The protonation of His is transfered via conformation shift to the heme ring and promotes deoxygenation. Because CO2 has high affinity, it binds Fe.
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Where is the binding site of 2-3,DPG on hemoglobin?
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In a central cavity between the Beta subunits.
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How dose 2-3,DPG bind Hb?
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By ionic bonds.
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How exactly does the genetic substitution in HbS lead to symptoms?
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Polymerization of Hb occurs when it is deoxygenated; Intracellular fibers cause sickling, clogs microvessels.
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What happens to the globin chains in sickle cell disease?
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They become sticky and polymerase due to interaction of amino acid residues.
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What 3 variables affect the degree of polymerization in HbS?
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1. Degree of deoxygenation
2. Intracel. Hb concentration 3. Amt of HbF present. |
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How does HbF affect HbS?
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Inhibits polymerization because of a Glu residue at pos. 87 of y chain; prevents a lateral contact in the sickle cell fiber.
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What 2 other abnormalities in RBCs result from the membrane deformation caused by sickling?
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1. Dysreglulation of cell vol due to Ca2+ leakage (into cell)
2. Adhesion to microvessels due to incr. surface proteins exposed. |
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What is the therapeutic affect of hydroxyurea?
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-Stimulation of HbF production
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What 2 methods are used to monitor Hb constitution?
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-RFLP
-Electrophoresis |
