Hemoglobin 3 11.20.12 Flashcards
What is the ratio of CO:O2 affinity in Mb and Hb?
200:1
Hb combnes 200x more strongly with CO than with Oxygen to form cherry-red compound called CARBONOXYHEMOGLOBIN (Hb + 4CO –> Hb (CO)4)
What causes the Oxyghemoglobin Dissociation curve to shift left?
Methemoglobinemia
Carbon Monoxide Intoxication
How does Hb and Mb reduce affinity of CO for the heeme
by forcing a less preferred bend mode tof bidning
- Bendt mode of binding to CO to heme- distal HIS forces CO to be at an angle to heme plane
Neverless, affinity for CO is still stronger htan O2
What is Methemoblogin (HbM)
form of Hb in which iron is in the ferric state. It is different from oxygenated Hb, (oxyhemoblgobin) , in which oxygen is united loosely with ferrous iron. Mb cannot combine with and transport O2
What % of HbM in normal adult?
1.7%
Exposure to certain drugs and oxidizing agents can increase the concentration of methemoglobin
What is the cause of Familial Methemoglobinemia?
Deficiency in the enzyme methemoglobin reductase , which uses NADH –> NAD+ to go from methebmoblobin to hemoglobin
What happens to individual when methemoglobin exceeds 10% of total Hb,
affected individual will have clinically obvious cyanosis
What are the three types of inherited disorders of the hemoglbin?
structural variants,
thalassemias,
which are characterized by reduced rate of synthesis of one or more of the globin chains
hereditary persistance of fetal hemoglobin, where fetal hemoglobin synthesis continues beyond the neonatal period
What is genetically determined HbM?
it may have a TYR substituted for the PROXIMAL HIS - Fe gets oxidized to ferric form
Prox F8 HIS –> substituted by TYR F8
Also tru for TYR subststitution for DISTAL HIS
What happens wit trace Co in air. How much HbCO? Symptoms
Trace
5% HbCO
impaired vision
0.02% CO in air
20% HbCO
headach, nausea heavy smoker (smoke is not fully combustible, red color to circulation)
0.1% CO in air
40-60% HbCO
in garage) Death (RED COLOR
What is normal HbM (%)
1.7%
What is cyanosis HbM%
10%
What is genetic HbM %
15-30%
what leads to headache, weaknes, breathlessness with HbM %
> 35%
What %HbM is death
~70%
What are the three types of inherited disorders of the hemoglbin?
structural variants,
thalassemias, which are characterized by reduced rate of synthesis of one or more of the globin chains
hereditary persistance of fetal hemoglobin, where fetal hemoglobin synthesis continues beyond the neonatal period
How many structural variants of hemoglobin exist?
More than 400 structural Hb variants
What are the types of mutations that can result in teh production of essentially normal amounts of aberrant globin chains
- single base mutation
- Elongated globin chain variants
- Shortened Globin Chains
- Nonhomologous (or unequal) crossing over which produed hybrid globin chains
What causes Single Base Substitutions?
most common structural alteration producing hemoglobin variants is the substitution of one amino acid for anotehr.
Most of the amino acid substitutions can be explained by the Change of a SINGLE BASE in a triplet codon.
What causes Elongated Globin Chain Variatns
Caused either by single base substitutions in a chain termination codon, frameshift muations, or by mutations that cause failture of cleavage of the initiator methione residue.
What causes shortened Globin Chains
These variants involve deletion of one or more intact codons
What are nonhomologous (or unequal) crossing over
they are produced by hybrid globin chains